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2nd International Congress on Drug Therapy in HIV InfectionGlasgow, UK - 18-22 November 1994 |
Cite as: AIDS 1994, Vol. 8 (Suppl. 4);Sxx
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Oral Abstracts Abstracts 1.1 thru 18.6, Page S1 thru S18 |
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| Victor Aber Memorial Lecture Abstract 1.1, page S1 |
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| 1.1 | EIGHT YEARS OF EXPERIENCE ON A DSMB FOR HIV/AIDS TRIALS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 1.1 AIDS 1994, Vol. 8 (Suppl. 4);S1 Thomas R. Fleming Monitoring experiences from several trials will be provided to illustrate some important issues, including the nature of deliberations involved in formulating recommendations about trial continuation or termination, the unreliability of efficacy results obtained during early stages of trial monitoring, responding to early negative results, the need for long term follow-up, and the hazards of relying on surrogate or replacement endpoints for the clinical efficacy endpoints. |
| State of the Art Lecture Abstract 1.2, page S1 |
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| 1.2 | UNSOLVED PUZZLES OF HIV PATHOGENESIS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 1.2 AIDS 1994, Vol. 8 (Suppl. 4);S1 Robin A. Weiss Although we now understand a great deal about the molecular virology of human immunodeficiency viruses (HIV), precisely how HIV causes AIDS remains a mystery. |
| Virological and Immunological Monitoring Abstracts 2.1 to 3.4, pages S1 to S3 |
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| 2.1 | VIRAL RESPONSE DRIVEN ANTIRETROVIRAL THERAPY Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 2.1 AIDS 1994, Vol. 8 (Suppl. 4);S1 Thomas C. Merioan As these changes are initially only present in a small portion of the virus in the blood, and they are detectable before elevation of virus load, they could first signal the time to change therapy. A protocol based on changing drugs at the time of the 215 mutation at high CD4 + T cell levels has been started within the ACTG and could begin to answer the question as to whether or not by individualizing therapy, one can get more sustained drug action in this disease. |
| 2.2 | IMMUNOLOGICAL MARKERS OF TREATMENT EFFICACY Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 2.2 AIDS 1994, Vol. 8 (Suppl. 4);S1 Anthonv J Pinching Ultimately, however, the clinical outcome remains the only valid basis for assessing any intervention. The use of markers, however sophisticated or well-validated, is limited to the process of defining and narrowing the set of questions to be answered in trials with clinical endpoints. They cannot be seen to predict the outcome. .This remains true, however urgent the need for effective intervention. The role of markers is to assist in generating appropriate hypotheses to test with clinical end-points, to justify pursuing further investment in a particular therapy, and to guide the necessarily provisional nature of therapeutic decision-making. |
| 2.3 | CHANGES IN HIV-I RNA LEVELS MEASURED BY QUANTITATIVE PCR DURING TREATMENT WITH 3TC'™ MONOTHERAPY: CORRELATION WITH HIV-I DISEASE PROGRESSION Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 2.3 AIDS 1994, Vol. 8 (Suppl. 4);S2 C Loveday, U Ayliffe, R van Leeuwen, R Tubiana, V Kitchen, A Hill, P Collis and R Tedder Additional follow-up has occurred after the data cut-off point for this analysis and will be presented. At this time we conclude that the levels of HIV-1 fell during treatment with 3TC™, although the degree of reduction in HIV-1 was not correlated with the dose of 3TC. The level of HIV-I RNA after 12 weeks of treatment appeared to be predictive for progression to AIDS. |
| 2.4 | LONGTERM AZT THERAPY DOES NOT ALTER LYMPHOCYTE FUNCTION IN ASYMPTOMATIC HIV INFECTION Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 2.4 AIDS 1994, Vol. 8 (Suppl. 4);S2 Marc CI Lipman, EF Bowen, G Janossy, MA Johnson, M Bofill The mean duration of follow-up for AZT and placebo were 19 months and 23 months respectively (p = ns). Mean CD4 counts at study entry were 420 cells/μl and 470 cells/μl (p = ns). Mean lymphocyte performance over the study period Lt SEM) is given in the following table. |
| 2.5 | CHARACTERIZATION OF RAPID AND SLOW PROGRESSORS IN A COHORT OF HIV-INFECTED INDIVIDUALS IN MADRID. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 2.5 AIDS 1994, Vol. 8 (Suppl. 4);S2 Soriano V, Hartin R, Del Romero J, Martinez P, Valencia E, Thompson M, Gutierrez H, Bru F, Bravo R, Moreno V, Laguna F, Bernal A, Sabin M'L, Gonzalez-Lahoz J. This study supports both biphasic natural history and the suggestion that the broad range in the progression rates may be the result of several independent factors (from environment, the host, and the virus itself). Whether some of these parameters are merely an epiphenomenon of the underlying immunodeficiency or indicates an active role of them in the pathogenesis of the immune deficit associated with AIDS needs to be elucidated. Recent infection with more virulent HIV strains, e.g. required from subjects ongoing antiretroviral therapy or in late stages of disease, seems to be associated with the poorer prognosis in this cohort. |
| 2.6 | DISTINCT CHANGES IN HIV-1 RNA VERSUS P24 IN SERUM DURING SHORT-TERM ZIDOVUDINE THERAPY IN ASYMPTOMATIC INDIVIDUALS WITH AND WITHOUT PROGRESSION TO AIDS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 2.6 AIDS 1994, Vol. 8 (Suppl. 4);S2 S. Jurriaans, G.J. Weverling, J. Goudsmit, J. Boogaard, M. Brok, D. van Strijp, M. Koot and B. van Gemen Our data indicate that HIV-1, RNA quantification is a superior way to evaluate antiviral efficacy using disease progression as end-point. compared to p24 antigen quantification. |
| 3.1 | WHICH ANTIVIRAL AND WHEN? Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 3.1 AIDS 1994, Vol. 8 (Suppl. 4);S3 M. Sande I would not currently recommend early combination therapy. Hopefully, new therapies or therapeutic strategies will soon become available that will have a more significant impact on slowing progression, if not eradicating this infection. |
| 3.2 | HIV DRUG RESISTANCE Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 3.2 AIDS 1994, Vol. 8 (Suppl. 4);S3 Douglas D. Richman, M.D Numerous mutations have been identified in the protease gene, each antiviral compound selecting for certain mutations. The role of this resistance in therapeutic activity may be a critical issue in the development of protease inhibitors. |
| 3.3 | CD4 RISES DURING ANTI-HIV TREATMENT: STATISTICAL ARTEFACT? Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 3.3 AIDS 1994, Vol. 8 (Suppl. 4);S3 Andrew M Hill Reported trials with other nucleoside analogues have often been analysed with screening CD4 counts included in the determination of the baseline count. If a similar non-treatment related rise in CD4 occurred between screening and baseline in these studies, the magnitude and duration of the CD4 responses observed may have been over-estimated by an artificial lowering of the true baseline value. The results also have implications for the use of CD4 counts in decisions on the initiation of antiretroviral treatment. |
| 3.4 | TRANSMISSION OF 215 MUTANTS IN PRIMARY HIV INFECTION AND ANALYSIS AFTER 6 MONTHS OF ZIDOVUDINE Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 3.4 AIDS 1994, Vol. 8 (Suppl. 4);S3 L. Perrin*, S. Yerly*, A. Rakik*, S. Kinloch* and B. Hirschel # These data suggest that, in the last 3 years, transmission of ZDV resistant isolates in Geneva occurred in around 10% of newly HIV infected patients. |
| Viral Resistance Abstracts 5.1 to 5.7, pages S4 to S5 |
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| 5.1 | THE INFLUENCE OF COMBINATION THERAPY ON HIV-1 VIRAL LOAD AND DRUG RESISTANCE Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 5.1 AIDS 1994, Vol. 8 (Suppl. 4);S4 BA Larder The combinations could be ranked according to viral load reductions: AZT+3TC being the most pronounced (mean log reduction of 1.36 at week 12 and 1.25 at week 24) and AZT+ddl the least (mean log reduction of 0.67 at week 12 and 0.59 at week 24): Given the observed viral load changes, the results of larger clinical end-point trials assessing combinations will be of considerable interest. |
| 5.2 | THE PREDICTION OF CLINICAL EFFECT AND RATE OF RESISTANCE DEVELOPMENT FROM CELL CULTURE AND ANIMAL EXPERIMENTS WITH ANTI-HIV DRUGS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 5.2 AIDS 1994, Vol. 8 (Suppl. 4);S4 Bo Öberg1,2, Disa Bottiger2 and Lotta Yrang1 Infection of cynomolgus monkeys with SIV and HIV-2 give infections very similar to that at HIV-1 in humans and in the case of SIV a similar pathogenesis. The antiviral effect of AZT, ddI, ddC, d4T, PFA, FLT and other compounds have been evaluated in SIV and HIV-2-infected monkeys. There is a better correspondence between the antiviral effects in monkeys and man than between the effects in cell cultures and man. By a combination of cell culture assays determining the rate of resistance development and efficacy studies in SIV and HIV-2-infected monkeys it appears possible today to make good predictions on clinical antiviral effect and risk for resistance development of anti-HIV drugs. |
| 5.3 | SEXUAL TRANSMISSION OF ZIDOYUDINE RESISTANT HIV-1 Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 5.3 AIDS 1994, Vol. 8 (Suppl. 4);S4 David A.Cooper1, 2, A. Irnrie1,and the Sydney Primary HIV In one seroconverter, drug-resistant virus did not persist for more than 3 months following transmission, despite limited ZDV therapy for symptoms of PHI. 12 months after seroconversion this patient is clinically well, with category A I HIV disease. The long term clinical consequences of primary infection with drug resistant variants of HIV-1 remain to be determined. |
| 5.4 | MECHANISTIC STUDIES OF NUCLEOSIDE RESISTANCE INVOLVING RECOMBINANT PURIFIED HIV REVERSE TRANSCRIPTASE Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 5.4 AIDS 1994, Vol. 8 (Suppl. 4);S4 Mark A. Wainberq, Zhengxian Gu, Eric Arts, Xuguang Li and Michael Parniak This method involves the use of genomic RNA as template and tRNALLYS3 as a primer of RT activity. We found that recombinant HIV RTs containing only K65R or both the K65R and M184V mutations yielded significantly more (-) strong-stop product in the presence of ddCTP, 3TCTP and ddATP than did wild-type HIV-1 RT. |
| 5.5 | AZT RESISTANCE AND DISEASE PROGRESSION IN THE CONCORDE TRIAL Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 5.5 AIDS 1994, Vol. 8 (Suppl. 4);S5 F. Brun-Vézinet, S. Kaye*, F. Ferchal, C. Loveday*, C. Buffet-Janvresse, R. Tedder*, and the Concorde Coordinating Committee In the french case-control study high level of resistance (IC50≥1μM) was a rare event in the patients. Mutation at codon 215 was systematically associated with decrease in AZT susceptibility (IC50≥0.05μM).Single mutation at codon 70 was very common, not predictive of occurence of resistance and could be observed in pretherapy specimens. The analysis of this case control study, based on the PCR results, showed a significant association (p=0.001)between emergence of mutation at codon 215 and clinical progression. Resistant viral populations were detected at least 6-9 months before the clinical event. Statistical analyses of the correlation between AZT resistance and clinical progression, adjusted on CD4 cell counts and viral load will be presented. These results will also be extended to those of the U.K. case control study. |
| 5.6 | QUANTIFICATION OF SERUM VIRAL LOAD, RESISTANT MUTATIONS AND CLINICAL OUTCOME IN PATIENTS (MRC ALPHA TRIAL) STOPPING ZIDOVUDlNE (ZDV) AND COMMENCING DIDANOSINE (ddl) Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 5.6 AIDS 1994, Vol. 8 (Suppl. 4);S5 C Loveday, L Comber, U Ayliffe, JH Darbyshire*., A Babiker*, RS Tedder, A Valentine, A Pinching and The Alpha Coordinating Committee. Serum viral load showed a mean fall of 0.77 log10 over the study period as resistance at codon 74 increased from <2% to 45%. The acquisition of resistance at codon 74 was dose dependent. A reciprocal relationship between codon 215 and 74 was only seen if pretreatment 215 prevalence was submaximal. |
| 5.7 | CHARACTERISATION OF HIV DRUG SENSITIVITY DURING ANTIRETROVIRAL TREATMENT WITH A PROTEASE INHIBITOR (RO 31.8959 - SAQUINAVIR) ALONE OR IN COMBINATION WITH ZIDOVUDINE. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 5.7 AIDS 1994, Vol. 8 (Suppl. 4);S5 Andreoni Massimo, L. Ercoli, L Sarmati, §J. Mous, @ K. Bragman, #I. Duncan, *G. Giannini, *C. Galluzzo, *S. Vella The preliminary data regarding the pattern of reduced sensitivity to Ro 31-8959 suggest that drug resistance may not be a major problem in the management of patients with this protease inhibitor. |
| Combination Therapy Abstracts 7.1 to 7.6, pages S5 to S7 |
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| 7.1 | Presentation Withdrawn Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 7.1 AIDS 1994, Vol. 8 (Suppl. 4);S5 |
| 7.2 | EFFICACY AND TOXICITIES OF COMBINATION ANTIRETROVIRAL THERAPIES Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 7.2 AIDS 1994, Vol. 8 (Suppl. 4);S6 Margaret A. Fischl, M.D. These data would suggest the need for further evaluation of combination therapies for the treatment of all stages of HIV disease. The possibilities of combining drugs that effect different sites of HIV replication exists and include combinations of nucleoside analogues and either protease inhibitors or glycosylation inhibitors. |
| 7.3 | RESULTS OF A RANDOMIZED MULTICENTER STUDY (ISS 902) FOR THE COMPARATIVE EVALUATION OF AZT AND DDI IN PREVIOUSLY UNTREATED PATIENTS WITH MILDLY SYMPTOMATIC HIV DISEASE. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 7.3 AIDS 1994, Vol. 8 (Suppl. 4);S6 Vella Stefano, Floridia M., Seeber A., Tomino C., Sebastiani G., Fragola V., Weimer L.E., Ricciardulli D. (Laboratorio di Virologia, Istituto Superiore di Sanitá, Rome), and the Italian AZT/DDI Evaluation Group. Sample size: more than 500 patients were enrolled, with a relatively high proportion of women (28 %). Events: over 100 AIDS defining events were recorded during the study period (the trial started on September 1990). Mean follow up: about two years. Efficacy: An intention to treat approach was used to describe progression to AIDS and survival in a Kaplan-Meyer analysis. Subgroup analysis was performed according to baseline CD4 levels and clinical status. Toxicity: AZT and DDI showed similar toxicity event rates, but distinct toxicity patterns: main adverse events for AZT were due to haematological toxicity, while DDI use was associated with a higher rate of pancreatic involvement, mostly represented by asymptomatic hyperamilasemia, with low clinical pancreatitis rate. |
| 7.4 | SURVIVAL IN ZDV-EXPERIENCED PATIENTS: COMBINATION ANTIRETROVIRAL THERAPY VS. DDI/DDC MONOTHERAPY VS. CONTINUED ZDV MONOTHERAPY. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 7.4 AIDS 1994, Vol. 8 (Suppl. 4);S6 Graham NMH, Saah AJ, Park LP, Mellors JW, Detels R, Phair JP. For men with intermediate stage HIV infection who are zidovudine experienced, adding DDI or DDC as CART was associated with significantly better survival than switching to OMT with DDI or DDC or continuing with zidovudine monotherapy. Definitive clinical trials of CART are urgently needed in intermediate and early HIV infection to assess efficacy and toxicity. |
| 7.5 | COMBINATION 3TC (LAMIVUDINE) ZDV (ZIDOVUDINE) VS ZDV MONOTHERAPY IN ZDV NAÏVE HIV-1 POSITIVE PATIENTS WITH CD4 OF 100-400 CELLS/MM3 Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 7.5 AIDS 1994, Vol. 8 (Suppl. 4);S6 C. Katlama There were no significant differences between the treatment arms in incidence of Grade III/IV clinical or laboratory toxicity. 9 patients on 3TC/ZDV and 6 patients on ZDV had withdrawn from randomised treatment by week24. 3TC/ZDV appears well tolerated in this patient population and provides significant surrogate marker benefit for at least 24 weeks. Follow up data on the surrogate marker efficacy and tolerability of 3TCIZDV for 48 weeks of treatment in will be presented. |
| 7.6 | COMBINATION 3TC (LAMIVUDINE) ZDV (ZIDOVUDINE) VS ZDV MONOTHERAPY IN ZDV PRE-TREATED HIV-1 POSITIVE PATIENTS WITH CD4 OF 100-400 CELLS/MM3 Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 7.6 AIDS 1994, Vol. 8 (Suppl. 4);S7 S. Staszewski - The European Lamivudine HIV Working Group Final analysis of 24 week unblinded data on CD4 p24, ICD p24, cellular viraemia, β 2-microglobulin and neopterin and a full safety analysis will be presented. |
| Developing World Abstracts 8.1 to 8.3, page S7 |
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| 8.1 | CLINICAL RESEARCH, PROPHYLAXIS, THERAPY, AND CARE FOR HIV DISEASE IN RESOURCE-POOR COUNTRIES Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 8.1 AIDS 1994, Vol. 8 (Suppl. 4);S7 Kevin M. De Cock Better definition of overall needs for care of persons with HIV/AIDS, including nursing, psychosocial support, and terminal care is required. Attempts are required to limit the widening gap between interventions available for HIV-infected persons in different parts of the world. |
| 8.2 | CLINICAL TRIALS AND DEVELOPING COUNTRIES, ETHICAL CODNSIDERATIONS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 8.2 AIDS 1994, Vol. 8 (Suppl. 4);S7 P Phanuphak There is no easy answer to these Questions. We have to make the best out of these controversial ethical issues so that clinical trials can be immediately started in developing countries in order to benefit the country itself as well as to add important information to the global scientific knowledge. |
| 8.3 | TRAINING FOR CLINICAL MANAGEMENT IN RESOURCE POOR SETTINGS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 8.3 AIDS 1994, Vol. 8 (Suppl. 4);S7 LATIF AS Topics covered in the training course included: generalised lymphadenopathy, fever, headache, diarrhoea, weight loss, oral thrush, respiratory conditions, skin conditions and asymptomatic HIV infection, Separate modules covering the STD associated syndromes urethral discharge, genital ulcer disease, vaginal discharge, pelvic inflammatory disease, bubo, scrotal swelling and ophthalmia neonatorum. The course materials were evaluated by trainees on completing the course. |
| Virucides, Pharmacology and Haematology Abstracts 9.1 to 9.3, page S8 |
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| 9.1 | VIRUCIDAL AGENTS AGAINST HIV TRANSMISSION Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 9.1 AIDS 1994, Vol. 8 (Suppl. 4);S8 A.B.Stone The aim is to undertake the groundwork for caring out, in due course, Phase 3 prevention trials in populations at high risk of HIV infection. In order to encourage a coordinated international effort in this developing field, close links have been established with other agencies supporting work on virucides. |
| 9.2 | INTRACELLULAR PHOSPHORYLATION ANALOGUES IN VITRO AND IN VIVO OF NUCLEOSIDE Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 9.2 AIDS 1994, Vol. 8 (Suppl. 4);S8 D.J. Back, M.G. Barry A further important area of study is drug interactions at the level of phosphorylation. in vitro phosphorylation studies may give useful leads to potential drug interactions involving nucleoside analogues in the patient population. We have screened numerous drugs for interaction with ZDV and ddC phosphate formation in stimulated PBMCs and Molt 4 cells. With ZDV, marked interactions have been seen with ribavirin and doxorubicin but no interaction with acyclovir, gancyclovir, foscarnet, ketoconazole, fluconazole, itraconazole, erythromycin, rifampicin, trimethoprim or sulphamethoxazole. |
| 9.3 | THE PATHOGENESIS AND TREATMENT OF HIV-RELATED THROMBOCYTOPENIA Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 9.3 AIDS 1994, Vol. 8 (Suppl. 4);S8 Eric Oksenhendler Using a time-dependent Cox model and after adjustment on the baseline CD4 cell count no differences on AIDS progression rate and survival were observed between the 68 splenectomized and the 117 non-splenectomized patients from our cohort study with a mean follow-up of 6 years. |
| Tumors Abstracts 10.1 to 10.3, pages S8 to S9 |
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| 10.1 | EFFICACY AND SAFETY OF STEALTH® LIPOSOMAL DOXORUBICIN (DOX-SL™) IN AIDS-RELATED KAPOSI'S SARCOMA Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 10.1 AIDS 1994, Vol. 8 (Suppl. 4);S8 JSW Stewart*, F Antunes, JCC Borleffts, W Brockhaus, D Cooper, JTh Fischer, FD Goebel, M Goos, H Jablonowski, P Kern, H Knechten, M L'Age, R Luethy, BK Mandal, WN Meigel, F Milazzo, PS Mitrou, I Schedel, N Spannbrucker, MF Spittle, HJ Stellbrink 1) DOX-SL has substantial activity in AIDS-KS; 2) DOX-SL is well-tolerated, and may lack much of the toxicity of free doxorubicin; 3) Further study of DOX-SL in AIDS-KS is justified. |
| 10.2 | 407 PATIENTS (PTS) WITH AIDS-RELATED NON-HODGKIN'S LYMPHOMA (AIDS-NHL): THE EXPERIENCE OF THE GICAT (ITALIAN COOPERATIVE GROUP ON AIDS AND TUMORS) WITH EMPHASIS ON THE PROSPECTIVE TREATMENT OF 93 PTS AT A SINGLE INSTITUTION. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 10.2 AIDS 1994, Vol. 8 (Suppl. 4);S9 U. Tirelli, M. Spina, E. Vaccher, A. Carbone and D. Serraino In conclusion, we have observed a large number of peripheral AIDS-NHL, mainly with immunoblastic and Burkitt subtypes, advanced stage and B symptoms. In the prospective treatment at a single institution, intensive chemotherapy regimens were associated both to higher CR rate and higher OIs during CT and follow up, with some pts experiencing long survival and possibly cure. The potential role of bone marrow growth factors in order to decrease bone marrow toxicity and more efficacious OI prophylactic therapy are currently prospectively tested. |
| 10.3 | EPIDEMIOLOGICAL VIROLOGICAL AND CLINICO-PATHOLOGICAL DATA FROM 114 PATIENTS (PTS) WITH HODGKIN'S DISEASE AND HIV INFECTION (HD-HIV): EVIDENCE OF SIGNIFICANT RELATION TO EPSTEIN-BARR VIRUS (EBV), INCREASE OF MIXED CELLULARUTY (MC) AND LYMPHOCYTE DEPLETION (LD) SUBTYPES AND FEASIBILITY OF COMBINED TREATMENT WITH CHEMOTHERAPY(CT) AND ZIDOVUDINE Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 10.3 AIDS 1994, Vol. 8 (Suppl. 4);S9 D. Errante, U. Tirelli, D. Serraino, M. Boiocchi, A. Carbone In conclusion, in comparison to HIV-negative HD there is evidence of a significant increase of: 1) MC and LD subtypes, 2) EBV expression in tumor tissue. Moreover, there is evidence of feasibility of antiretroviral therapy and CT with a significant reduction of OI. |
| Antiretroviral Therapy Abstracts 11.1 to 11.5, pages S9 to S10 |
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| 11.1 | NEW ANTI-VIRALS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 11.1 AIDS 1994, Vol. 8 (Suppl. 4);S9 Mark A. Wainberg The HIV protease represents a highly attractive target for anti-viral chemotherapy, in spite of the fact that selection of viruses resistant to peptide inhibitors of this enzyme has been easy to achieve in culture - New generations of protease antagonists include cyclic urea compounds, against which selection for resistance may be relatively difficult to achieve. The advent of these new compounds creates grounds for renewed optimism in the treatment of HIV-associated disease. |
| 11.2 | SAFETY, PHARMACOKINETICS AND VIROLOGICAL/IMMUNOLOGICAL EFFICACY OF ABT-538, A HIV -PROTEASE INHIBITOR. A RANDOMISED, PLACEBO-CONTROLLED PHASEVII STUDY. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 11.2 AIDS 1994, Vol. 8 (Suppl. 4);S9 S.A. Danner, D.A. Cooper, F. Gudiol, J. Gonzales, J. Tor, R. Rubio, J. Valdes, J.M.Leonard. All patients in dose group I who received ABT-538 had HIV-p24 antigen declines in excess of 40% from baseline; b-DNA and p24 antigen responses were correlated (60% concordance). Many patients who received active drug in group I had CD4+ lymphocyte increases in excess of 100% over baseline during the active study period. The drug had been well tolerated during the study. Although dose group II is still blinded, these results indicate ABT-538 has potent in-vivo antiretroviral activity. Full results from both groups will be presented at the conference. |
| 11.3 | LONG TERM FOLLOW UP OF THE PHASE1/11 STUDY OF SAQUINAVIR, IN ASYMPTOMATIC OR MILDLY SYMPTOMATIC HIV INFECTION Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 11.3 AIDS 1994, Vol. 8 (Suppl. 4);S10 V. Kitchen, C. Skinner*, E. Lane**, S. Galpin*, K. Bragman+, A. Pinching*** and J. Weber*. Long term saquinavir therapy was very well tolerated in this patient population. The results of efficacy parameters will be discussed. In addition, the emergence of resistant viral mutations over the course of the study will be discussed. |
| 11.4 | A PILOT STUDY OF THE SAFETY, TOLERANCE, PHARMACOKINETICS AND PHARMACODYNAMICS OF U-8720IE IN HIV INFECTED PERSONS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 11.4 AIDS 1994, Vol. 8 (Suppl. 4);S10 AMM Been-Tiktak1, HM Vrehen1, ICC Borleffs1, I Richens2, D Aldam2, I Williams2, IVD Weller2, AM van Loon3, R van den Akker3, P Ward4 Preliminary findings indicate that: 1. U-8720IE bas an anti-HIV effect. 2. A macular papular, rash is a common adverse event. Complete results and analysis will be presented. |
| 11.5 | CLINICAL DEVELOPMENT OF HIV-1 RESISTANCE TO THE VIRAL PROTEASE INHIBITOR L-735,524 Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 11.5 AIDS 1994, Vol. 8 (Suppl. 4);S10 EA Emini, P Deutsch, WA Schleif, JH Condra These mutations alone, however, were insufficient for resistance and required complex interactions with other amino acid substitutions that occur during therapy. Following prolonged treatment with L-735,524, viral variants were isolated that exhibited cross-resistance to a panel of structurally diverse protease inhibitors. |
| Roundtable Discussion: Kaposi's sarcoma Abstracts 13.1 to 13.6, pages S10 to S12 |
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| 13.1 | PATHOGENESIS AND AETIOLOGY OF KAPOSI SARCOMA Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 13.1 AIDS 1994, Vol. 8 (Suppl. 4);S10 Robin A. Weiss Endocrine influences may also be manifest, as individual KS lesions often appear in crops on the skin. Moreover, in non-AIDS KS there is a 10:1 ratio of incidence in men to women. |
| 13.2 | THE TREATMENT OF KAPOSI'S SARCOMA WITH CYTOTOXIC AGENTS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 13.2 AIDS 1994, Vol. 8 (Suppl. 4);S11 Karen A. Gelmon In the light of the round-table discussion of other types of treatment,the chemotherapy of KS will be discussed both in terms of its indications and pitfalls. New cytotoxic agents such as paclitaxel are also under investigation and will be discussed. |
| 13.3 | INHIBITION OF ANGIOGENESIS AS A POTENTIAL THERAPEUTIC STRATEGY FOR THE TREATMENT OF AIDS-ASSOCIATED KAPOSI'S SARCOMA (KS) Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 13.3 AIDS 1994, Vol. 8 (Suppl. 4);S11 James M. Pluda, M.D., Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, USA There currently are three antiangiogenesis agents in Phase I clinical trials for patients with AIDS-associated KS: the fumagillin analogue TNP-470 (AGM-1470); the platelet α-granule product platelet factor-4 (PF4); and a sulfated polysaccharide-peptidopolyglycan derived from an Arthrobacter species bacteria cell wall (SP.PG, DS-4152). |
| 13.4 | LIPOSOMAL ANTHRACYCLINE THERAPY OF KAPOSI'S SARCOMA (KS). OVERVIEW OF PILOT AND MULTICENTER PHASE 2 TRIALS. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 13.4 AIDS 1994, Vol. 8 (Suppl. 4);S11 PROF. C. A. Presant These results indicate frequent control by LD or LA of KS in poor risk pts with KS, with good quality of life response and little toxicity. Comparative trials of liposomal and nonliposomal chemotherapy are in progress. Liposomal chemotherapy should be considered a standard treatment in pts with drug-resistant KS. |
| 13.5 | THE ROLE OF CYTOKINES AND CYTOKINE INHIBITORS IN AIDS-RELATED KAPOSI'S SARCOMA Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 13.5 AIDS 1994, Vol. 8 (Suppl. 4);S11 Mitsuyasu R.T., Miles S.A. These studies may help answer important questions on the pathogenesis of this unusual tumor in patients with HIV as well as provide potentially more effective means of treating or preventing this tumor. |
| 13.6 | KAPOSI'S SARCOMA: BIOLOGIC THERAPY WITH INTERFERONS AND RETINOIDS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 13.6 AIDS 1994, Vol. 8 (Suppl. 4);S12 S.E. Krown These results and others lend credence to the concept of KS as a cytokine-driven proliferative process whose course may be modified by biologic agents. |
| Paediatric Issues Abstracts 14.1 to 14.3, page S12 |
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| 14.1 | THE MANAGEMENT OF INFECTIONS IN CHILDREN Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 14.1 AIDS 1994, Vol. 8 (Suppl. 4);S12 Diana Gibb Approaches to therapy for, and prevention of bacterial infections in children, will also be reviewed, as will the interaction between infections, nutritional status and growth in HIV infected children. |
| 14.2 | THE PREVENTION OF VERTICAL TRANSMISSION Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 14.2 AIDS 1994, Vol. 8 (Suppl. 4);S12 Diane W. Wara, M.D. The most important advance in clinical Pediatric HIV-1 infection during the past year is the demonstration that perinatal transmission can be reduced from 25% to 8% by the administration of oral Zidovudine to HIV-1 infected women during pregnancy, intravenously during labor, and oral suspension to newborns from birth to age 6 weeks. Although this approach to decreasing perinatal transmission is expensive and is not practical for use throughout the world, the results demonstrate that transmission can be altered, probably by decreasing maternal viral burden. |
| 14.3 | CLINICAL TRIAL ISSUES IN CHILDREN Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 14.3 AIDS 1994, Vol. 8 (Suppl. 4);S12 Dott. Carlo Giaquinto Although zidovudine remains the drug of choice in children there have been no placebo-controlled trials in pediatric population and there are still doubts on when to start treatment. Recently in Europe a trial (PENTA-1) was set up aiming to compare immediate and deferred (until symptomatic disease) use of zidovudine. So far about 180 HIV infected children have been recruited in 10 countries. results from this study will be very important to gather information about the benefits and risks of early zidovudine in children. |
| Vaccines Abstracts 15.1 to 15.4, page S13 |
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| 15.1 | PROPHYLACTIC VACCINES FOR HIV; PROGRESS AND PROSPECTS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 15.1 AIDS 1994, Vol. 8 (Suppl. 4);S13 Lewellys F. Barker Current preclinical and clinical research progress suggests that, although a veccine may be possible, the R & D road will be long and tortuous, and other approaches to preventing the spread of HIV deserve very high priority at this time. |
| 15.2 | THERAPEUTIC VACCINS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 15.2 AIDS 1994, Vol. 8 (Suppl. 4);S13 Eric Sandström In phase 1 trials stabilisation or even transient rise in CD 4 cells has been observed in those immunized. So far there has not been demonstrated a substantial reduction in the viral load in the periferal circulation. In order to evaluate these data a number of phase 2/3 trials have been initiated to study the potential clinical effect of the various immunogens. |
| 15.3 | CHANGING T-CELL IMMUNITY IN HIV VACCINATION Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 15.3 AIDS 1994, Vol. 8 (Suppl. 4);S13 Wahren, B., Persson, C., Levi, M., Broliden, K., Hinkula, J., Bratt, G.* & Sandström, E.* An rgp l60 vaccine can be used safely for at least three years, with repeated immunizations. Improved specific and recall cellular and humoral reactivities can be induced even in a secondary series of immunizations. These responses are dependent on appropriate CD4 levels, which in turn appear to be stabilized by vaccination. |
| 15.4 | A PILOT PHASE II STUDY OF THE TOLERANCE AND SAFETY OF HIV pI7/p24:Ty-VLP (p24-VLP) IN ASYMPTOMATIC HIV SEROPOSITIVE SUBJECTS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 15.4 AIDS 1994, Vol. 8 (Suppl. 4);S13 Peters B.S., Cheingsong-Popov R, Donegan D, Foxall R, Patou G*, Hodgkin K*, Adams S*, Martin S**, Weber J.N. p24-VLP immunisations of 25 and 100mcg appear well-tolerated and safe in HIV infected subjects, but higher doses and larger number of subjects are required to determine if there are significant humoral or cellular responses; CD4 changes are encouraging, and extended phase II studies are now in progress. |
| Cytokines and Interferons Abstracts 16.1 to 16.2, page S14 |
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| 16.1 | CYTOKINE THERAPIES FOR HIV Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 16.1 AIDS 1994, Vol. 8 (Suppl. 4);S14 Ronald T. Mitsuyasu, MD, Director Close monitoring for toxicities and for adverse immunologic or virologic effects should be adhered to especially in the early evaluation of these compounds. The use of these compounds in conjunction with effective antiretroviral drugs may provide powerful means of both controlling HIV infection and enhancing host immunity. |
| 16.2 | PHASE I A/B TRIAL OF IMIQUIMOD, AN ORAL INTERFERON INDUCER IN ASYMPTOMATIC HIV POSITIVE INDIVIDUALS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 16.2 AIDS 1994, Vol. 8 (Suppl. 4);S14 Goldstein D1,2, Tomkinson E1, Couldwell D3,:Golding H3, Newell M1, Hertzog P4, Owens M5, Mccarville S5, Parrish S5, Harle D6, Cooper D1,3 Increases in serum IFN levels were seen at all doses except 100 mg. There were mean increases of up to 100 x baseline at the 400 mg dose but with wide variation between patients. Smaller increases were sustained throughout maintenance. Mean II, microgiobulin and neopterin levels were significantly raised compared with baseline at all doses greater than 100 mg and large increases were associated with DLT's. A statistically significant rise in CD4 count was seen (median increase 13% at week 1 malntenance and 20% at week 9). Some patients experienced elevations in TNF-a and IL-6 at their MTD, usually in the context of high serum lFN. lmiquimod appears safe and stimulates IFN and cytokine responses in this patient population. |
| Opportunistic Infections Abstracts 17.1 to 18.6, pages S14 to S18 |
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| 17.1 | THE TREATMENT AND PROPHYLAXIS OF OPPORTUNISTIC INFECTIONS. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 17.1 AIDS 1994, Vol. 8 (Suppl. 4);S14 P. Reiss This presentation will be the first in the sessions on opportunistic infections and will be followed by a series of talks which will address a number of infections in further detail. We will try to provide an overview of the state of the art concerning the treatment and prophylaxis of the most common opportunistic infections and will briefly touch upon recent advances in management of these and some less common infections. Finally, we will try to formulate some of the priorities for further research in this field. |
| 17.2 | THE EFFECT OF ACYCLOVIR COTHERAPY ON SURVIVAL IN ADVANCED HIV DISEASE. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 17.2 AIDS 1994, Vol. 8 (Suppl. 4);S14 B G Gazzard, D A Cooper, J Stevens, A R Bell and a European Australian Collaborative Group. These results are consistent with those from other studies of ACV cotherapy in advanced HIV disease. Although the causes of improved survival are not entirely clear, these findings suggest that a herpes virus may act as a cofactor accelerating HIV replication. |
| 17.3 | TREATMENT AND PREVENTION OF TOXOPLASMIC ENCEPHALITIS. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 17.3 AIDS 1994, Vol. 8 (Suppl. 4);S15 N Clumeck As toxoplasmosis occurs more often when the total CD4 count falls below 100 cells/mm³ in patients with antibodies to T.gondii, there is a clear need for a prophylactic regimen in this setting. Presently no ideal regimen can be proposed. A reduced incidence of TE has been documented in retrospective and prospective trials on PCP oral prophylaxis using Cotrimoxazole, or Dapsone/Pyrimethamine. However, discontinuation of prophylaxis because of poor tolerance remains frequent, stressing the need for better prophylactic agents. Trials are currently underway to evaluate new agents such as atovaquone. |
| 17.4 | TREATMENT AND SUPPRESSION OF CMV INFECTIONS IN HIV-INFECTED PATIENTS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 17.4 AIDS 1994, Vol. 8 (Suppl. 4);S15 J. Mills Most of these problems and controversies would evaporate if a non-toxic, orally absorbed, highly-effective drug were available for CMV infections. Unfortunately, the existing agents under development, such as HPMPC and cyclobut-G, do not appear to satisfy those requirements. New drugs for management of CMV infections in AIDS patients are urgently needed. |
| 17.5 | RESULTS FROM RECENT THERAPEUTIC TRIALS FOR OPPORTUNISTIC INFECTIONS (OIs) FROM THE UNITED STATES Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 17.5 AIDS 1994, Vol. 8 (Suppl. 4);S15 Hardy W.D., Bozzette, S., Safrin, S., Black, J., Farthing, C., Saag, M. TMP-SMX, Dap and AP equally prevented PCP and TE by intent to treat analysis; toxicity is greatest with the oral regimens. By "as treated" analysis order of efficacy appears to be TMP-SMX ≥ Dap >> AP in those patients who can tolerate oral therapy. Treatment of mild to moderate PCP is equally effective and safe with TMP-SMX, Dap/TMP or C/P, Az/Pyr is not as effective as standard therapy for TE and should be regarded as second line or salvage therapy. Flu is superior to ltra for secondary prophylaxis of CM at the doses of ltra (200 m/d) used in this study. |
| 17.6 | TUBERCULOSIS AND HIV IN NEW YORK CITY: THE DUAL EPIDEMICS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 17.6 AIDS 1994, Vol. 8 (Suppl. 4);S15 Michael L. Tapper, MD Early identification of patients, prompt institution of appropriate isolation, chemotherapy of latent and active tuberculosis, and vigilant public health monitoring are necessary to prevent similar epidemics in HIV-infected populations elsewhere even where tuberculosis prevalence now appears low. |
| 17.7 | FLUCONAZOLE RESISTANCE IN CANDIDA ALBICANS. CORRRELATION BETWEEN CLINICAL AND IN VITRO DATA IN PATIENTS WITH AIDS. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 17.7 AIDS 1994, Vol. 8 (Suppl. 4);S16 M. Ruhnke#, A. Schmidt-Westhausen*, I. Tennagen#, A. Kirsch#. Clinical appearance of OPC could be suppressed with a multidrug antifungal therapy in 10/15 patients. It may be concluded that fluconazole resistance in C. albicans is increasingly observed and strategies for the prevention of Fluconazole resistant Candida albicans infections should be developed. |
| 17.8 | AZOLE REFRACTORY ORAL CANDIDIASIS - CLINICAL AND MYCOLOGICAL FEATURES Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 17.8 AIDS 1994, Vol. 8 (Suppl. 4);S16 A Scoular, J Holton. G Ridgway, E Ross, A Mindel In conclusion, Candida strain variation increases with advancing HIV disease; this, variation ia not modified by antifungal therapy. Azole refractory oral candidiasis is assocoiated with severe immunosuppresion, a long history of both oral candidiasis and prophylaxis and with smoking. No specific strain type was associated with refractory diseases. |
| 17.9 | IMMUNOGENICITY OF BACTERIAL POLYSACCHARIDES IN CHILDREN WITH HIV INFECTION Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 17.9 AIDS 1994, Vol. 8 (Suppl. 4);S16 Gibb D1, Spoulou V1, Griffiths H2, Masters J1, Nokes L1, Misbah S2, Giacomelli A3, Pagliaro A3, Giaquinto C3, Kroll S2, Goldblatt D1 Antibody responses to polysaccharides are decreased in children with HIV and AIDS, but the majority do respond and hence should be vaccinated. Further study of this group of children to determine long-term immunogenicity of polysaccharide vaccines in children with HIV infection is continuing. |
| 18.1 | NONTUBERCULOUS MYCOBACTERIAL INFECTIONS IN HIV DISEASE. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 18.1 AIDS 1994, Vol. 8 (Suppl. 4);S16 Chaisson, Richard E. The organism is difficult to culture and is usually detected by DNA amplification. Treatment with anti-MAC drugs is probably effective. M hemophilium may cause cutaneous and disseminated disease in patients with HIV but is far less common than the other NTM. |
| 18.2 | TREATMENT OF GUT INFECTION Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 18.2 AIDS 1994, Vol. 8 (Suppl. 4);S17 BG Gazzard, MA, MD, FRCP The variable natural history of protozoal infection in HIV infected individuals makes the analysis of uncontrolled studies of therapy difficult which, for microsporidia, are enhanced by doubts about their pathogenic importance. There is no evidence that any drug can eradicate either cryptosporidium enterocytozoan bieneusi although some produce symptomatic improvement. The major cause of severe malnutrition in HIV seropositive patients is probably diarrhoea and associated anorexia: The role of enteral feeding in this group of patients remains controversial. |
| 18.3 | CHAGAS' DISEASE IN HIV INFECTION. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 18.3 AIDS 1994, Vol. 8 (Suppl. 4);S17 C.F. Ramos-Filho Since there are anedoctal reports of response to benznidazol and nifurtimox, efforts should be made to diagnose CD. A working definition for diagnosis would be, in a patient from an endemic area, the presence of compatible CNS lesions on CT scans,serological evidence of T. cruzi infection and/or demonstration of the parasite on blood or CSF, and response to appropriate therapy. |
| 18.4 | A PROSPECTIVE STUDY OF INFECTION BY MYCOBACTERIUM AVIUM/INTRACELLULARE(MAC) IN IMMUNODEFICIENT HIV POSITIVE PATIENTS. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 18.4 AIDS 1994, Vol. 8 (Suppl. 4);S17 Julander I., Hoffner SE., Källenius G., Petrini B., Östlund L. By culture MAC could only be demonstrated in pts with a severe immunodefiency. There was an apparent correlation of positive cultures to clinical symtom. Results of sputum or feacal cultures did not predict disseminated disease. |
| 18.5 | OUTCOMES AND COSTS OF SHORT- AND LONGTERM RIFABUTIN PROPHYLAXIS FOR MYCOBACTERIUM AVIUM (MAC) DISEASE IN AIDS PATIENTS IN THE UNITED KINGDOM Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 18.5 AIDS 1994, Vol. 8 (Suppl. 4);S17 KN Simpson, RL LaVallee and DA Revicki Short or long-term use of rifabutin for U.K. patients appears to be cost effective, but long-term use may improve survival substantially without increasing costs unacceptably. The cost effectiveness ratio estimated for MAC prophylaxis is comparable to that reported for PCP prophylaxis by Schulman and colleagues (£11,322 to £12,257). |
| 18.6 | UVEITIS AND RIFABUTIN Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 18.6 AIDS 1994, Vol. 8 (Suppl. 4);S18 Kelleher P, Helbert M, Anderson J, Pinching A. St Bartholomew's Hospital Medical College, London, EClA. These findings are not unexpected since CLA inhibits RIF metabolism and RIF on its own is known to cause uveitis at doses in excess of 1500mg/day. These drugs are likely to reduce morbidity and not mortality, hence toxic interactions must be avoided. A daily combination of RIF with CLA not exceeding 300mg and 1000mg, respectively, may be safe. |
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POSTERS Abstracts P1 thru P131, Page S19 TO S51 |
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| Antiviral Resistance Abstracts P1 to P8, pages S19 to S20 |
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| P1 | RESISTANCE TO SAQUINAVIR (Ro 31-8959) OCCURS DURING PATIENT TREATMENT Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P1 AIDS 1994, Vol. 8 (Suppl. 4);S19 K.J. Ives, S. Galpin, R.B. Foxall, J.Mous, K. Bragman and J.Weber. These increases in IC50 indicate that resistance to Ro 31-8959 does occur in patients and therefore it is probable that mutations take place in patient virus in response to drug therapy. Sequencing of patient virus at both time points by PCR is in progress and this should reveal which mutations are important for resistance to this protease inhibitor, in vivo. |
| P2 | LONG TERM FOLLOW-UP OF PATIENTS TREATED WITH DDI Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P2 AIDS 1994, Vol. 8 (Suppl. 4);S19 Yerly Sabine, Kaiser L., Baumberger C, Hirschel B., Perrin L. Decreased viremia after 1 month of ddI therapy is linked to delayed disease progression. 215M may be associated with lower rate of ddI response. 40% of patients developed 74M by 24 months of ddI therapy. |
| P3 | THE APPEARANCE OF DRUG RESISTANCE ASSOCIATED POINT MUTATIONS IN HIV-1 PLASMA RNA PRECEDES THEIR APPEARANCE IN PROVIRAL DNA Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P3 AIDS 1994, Vol. 8 (Suppl. 4);S19 S. Kaye, C. Loveday, E. Comber and R.S.Tedder Viral RNA sequences are generated from existing proviral DNA sequences and genomic mutations primarily arise, it is believed, during reverse transcription. It would be predicted that mutations would be acquired in the proviral DNA sequences before viral RNA. Our results show the opposite of this suggesting either that mutation is occuring during other parts of the virus life-cycle, or, more likely, proviral DNA sequences seen in PBMCs are not representative of the total HIV infected cell population and that resistance mutations are not primarily evolving in PBMCs. This hypothesis would fit with the observation of a higher level of viral activity in the lymphoid tissue compared to the peripheral blood as reported by other groups. |
| P4 | A METHOD FOR QUANTIFICATION OF GENOTYPIC DRUG RESISTANCE IN CLINICAL SAMPLES, PERFORMANCE PARAMETERS AND APPLICATION TO THERAPEUTIC MONITORING Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P4 AIDS 1994, Vol. 8 (Suppl. 4);S19 S. Kaye, C. Loveday, E. Comber and R.S. Tedder The assay fulfills the criteria needed for the monitoring of genotypic drug resistance in clinical material, is formatted to conveniently handle large numbers of samples and is easily adapted to the assay of many mutations. |
| P5 | GENOTYPIC CHARACTERISATION OF HIV-1 FROM PATIENTS AFTER PROLONGED TREATMENT WITH THE PROTEINASE INHIBITOR SAQUINAVIR Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P5 AIDS 1994, Vol. 8 (Suppl. 4);S20 I Duncan1, H Jacobsen2, M Hãnggi2, M Ott, F Brun-Vezinet3, S Vella4, J Weber5, J Mous2 Mutations which have been previously shown to lead to reduced sensitivity to proteinase inhibitor Saquinavir in vitro could also be detected in vivo after prolonged treatment with high doses of inhibitor. |
| P6 | HIV-1 MUTATION TO ESCAPE THE EFFECT OF PROTEASE-INHIBITORS IN VITRO IMPAIRED INFECTIVITY AND CYTOPATHOGENICITY. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P6 AIDS 1994, Vol. 8 (Suppl. 4);S20 Mohamed A. El-Farrash, Marcelo J. Kuroda, and Shinji Harada. HIV-1 variants that may emerge during usage of protease inhibitors in treatment of HIV-1 infected patients will be less problematic than other drug-resistant variants. |
| P7 | A PLACEBO CONTROLLED TRIAL OF AZT ALONE OR IN COMBINATION WITH DDI OR DDC: VIRAL LOAD AND DRUG RESISTANCE Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P7 AIDS 1994, Vol. 8 (Suppl. 4);S20 P.R. Harrigan, S.D. Kemp, I. Kinghorn, S. Bloor, A. Kohli, St. Clair*, BA Larder We conclude that combination therapy with AZT + ddl or AZT + ddC does not significantly delay development of AZT resistance. However, significant effects were observed on viral load and CD4+ cell numbers (the best response being the AZT + ddC group). These results may have been due to the low occurance of ddl or ddC resistance mutations in the combination groups. |
| P8 | ANTIVIRAL POTENCY OF AZT + 3TC COMBINATION THERAPY IN VIVO SUPPORTS IN VITRO VIROLOGICAL OBSERVATIONS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P8 AIDS 1994, Vol. 8 (Suppl. 4);S20 S.D. Kemp, P.R. Harrigan, I. Kinghorn, A. Kohli, & B.A. Larder The maximum mean log reduction in serum RNA was 1.8 in the combination group versus 0.7 in the AZT group. At week 24, 94% reduction in viral load was maintained in the combination group, however, only 22% reduction from baseline remained in the AZT group. The basis of these differences might relate to the relative levels of drug-resistance between the groups. This is currently under investigation. |
| Clinical Pharmacology Abstracts P9 to P20, pages S21 to S23 |
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| P9 | UNCHANGED PHARMACOKINETICS OF AZIDOTHYMIDIN (AZT) IN HIV-INFECTED HEMOPHILIACS WITH CONCOMITANT CHRONIC HEPATITIS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P9 AIDS 1994, Vol. 8 (Suppl. 4);S21 Rockstroh JK1, Hille H2, Reichel C1, Look MP1, Oldenburg J3, Brackmann HH3 The obtained pharmacokinetic parameters for AZT in HIV-infected hemophiliacs with chronic liver disease are comparable with the values obtained from HIV-positive subjects without hepatitis. Therefore HIV-infected patients suffering from chronic hepatitis do not require dose reduction of antiviral therapy with AZT. |
| P10 | VALIDATION OF ALKALINE PHOSPHATASE(AP) USED TO OUANTIFY INTRACELLULAR (IC) ZIDOVUDINE (ZDV) METABOLITES Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P10 AIDS 1994, Vol. 8 (Suppl. 4);S21 A.M. O'Donnell, V.J. Liu, S.P. Cousins, M.F. DeRemer, and G.D. Morse. ZDV RIA CR for ZDV-MP, (ZDV-DP, and ZDV-TP was 1.97%, 0.48%, and 0.59%, respectively. Buffer IF ranged from 0.2-0.5 ng/ml. No additional IF was noted using AP Type B. Type A AP IF was variable( range: 0.3- 2.4 ng/ml). All IF was subtracted from the measured assay result. Consistent 100% recovery of parent ZDV from phosphorylated metabolites was not seen. The greatest recovery of parent drug was noted for ZDV-MP (ZDV-MP > ZDV-DP > ZDV-TP). In conclusion, 1) the optimal method to recover 100% parent ZDV from its phosphorylated anabolites remains to be clarified; 2) greater variability in the RIA assay was observed at very low sample concentrations (1 ng/ml); and 3) different forms of AP may result in varying degrees of assay interference which may confuse interpretation of clinical sample results. |
| P11 | PHARMACOKINETIC EVALUATION OF DRUG INTERACTIONS BETWEEN FLUCONAZOLE AND ZIDOVUDINE IN HIV-INFECTED PATIENTS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P11 AIDS 1994, Vol. 8 (Suppl. 4);S21 Tillmann, I., Brockmeyer, N. H., Mertins, L., Goos, M. After zidovudine intake cytochrome p450 enzyme induction was observed as Indicated by an altered antipyrine clearance whereas fluconazole elimination was not accelerated suggesting independence of this substance from the above mentioned metabolic pathways. High doses of fluconazole however, as used in treatment of esophageal candidiasis, are able to inhibit the plasma elimination of antipyrine as well as zidovudine but to an extent that no clinically relevant accumulation has to be expected. |
| P12 | MEASUREMENT OF THE ANTI HIV AGENT 2', 3'-DIDEHYDRO-2' 3' DIDEOXYTHYMIDINE (D4T) BY COMPETITIVE ELISA Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P12 AIDS 1994, Vol. 8 (Suppl. 4);S21 R. Guedj, B. Ferrua, TT. Tran, JF. Quaranta, J. Kubar, C. Rotpin, R. Condom, M. Sinet, J. Durand The extrapolation of this method to another drugs and their metabolites, such as AZT, DDI, DDC, AZT-TP, DDI-TP, DDC-TP..., will be investigated. |
| P13 | DRUG INTERACTIONS WITH ZIDOVUDINE PHOSPHORYLATION IN VITRO Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P13 AIDS 1994, Vol. 8 (Suppl. 4);S22 P. Hoggard, G. Veal, M. Wild, M. Barry & D. Back. Zidovudine (3'-azido-2', 3'-dideoxythymidine; AZT; ZDV), exerts its action following intracellular metabolism to the triphosphate anabolite. Drugs co-administered with ZDV have been examined in vitro in peripheral blood mononuclear cells (PBMCs) for effects on phosphorylation. |
| P14 | ZIDOVUDINE PHOSPHORYLATION IN HIV PATIENTS AND SERONEGATIVE VOLUNTEERS. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P14 AIDS 1994, Vol. 8 (Suppl. 4);S22 M. Barry1, M. Wild1, G. Veal1, D. Back1, A; Breckenridge1, R. Fox2, N. Beeching2, F. Nye2, P. Carey3, & D. Timmins3 Intracellular Zidovudine (ZDV) phosphate metabolites (ZDV monophosphate {ZDV-MP), ZDV diphosphate {ZDV-MP} and ZDV triphosphate (ZDV-TP}) were measured in PBMC cells from 12 patients with HIV disease and 5 seronegative volunteers following oral administration of ZDV {250 mg). Blood samples were taken at 0, 1, 2, 4 and 6 h post dosing. Ethics Committee approval and patient consent was obtained for the study. |
| P15 | PHARMACOKINETICS OF ZIDOVUDINE AND DIDEOXYINOSINE ALONE AND IN COMBINATION IN CHILDREN WITH HIV INFECTION Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P15 AIDS 1994, Vol. 8 (Suppl. 4);S22 D. Gibb1, S. Ormesher2, M. Barry2, L. Nokes1, M. Seearided3, C. Giaquinto3, D. Back2 & A. Breckenridge2 There was no significant difference in the pharmacokinetics of ZDV or ddI when administered alone and in combination in the children with HIV. |
| P16 | THE PHAAMACOKINETIC5 OF FLUCONAZOLE AFTER A SINGLE INTRAVENOUS DOSE IN AIDS PATIENTS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P16 AIDS 1994, Vol. 8 (Suppl. 4);S22 A.A. Yeates, M. Ruhnke, G. Pfaff, A. Hartmann, M. Trautmann, E. Sarnow Fluconazole is an effective antimycotic triazole with high tissue penetration, low protein binding and almost exclusive renal excretion (1), AIDS is often complicated by cryptococcal meningitis or oral candidiasis and fluconazole has been shown to be a useful drug in the treatment of these two conditions in AIDS patients (2-4). We report a comparative study of the pharmacokinetics of fluconazole after a single intravenous dose in AIDS patients and in healthy subjects. |
| P17 | TREATMENT OF AIDS-RELATED SYSTEMIC MYCOSES WITH A LIPID EMULSION FORMULATION OF AMPHOTERICIN B Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P17 AIDS 1994, Vol. 8 (Suppl. 4);S23 Leake HA, Nandwani R, Appleyard MN, Hartley JPR Further prospective comparative studies are required to compare the various preparations of amphotericin B, but the lipid emulsion described above merits consideration in AIDS patients intolerant of conventional IV amphotericin B therapy. |
| P18 | ADVERSE DRUG REACTIONS IN HIV POSITIVE PATIENTS. AN IRISH PERSPECTIVE. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P18 AIDS 1994, Vol. 8 (Suppl. 4);S23 S. Keating, A. O'Leary, C. Bergin, D. Kane and F. Mulcahy. We conclude that in our in-patient population, male ST patients are more likely to experience ADRs than IVDA patients and are also more likely to experience multiple drug reactions. No such conclusion may be inferred from the female population due to the small sample size. |
| P19 | ANTIPROTOZOAL PROPHYLAXIS WITH DAPSONE AND PYRIMETHAMINE IN HIV-INFECTED PATIENTS, DRUG-MONITORING FOR EFFICACY AND COMPLIANCE CONTROL Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P19 AIDS 1994, Vol. 8 (Suppl. 4);S23 Eliaschewitsch, Julij; Padberg J.; Grünewald Th.; Ruf B. II Compliance is a crucial point in evaluating the efficacy of prophylactic regimens. Pharmacological monitoring using routine plasma level determination in clinical studies seems to be necessary to obtain valid data on the compliance and drug efficacy. |
| P20 | STEADY-STATE KINETICS OFDAPSONE, MONO-ACETYL-DAPSONE AND PYRIMETHAMINE DURING ANTIPROTOZOAL PROPHYLAXIS IN HIV-INFECTED PATIENTS. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P20 AIDS 1994, Vol. 8 (Suppl. 4);S23 Eijaschewitsch, Julij; Padberg J.; Ruf, B. II. The applied method provides a simple means for routine drug monitoring in dapsone/pyrimethamine prophylaxis. The distribution of acetylator phenotypes in HIV-patients appears to be similar to the general population. The individual concentrations of PYR and DDS show a great variability. Plasma levels of DDS depend on the acetylator phenotype present. |
| Combination/Switch Trials Abstracts P21 to P30, pages S24 to S26 |
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| P21 | POST-ZIDOVUDINE THERAPEUTIC APPROACH: A PRELIMINARY REPORT. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P21 AIDS 1994, Vol. 8 (Suppl. 4);S24 G.Penco, M.P.Crisalli, A.Torresin, ,B.Guida, G.Cassola, R.Piscopo, N.Piersantelli. On concluding, neither treatment seems to offer major benefits; nonetheless it is likely that the better tolerance in group a) pts allow a longer-term treatment. |
| P22 | COMBINED THERAPY WITH ZIDOVUDINE PLUS ALPHA INTERFERON 2B R: A CONTROLLED STUDY ON 200 ASYMPTOMATIC HIV+ I V.D.A. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P22 AIDS 1994, Vol. 8 (Suppl. 4);S24 G. Barbarini, S Lopez*, G. Strepparola**, G. Monolo***, M. Bissolati, SFA Patruno, C. Filice. AZT + α-IFN 2b recombinant therapy is more effective in negativing or in reducing p24 antigenema than AZT alone and this therapy was generally well tolerated at the administered dose. |
| P23 | ZIDOVUDINE PLUS THYMOSTIMULIN: A CONTROLLED STUDY ON 200 ASYMPTOMATIC HIV+ SUBJECTS. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P23 AIDS 1994, Vol. 8 (Suppl. 4);S24 G. Barbarini, B. Grisorio*, G. Garavelli, D. Capelli, SFA Patruno, C. Filice. Our results suggest that combined therapy with Zidovudine plus Thymostimulin is statistically more efficacious than Zidovudine alone in restoring CD4 count and improves clinically the most part of patients. |
| P24 | THE SHORT-TERM SAFETY AND LABORATORY MARKER EFFECT OF ZDV+DDI VS ZDV+DDC IN SUBJECTS WITH CD4S OF 50 TO 350/μL. A RANDOMIZED COMPARATIVE TRIAL WITH AN OPEN ARM. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P24 AIDS 1994, Vol. 8 (Suppl. 4);S24 Montaner, Julio SG; Srour L; Singer J; Cassol S; O'Shaughnessy MV; Schechter MT. Our preliminary analysis demonstrates that short term use of ZDV+ddI or ZDV+ddC is associated with a significant increase in CD4 count. Although a trend was found in favor of ZDV+ddI, this did not reach statistical significance. Short term safety profile was similar between both regimens. P24 antigen and quantitative plasma HIV-RNA PCR results are pending. |
| P25 | LONG TERM FOLLOW-UP OF A DOUBLE BLIND STUDY OF ddI vs CONTINUED AZT AMONG INDIVIDUALS WITH CD4s 200-500/mm3. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P25 AIDS 1994, Vol. 8 (Suppl. 4);S25 M Wainberg; JSG Montaner; A Rachlis; J Gill; R Beaulieu; W Schlech; C Tsoukas; MO'Shaughnessy; J Raboud; A Thome; L Smaldone; MT Schechter et al. Our results demonstrate that an early change to ddI led to a long term benefit in clinical outcomes; this remained for at least 128 weeks, over one year after the termination of the randomized portion of the study. A change to ddI also prevented the development of AZT resistance. Both medications were generally well tolerated in the context of this study. |
| P26 | SHOULD WE EMBRACE NEW DRUGS WITH OPEN ARMS? EXPERIENCE WITHIN THE COMMUNITY BASED, OPEN ARM, RANDOMIZED STUDY OF ZDV/DDI VS ZDV/DDC. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P26 AIDS 1994, Vol. 8 (Suppl. 4);S25 Montaner, J.S.G.; Srour, L.; Hogg, R. S.; Mandigo, K.; Barber, C.G.; O'Shaughnessy, M. V; Schechter, M.T., et al. Our results illustrate the challenge posed to recruitment into clinical trials by the existence of an open arm. This is despite the non-coercive, open label, community based nature of this protocol and high priority given to it by a variety of community organizations as well as by the Canadian HIV Trials Network. It is clear that an increased commitment by all will be required if we are to ensure the viability of open arms. |
| P27 | EFFICACY AND TOLERANCE OF DDI+ZDV VS. DDC+ZDV IN PATIENTS WITH RAPID PROGRESSION OF HIV INFECTION UNDER TREATMENT WITH ZDV Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P27 AIDS 1994, Vol. 8 (Suppl. 4);S25 Mauss Stefan*, Armbrecht C.*. Adams O.**, Kajala L.*, Willers R.***, Jablonowski H.* Both regimens reduced p24-antigen in the majority of patients. Clinical events tended to be less frequent in patients on ddI, but this did not reach statistical significance. DdC was better tolerated than ddI resulting in a longer time on medication. The final analysis after 12 months of enrollment of the last patient will be presented at the meeting. |
| P28 | A COMPARATIVE TRIAL BETWEEN AZT+DDI AND MAINTENANCE OF AZT OR DDI IN HIV INFECTED PATIENTS. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P28 AIDS 1994, Vol. 8 (Suppl. 4);S25 Gensollen S.*, Mars M.E.**, Bongrand M.C.*, Timon-David P.*, Gallais H.** Some authors had previously reported that a combined therapy using AZT+ddI is better than the maintenance of a monotherapy with AZT or ddI. Our study confirms this conclusion and tends to determine the appropriate timefor the switch. Actually the benefit of the association is better for a patient with AZT, when CD-4 cells count is higher than 50/mm³. For patients with ddI, the best moment to realize the change of therapy seems to be between 50 and 200 CD-4/mm³. These facts need to be confirmed by the most important trials on combined therapy ACTG 175 and Delta. |
| P29 | SAFETY AND EFFICACY OF DIDANOSINE (DDI) IN 100 HIV POSITIVE PATIENTS. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P29 AIDS 1994, Vol. 8 (Suppl. 4);S26 G. Garavelli, B. Grisorio*, R. Maserati,F. Patruno, G.Rivolta, G. Barbarini. Among enrolled patients N.25 interruped the therapy for adverse effects (diarrhea,gastric intollerance, abdominal pains, etc.).20 died. At the end 6 months of therapy we comproved an increase of CD4 cells count in 19 patients; Ag p24, always positive more than 50pg. at the beginning of therapy, was negative after 6 months of DOl subministration in 13 patients. Only 28 patients assumed DDI for 12 months, till to day; 10 of them presented an increase of CD4 cell count and 5 negative p24 antigen. |
| P30 | THE VALIDITY OF AN HIV ADAPTATION OF THE MEDICAL OUTCOMES SURVEY QUALITY OF LIFE SCALE (MOS-HIV) IN A UK POPULATION. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P30 AIDS 1994, Vol. 8 (Suppl. 4);S26 Burgess AP, Catalan J, Hooker M, Thakrar B, Darbyshire J, Babiker A & Gazzard B. Although this study provides further support for the use of the MOS-HIV scale in assessing the psychological aspects of QoL in a British HIV seropositive population, the case for the physical aspects of QoL is more complex, although there was the expected trend for people in more advanced disease stage to report poorer QoL. The follow-up of the patients in Delta will provide information on changes over time on therapy and with disease progression. |
| Haematology Abstracts P31 to P32, page S26 |
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| P31 | AN AUDIT OF BLOOD TRANSFUSION IN HUMAN IMMUNODEFICIENCY VIRUS POSITIVE PATIENTS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P31 AIDS 1994, Vol. 8 (Suppl. 4);S26 G Arthur, F Gracie, D A Hawkim, S E Barton Following this audit, the policy in our unit was changed and we are now routinely transfusing patients with haemoglobin levels < 8.0 g/dl or those with major symptoms. Blood transfusion carries risks (CMV transmission) and is a scarce and expensive resource. It was felt that in this way those patients most likely to experience significant therapeutic benefit from treatment would be better targeted. A further evaluation of this will continue to complete the audit cycle. |
| P32 | USE OF RH ANTIBODIES IN THE TREATMENT OF HIV-RELATED IMMUNTHROMBOCYTOPENIC PURPURA Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P32 AIDS 1994, Vol. 8 (Suppl. 4);S26 Andreas Kirsch, Ulrike Schneider and Markus Ruhnke We conclude that Anti- D-Therapy is an effective and safe form or treatment in HIV-related immunothrombocytopenia. |
| Interferons, Growth Factors, Cytokines, etc. Abstracts P33 to P37, pages S27 to S28 |
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| P33 | EFFICACY OF LONG-TERM TREATMENT WITH LOW-DOSE G-CSF (FILGRASTIM) IN PREVENTING SEVERE NEUTROPENIA IN AIDS PATIENTS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P33 AIDS 1994, Vol. 8 (Suppl. 4);S27 Bambiano Rosanna, Degioanni M, Valle M, Crivelli P, Bordino C, Mastinu A, and Biglino A. Long-term treatment with G-CSF, even at low, intermittent dosage seems to prevent severe ncutropenia and its pyogenic complications in leukopenic patients with AIDS taking potentially myelotoxic drugs. |
| P34 | HEMOPOIETIC GROWTH FACTORS (HGF) IN THE MANAGEMENT OF PATIENTS WITH ADVANCED STAGE HIV INFECTION Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P34 AIDS 1994, Vol. 8 (Suppl. 4);S27 Visco Comandini U, Massetti AP, Folgori F,Mastroianni CM, Fedele CG, Vullo V The treatment with HGF seems to be a valid tool in the management of patients with idiopatic and hyatrogenic neutropenia during HIV infection,. and allows antiviral therapy or chemotherapy with mieloinhibitory effects to be continued. |
| P35 | THE USE OF GRANULOCYTE-COLONY STIMULATING FACTOR (G-CSF) IN HIV SEROPOSITIVE INDIVIDUALS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P35 AIDS 1994, Vol. 8 (Suppl. 4);S27 Fisher M, Weston RJ*, Tomlinson Dr, Coker RJ, Harris JRW. An ongoing prospective study aims to determine whether this response in neutrophil number is translated into clinical benefit (i.e. reducing infection rate). |
| P36 | NITRIC OXIDE METABOLISM IN HIV-1 INFECTION Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P36 AIDS 1994, Vol. 8 (Suppl. 4);S27 Torsten Baldeweg, Suren Sooranna, Indrajit Das, Brian Gazzard and Jose Catalan This suggests that increased immune stimulation with disease severity may lead to suppressed NO metabolism. Further studies are needed to elucidate these findings. Preliminary evidence suggests that the inducible L-arginine: nitric oxide (NO) pathway may vary depending on the severity of HIV-1 infection. |
| P37 | TREATMENT OF HIV INFECTED PATIENTS WITH PENTOXIFYLLIN Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P37 AIDS 1994, Vol. 8 (Suppl. 4);S28 LL Vaira, °A Capetti, *MG Grassi, °G Rizzardini, L Cremoni, °F Milazzo PXF seems to be effective in reducing TNF and p24 Ag in HIV pts. Best results were obtained with higher doses of the drug, but tolerance seems to be poor. 400 mg tid are better tolerated by the majority of the pts who referred an increase of well being In view of the supposed pathogenetic role of TNF in HIV disease progression, in our opinion PXF maybe an adjunctive drug in treating HIV-infection. |
| Monitoring: Virus and Immune Responses Abstracts P38 to P49, pages S28 to S31 |
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| P38 | HIV-INFECTED PATIENTS HAVE CIRCULATING CYTOTOXIC T LYMPHOCYTES ANTI-PHA-STIMULATED NORMAL CD4+ LYMPHOCYTES. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P38 AIDS 1994, Vol. 8 (Suppl. 4);S28 R.García, E. Feijoó, D.Subirá, V.Acebrón, A.Bueno, A.Jurado, S.Castañón, A. del Amo, M.Fernández-Guerrero*, F.Ortíz. It has been suggested that autoimmune phenomena contribute to the depletion of CD4+ cells and the development of AIDS in HIV-infected patients, based in part on observations that some HIV-infected patients have autoantibodies against molecules expressed on uninfected lymphocytes. In the present report we investigate the presence of a cytotoxic-mediated response in HIV-infected patients against normal CD4+ cells. |
| P39 | DYSREGULATION OF ADHESION MOLECULE EXPRESSION IN HIV INFECTION - A POTENTIAL TARGET FOR IMMUNOTHERAPY Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P39 AIDS 1994, Vol. 8 (Suppl. 4);S28 T Ng, JM Parkin, L Riddell, WJW Morrow. Currently we are conducting a phase III placebo-controlled trial to evaluate the efficacy of subcutaneous IFN-γ in advanced HIV disease. Measurements of adhesion molecule expression, in particular that of LFA-3, may provide a marker for monitoring its immunomodulatory activity. |
| P40 | IMPACT OF ASSAY REPRODUCIBILITY ON QUANTITATION OF PLASMA HIV RNA: A COMPARISON BETWEEN BRANCHED DNA (bDNA) AND REVERSE TRANSCRIPTION COUPLED POLYMERASE CHAIN REACTION (RT-PCR) ASSAYS. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P40 AIDS 1994, Vol. 8 (Suppl. 4);S28 J Todd, B Hoo, R White, T Yeghiazarian, C Pachl, J Wilber and M Urdea. This study demonstrates that the bDNA assay has a high level of precision and is appropriate for measuring small changes in plasma viral RNA that can occur during the course of anti-viral therapy and/or disease progression. |
| P41 | PLASMA VIREMIA AS A SENSITIVE INDICATOR OF ANTIRETROVIRAL THERAPY Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P41 AIDS 1994, Vol. 8 (Suppl. 4);S29 Sarmati L., Ercoli L., *Giannini G., *Galluzzo C., *Vella S., Andreoni M. Mean logarithmic reciprocal titers of plasma virus decreased by week 4 of therapy. In the patients we studied, plasma viremia was a more sensitive measure of antiviral response than measurement of p24 antigen, b2-microglobulin, neopterin or CD4 cell counts. Moreover, the demonstration in 11 patients of a significant decline in plasma virus titer after treatment with only a small difference in CD4 cell-counts provides direct evidence for an antiviral effect that may be not reflected in CD4 cell number alone. |
| P42 | HIV PROTEASE INHIBITOR RO 31-8959: ABSENCE OF IMMUNOREGULATORY EFFECTS. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P42 AIDS 1994, Vol. 8 (Suppl. 4);S29 C. Goujard*, A. Dulioust**, M.G. Enouf**, C. Wallow, and J.F. Delfraissy* In conclusion, these data indicate that this protease inhibitor used at concentrations reached in the blood of treated patients has no in vitro immunoregulatory effects. In vivo effects of RO 31-8959 have to be analyzed. These results suggest that the antiretroviral efficacy of RO 31-8959 is due to direct anti-HIV activity. |
| P43 | NUCLEOSIDE ANALOGUES SUPPRESS VIRAL REPLICATION IN PATIENTS WITH HIGH VIRUS LOAD IN VITRO BUT INTERFERE WITH T-CELL BLASTOGENESIS IN EARLIER STAGES OF HIV-INFECTION Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P43 AIDS 1994, Vol. 8 (Suppl. 4);S29 Van Lunzen Jan, Schmitz J., Schmitz H., Dietrich M. AZT, ddI and ddC suppress viral replicationin CD4+ T-cells of patients with advanced HIV-infection and high viral load in in vitro but not in patients with less advanced immunodeficiency. AZT was the most potent RT-inhibitor in concentrations reflecting peak plasma levels in vitro but has a pronounced antiproliferative effect on T-cell blastogenesis of asymptomatilc patients in vitro. Our in vitro data support the findings of recent clinical trials showing a beneficial effect of nucleoside analogues in advanced HIV disease but not in earlier stages of immunodeficiency. In those patitents AZT might even have a contradictory effect by impairment of T-cell responses. |
| P44 | HIGH YIELDS OF CD4+ AND CD8+ T-LYMPHOCYTES CAN BE OBTAINED BY LYMPHOCYTAPHERESIS AND EX VIVO PROPAGATION FOR AUTOLOGOUS ADOPTIVE IMMUNOTHERAPY OF HIV-INFECTION Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P44 AIDS 1994, Vol. 8 (Suppl. 4);S29 Van Luzen Jan, Scimitz J., Dengler K., Schmitz H., Dietrich M. High yields of T-lymphocytes obtained by lymphapheresis of asymptomatic HIV-infected individuals can be cryopreserved and propagated ex vivo under strictly autologous conditions without substantial loss of proliferative capacity or enhancement of viral replication. Lymphapheresis appears to be a safe method in this patients. Our data suggests the feasibility of an immunotherapeutic approach in HIV infection by separating and preserving T-lymphocytes early in the course of the disease and autologous retransfusion after ex vivo propagation in more advanced stages of immunodeficiency. |
| P45 | CLINICAL EFFICACY AND TOLERABILITY OF DIDANOSINE (ddI) IN RELATION TO SEVERE IMMUNODEPRESSION. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P45 AIDS 1994, Vol. 8 (Suppl. 4);S30 T Bini, F Mainini, A d'Arminio Monforte, M Arosio, C Gervasoni, M Mena, M Moroni In conclusion: neither stage or CD4+ count at baseline are associated to a different efficacy of ddI. AE seem to occur more frequently in patients with severe immunodepression. |
| P46 | EVALUATION OF TWO FLOW CYTOMETERS AND OF TWO AND THREE COLOR FLUORESCENCE LABELLING: INFLUENCE ON LYMPHOCYTE SUBSETS IN HIV INFECTION AND PRACTICABILITY IN ROUTINE LABWORK Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P46 AIDS 1994, Vol. 8 (Suppl. 4);S30 Ch. Holmgren, H. Knechten, C. Ruback Result of lymphocyte phenotyping affect diagnostic proceeding, therapy and prognosis in HIV infection. We investigated factors influencing phenotyping by analysing peripheral blood from 200 HIV infected individuals with two flow Cytometers using two and three color labeled mab kits. The CD4/CD8 mab combination doesn't exclude CD8 positive NK cells leading to significantly more CD8 positive cells with FACScan/Simulset. The slighty higher percentage of NK cells with FACScan/Simulset is of minor importance for routine diagnostic and probably due to the supplemental CD56 mab in the BD kit. We found no difference for CD3, CD-4 and CD19. As CD4 still is the most important subset in HIV infection flow cytometers and mab tested are to be considered equivalent. Nevertheless a CD3/CD4 + CD3/CD8 combination should be preferred to CD4/CD8. A significantly lower percentage of lymphocytes was measured in the resistivity method compared to flow cytometry. A reason may be that acquisition is based on one parameter. The Ortho flow cytometer was superior in routine lab work due to easy handling and the three color labeling spared extra laboratory work. Unfortunately few antibodies are available in the three color labeling. |
| P47 | THE EXPRESSION OF CD4 AND CD64 RECEPTORS ON THE SURFACE OF HUMAN SPERMATOZOA AND THEIR RELATIONSHIP TO HIV TRANSMISSION. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P47 AIDS 1994, Vol. 8 (Suppl. 4);S30 1S R Sooranna, 1J R Smith, 2J Moss, 3H Abdalla, 1P J Steer This study demonstrates the presence of both CD4 and CD64 receptors on the surface of human spermatozoa and their presence suggest that HIV may enter sperm cells. These findings are consistent with the possibility of viral transmission via spermatozoa. |
| P48 | DOES URINARY NEOPTERIN PREDICT FALLING CD4 LYMPHOCYTE COUNTS? Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P48 AIDS 1994, Vol. 8 (Suppl. 4);S30 K Rogstad, L Morgan, *J Hughes* Although the median neopterin values clearly rise as CD4 counts fall below the therapeutically significant level of 200 x 106/l, there is considerable overlap with the neopterin ranges at higher CD4 counts. We conclude that urinary neopterin is not sufficiently sensitive or specific to be a reliable marker of falling CD4 lymphocyte counts in HIV infection. |
| P49 | CIGARETTE SMOKING:EFFECTS ON PERIPHERAL BLOOD CYTOLOGY AND IMMUNOGLOBULINS IN A GLASGOW COHORT OF HIV-INFECTED SUBJECTS. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P49 AIDS 1994, Vol. 8 (Suppl. 4);S31 C.McSharry, I.C.McKay, C.Lewis, E.Galloway, C.Ross, J.McMenamin* It is important to have an objective measure of smoking in HIV subjects in order to grade exposure since smoking is strongly associated with their lifestyle. The effects of smoking on CD4+ lymphocyte count and IgA levels suggest that the smoking history of HIV-positive subjects be considered when using the above variables as indicators of disease progression. |
| Nervous System Abstracts P50 to P56, pages S31 to S32 |
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| P50 | EMPIRICAL ANTIBIOTIC THERAPY FOR NEUROSYPHILIS IN HIV-1 INFECTION Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P50 AIDS 1994, Vol. 8 (Suppl. 4);S31 Rolf Malessa*, M.W. Agelink*, N. H. Brockmeyer"* The diagnosis of neurosyphilis in HIV-infected patients constitutes a diagnostic challenge, since HIV-infection itself can cause many clinical and CSF features that resemble neurosyphilis. In a prospective survey 72 (32%) out of 223 HIV-seropositive homosexuals showed reactive serum TPHA and FTA-ABS tests. |
| P51 | EFFICACY COMPARISON OF LONG-TERM AZT AND VIROSTATIC COMBINATION TREATMENT (AZT/DDI/AZT/DDC) IN HIV-1-POSITIVE PATIENTS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P51 AIDS 1994, Vol. 8 (Suppl. 4);S31 G. Arendt, H. Hefter, H. Roick, H.-J. v. Giesen, St. Maus* Obviously, there are HIV-1-positive individuals who benefit from modification of virostatic treatment, whereas others remain stable over years with one medication only. Therefore, treatment should be planned more individually using several therapy control parameters and including neurological test procedures. |
| P52 | INFLUENCE OF DDC TREATMENT ON THE PERIPHERAL NERVOUS SYSTEM (PNS) IN HIV-1-POSITIVE PATIENTS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P52 AIDS 1994, Vol. 8 (Suppl. 4);S31 H.-J. v. Giesen, H. Roick, H, Hefter, H. Jablonowski*, G. Arendt There seems to be a special vulnerability of the PNS against ddC in advanced HIV-1 disease. Further studies must clarify whether this is due to a combination of drug and virus mediated effects. Perhaps, negative ddC effects could be avoided by carefully screening the patients in advance for pre-existing PNS-deficits. |
| P53 | IS THE OUTCOME OF HIV-1-ASSOCIATED ENCEPHALOPATHY SIGNIFICANTLY INFLUENCED BY ANTIRETROVIRAL TRERTMENT? Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P53 AIDS 1994, Vol. 8 (Suppl. 4);S32 Roick H., Giesen H. J. V.,Arendt G., Hefter H., Jablonowski H.*, Freund H.-J. In summary, the outcome of HIV-1-associated encephalopathy once clinically manifest seems not to be significantly influenced by antiretroviral treatment with AZT over longer periods of time. |
| P54 | PILOT STUDY OF THE EFFICACY OF ATEVIRDINE IN AIDS DEMENTIA COMPLEX (ADC) Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P54 AIDS 1994, Vol. 8 (Suppl. 4);S32 Brew Bruce James, Dunbar N, Druen J, Freund J, Ward P Atevirdine is effective in the treatment of ADC in both the short and long term in this pilot study. Further larger studies of this or related compounds should be considered. This pilot study also highlights the utility of ADC as a clinical non-opportunistic endpoint that can be used in the assessment of the efficacy of new antiretroviral agents. |
| P55 | MALIGNANT NEUROLEPTIC SYNDROME. 4 CASES IN AN IRISH AIDS POPULATION. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P55 AIDS 1994, Vol. 8 (Suppl. 4);S32 S. Keating, A. O'Leary, C. Bergin, D. Kane and F. Mulcahy. We conclude that when a patient with HIV encephalopathy on neuroleptic therapy presents with pyrexia of unknown origin, MNS should be considered in the differential sooner rather than later. |
| P56 | MOLECULAR HOMOLOGY BETWEEN VISNA VIRUS ENVELOPE AND SCORPION VENOM, A LIGAND OF THE SODIUM CHANNEL. Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P56 AIDS 1994, Vol. 8 (Suppl. 4);S32 MKG Tran*, Dx Nguyen** Visna-CAEV virus envelope is homologous to the complete sequence of scorpion venom Centruroides Sculpturatus CsEV3, confirming the concept of the voltage gated sodium channel as the Lentivirus (including HIV1) gp110 receptor and as TACRINE's target. CAEV arthritis may be a model of systemic lupus erythematosus. A case of multiple sclerosis (Visna demyelination was ameliorated after a scorpion sting. |
| New Antivirals: Phase I; Phase II Abstracts P57 to P63, pages S33 to S34 |
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| P57 | PHASE 1 STUDY OF SINGLE INTRAVENOUS AND SUBCUTANEOUS ASCENDING DOSES OF GEM 91 IN HIV POSITIVE, ASYMPTOMATIC VOLUNTEERS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P57 AIDS 1994, Vol. 8 (Suppl. 4);S33 D. Sereni* , C. Katlama**, A. Gouyette***, M. Ré***, C. Lascoux*, R. Tubiana**, C. Toumene**** No renal, neurological, hepatic or cardiac toxicity that could directly be attributed to GEM 91 was observed at any dose level. The most frequently reported adverse event was a localized painful nodule at the site of SC injection in 6 out of 18 patients (33.3%). These nodules were resolved with no or minor treatment. No unchanged GEM 91 could be detected in urine. Plasma concentrations are being determined. In conclusion, GEM 91 is very well tolerated at doses up to 1.0 mg/kg. We have decided to continue the study at higher doses by IV administration only, in order to reach the maximally tolerated dose. |
| P58 | SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW CARBOCYCLIC 2',3'- DIDEHYDRO-2',3'-DIDEOXY AND 3'-DEOXY-2'-FLUORO PYRIMIDINE AND PURINE NUCLEOSIDES Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P58 AIDS 1994, Vol. 8 (Suppl. 4);S33 R.Guedj1, E.E.E. Suhas1, P.R.T. Frogier1, R. Condom1, S.R. Challand2, A. Kirn3, A.-M. Aubertin3 A short synthetic route to 4-hydroxymethyl eyclopent.2-enylamine was developed. Furthermore, a convenient synthesis of 4-hydroxymethyl 2-fluoro cyclopentylamine was realised. These two synthons are interesting for further condensation with different kinds of bases to yield new antiviral drugs. |
| P59 | ORAL VALACICLOVIR - INCREASED ACYCLOVIR BIOAVAILABILITY IN DIFFERENT PATIENT POPULATIONS Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P59 AIDS 1994, Vol. 8 (Suppl. 4);S33 J Soul-Lawton, *S Weller, N On, *L Wang The delivery of increased plasma acyclovir concentrations following oral valaciclovir is achieved in advanced HIV, BMT, liver disease and ESRD patients. This should enable effective oral treatment and suppression of herpes viruses including CMV in a range of patient populations. |
| P60 | LITHIUM GAMOLENATE INHIBITS HIV REPLICATION IN CHRONICALLY INFECTED H9 CELLS AND ACUTELY INFECTED PBMC Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. P60 AIDS 1994, Vol. 8 (Suppl. 4);S33 S.L. Randall, D. Kinchington, M.D, Winther*, D.F. Horrobin* and W, L. Chan Studies with PHA-activated peripheral blood mononuclear cells taken from -HIV-seronegative individuals, infected with HIV-1RF, in the presence of 20μg/ml Li-GLA, demonstrated a reduction in virus production by measurement of reverse transcriptase released into culture supernatants on days 4, 7 and 10 post infection. There was an 11-, 14- and 9-fold reduction in reverse transcriptase release respectively, compared to untreated, infected PBMCs. Our preliminary data suggest that the inhibition of virus production from acutely infected PBMCs is not due entirely to the cytotoxic effect of Li-GLA. |
| P61 | PHASE-II-STUDY OF THE HIV PROTEASE INHIBITOR (SC-52 151 CO. SEARLE) COMPARED TO ZIDOVUDINE(ZDV)FOR THE DETERMINATION OF PHARMACOKINETICS AND EFFICACY Int Cong Drug Therapy HIV 1 |