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3rd International Congress on Drug Therapy in HIV InfectionBirmingham, UK - 3-7 November 1996 |
Cite as: AIDS 1996, Vol. 10 (Suppl. 2);Sxx
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Plenary Presentations Abstracts 1.1 thru 12.3, Page S1 thru S7 |
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| Richard Kemp Memorial Lecture Abstract 1.1, page S1 |
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| 1.1 | HAS IMMUNOTHERAPY COME OF AGE Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 1.1 AIDS 1996, Vol. 10 (Suppl. 2);S1 H. C. Lane Defining the nature of the protective immune response has been a more elusive target than defining the nature of the immunological defect. While both antibodies and cytotoxic T cells specific for HIV have been utilized as therapeutic tools, neither has demonstrated evidence of altering either the laboratory of the clinical infection in a substantive way. It is hoped that with the current ability to utilize more potent antiretroviral agents even greater advances will be possible in the area of immune based therapies. |
| State of the Art Lecture Abstract 1.2, pages S1 |
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| 1.2 | OUTSTANDING ISSUES IN THE INVESTIGATION OF ANTIRETROVIRAL CHEMOTHERAPY Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 1.2 AIDS 1996, Vol. 10 (Suppl. 2);S1 Robert T Schooley The major questions that remain include how best to accomplish this, how to maximize the accompanying immune reconstitution, what implications such antiviral and immune reconstituting effects have for primary and secondary prophylactic strategies for opportunistic infections, and whether virus can be eliminated from infected individuals. |
| Antivirals (1) Abstracts 2.1 to 2.3, pages S1 to S2 |
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| 2.1 | ANTIRETROVIRAL THERAPY STATE-OF-THE-ART: REVIEW AND RECOMMENDATIONS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 2.1 AIDS 1996, Vol. 10 (Suppl. 2);S1 Steven M. Schnittman The development of clinical guidelines for HIV therapy today requires a multi-faceted approach including evaluation of controlled clinical trials with clinical endpoints, trials assessing virologic and immunologic endpoint data of all available antiretroviral drugs, as well as extensions of our understanding of the pathogenesis of HIV-1 infection. |
| 2.2 | ACUTE HIV INFECTION: CLINICAL PRESENTATION AND TREATMENT Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 2.2 AIDS 1996, Vol. 10 (Suppl. 2);S1 Hirschel B Treatment with two or three drugs is capable of suppressing viremia to undetectable levels and normalizing immunologic parameters, including the CD4-CD8 ratio after disappearance of HIV from plasma, lymph node biopsies are all also HIV-negative. Whether erradication of HIV infection is possible is still unknown; results can be expected during 1997. |
| 2.3 | CAN ANTIVIRAL THERAPY RESTORE IMMUNE FUNCTION? Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 2.3 AIDS 1996, Vol. 10 (Suppl. 2);S2 AD Kelleher1 and DA Cooper1, 2 If restoration of lost function of the adult immune system is not possible due to HIV induced deletions of T-cell repertoire then preservation of the immune system needs to be attempted and early institution of "ablative" antiviral therapy provides the opportunity. But to be effective it must be instituted early, prior to the onset of significant deficits. |
| Clinical Trials and Regulatory Issues Abstracts 3.1 to 3.4, pages S1 to S3 |
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| 3.1 | NORTH AMERICAN/EUROPEAN PERSPECTIVES ON THE LICENSING OF DRUGS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 3.1 AIDS 1996, Vol. 10 (Suppl. 2);S2 F Rotblat Regulatory concerns at present include the mechanism for licensure of different therapeutic combinations and the ability to respond speedily to new clinical studies, particularly those not carried out under company sponsorship. |
| 3.2 | HIV VACCINES - TOWARDS PHASE III Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 3.2 AIDS 1996, Vol. 10 (Suppl. 2);S2 Jonathan Weber A Phase III trial now hangs in the balance. On one hand, safe, immunogenic vaccines of questionable efficacy; on the other hand, a large trial with no guarantee of a scientifically useful result. In the past, vaccine development has been run empirically if not immunologically. The field will probably progress faster if the same precepts continue. |
| 3.3 | COMMUNITY PERSPECTIVES ON EXPANDED ACCESS TO DRUGS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 3.3 AIDS 1996, Vol. 10 (Suppl. 2);S2 Edward King The development of potent new anti-retroviral therapies has resulted in rapid changes in perceptions of the standard of care in HIV therapy. |
| 3.4 | RESEARCH IN THE POST LICENSING SITUATION Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 3.4 AIDS 1996, Vol. 10 (Suppl. 2);S3 Merigan, T.C. We need intense study of more long term combinations especially at the virologic level and better rationales are needed for moving between combinations. It is imperative in planning all such strategy trials that the right information is obtained during phase 1/2 studies regarding the pathways for escape from drug action. For example, careful studies of tissue virus, drug resistance mechanisms and long term compliance and drug metabolism are needed. |
| Antiviral Resistance Abstracts 4.1 to 4.3, page S3 |
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| 4.1 | WHAT SHOULD WE BE MONITORING IMMUNOLOGICALLY IN ANTIVIRAL TRIALS OTHER THAN CD4+ T CELL COUNTS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 4.1 AIDS 1996, Vol. 10 (Suppl. 2);S3 F. Miedema1, N. Pakker1, K. Wolthers1, M. Koot1, M. Roos1, L. Meyaard1, J. Lange2, S. Danner2 and P. Schellekens1 Using telomere length analyses we recently have obtained data that do not provide evidence for extreme CD4+ T cell turnover, which argues against exhaustion of T cell renewal in HIV infection. Taking this all together, it will be discussed what can be expected of immune restoration after anti-viral therapy. |
| 4.2 | VIRAEMIA AND RESISTANCE FROM IN VITRO TO IN VIVO Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 4.2 AIDS 1996, Vol. 10 (Suppl. 2);S3 R S Tedder, P. Balfe, S Kaye The closest correlation is seen between genomic resistance and phenotypic resistance in culture, but in spite of selective pressures of virus isolation and culture, resistance measures ex vivo, including from plasma RNA and PBMC DNA, predict closely the rescue of phenotypically-resistant virus in culture. On a population basis PMA can also define the load of resistant virus during therapy, in trial situations this may be relevant to estimating the biological impact of virus resistance of developing in vivo. Data will be presented in support of this concept. |
| 4.3 | VIRAL DIVERSITY IN THE AFTERMATH OF CHEMOTHERAPY: BIOCHEMICAL AND TISSUE CULTURE STUDIES ON ISOLATED VIRUSES Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 4.3 AIDS 1996, Vol. 10 (Suppl. 2);S3 M.A. Weinberg In most cases in which viruses were recovered, they remained sensitive to each of these drugs. However, several patients who were non-compliant in regard to use of ddl developed resistance to Nevirapine, although not to either AZT or ddI. Sequencing studies revealed the presence of mutations associated with Nevirapine resistance in these samples. The triple combination can therefore suppress both viral load and the emergence of drug resistance. However, non-compliance may lead to resistance to Nevirapine, even in cases in which viral burden remains low. |
| Opportunistic Infections Abstracts 5.1 to 7.1, pages S4 to S5 |
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| 5.1 | PCP PROBLEMS - CONTROVERSIES 1996 Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 5.1 AIDS 1996, Vol. 10 (Suppl. 2);S4 Jens D. Lundgren When failing therapy late, admission to the ICU for mechanical ventilation needs careful evaluation. Secondary prophylaxis? Is associated with improved survival, but choice of drugs is limited. In conclusion, better prophylactic and therapeutic agents, antimicrobial sensitivity testing assays, improved diagnostic ability, and more understanding of the transmission of P. carinii are urgently needed. |
| 5.2 | CYTOMEGALOVIRUS (CMV) PROPHYLAXIS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 5.2 AIDS 1996, Vol. 10 (Suppl. 2);S4 Judith Feinberg Testing of stored samples obtained prospectively in these trials by CMV DNA PCR has advanced our understanding of pathogenesis. CMV viremia at study entry is prognostic for the later development of CMV disease. Viral load testing may enable us to identify pts at highest risk, so that prophylaxis can be targeted to that group. |
| 5.3 | MULTIPLE OPPORTUNISTIC INFECTIONS PROPHYLAXIS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 5.3 AIDS 1996, Vol. 10 (Suppl. 2);S4 C. Kaduna Because of limiting factors for a large use of all these prophylaxis — tolerance, compliance, consequences on quality of life, and cost, physicians have to evaluate — on an individual patient basis the optimal prophylactic regimen to be added to antiretroviral therapy. |
| 6.1 | MYCOBACTERIUM AVIUM COMPLEX PROPHYLAXIS AND TREATMENT Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 6.1 AIDS 1996, Vol. 10 (Suppl. 2);S4 Richard E. Chaisson Alternative agents for management of relapses are urgently needed. The prospect of immunotherapy for MAC remains alluring but unrealized. Continued progress in the management of MAC will likely emerge from ongoing investigations. |
| 6-2 | PRESENTATION WITHDRAWN Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 6.2 AIDS 1996, Vol. 10 (Suppl. 2);S5 |
| 6.3 | TUBERCULOSIS IN HIV-INFECTED PERSONS IN THE LATE 1990s Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 6.3 AIDS 1996, Vol. 10 (Suppl. 2);S5 Kevin M De Cock Patients with HIV-associated tuberculosis generally respond well to treatment but suffer an increased mortality rate, which mostly results from other HIV-associated problems. Increasing evidence suggests tuberculosis adversely affects the natural history of HIV infection by causing lymphocyte activation and increased virus replication. Vigorous tuberculosis control programmes, greater emphasis on directly observed therapy, prevention of nosocomial transmission, and use of preventive therapy for HIV-infected persons at risk for tuberculosis are required. |
| 7.1 | THE CONTROL OF MULTIPLE DRUG RESISTANCE IN TUBERCULOSIS: NEW INSIGHTS AND OLD STRATEGIES FOR THE HIV EPIDEMIC Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 7.1 AIDS 1996, Vol. 10 (Suppl. 2);S5 Michael L. Tapper, MD Infection control strategies to prevent the dissemination of tuberculosis in institutional settings remain controversial in the US although nosocomial out-breaks of tuberculosis in HIV congregate settings continue to be reported despite widespread publicity about prior US outbreaks. New challenges and areas of controversy in managing dually infected HIV/TB patients include adverse drug interactions between rifampin and protease inhibitors, and the potential contribution of rifabutin for MAC prophylaxis to subsequent development of rifampin resistance in MTB. |
| Tumors Abstracts 8.1 to 8.2, page S5 |
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| 8.1 | HHV8 IN AIDS-RELATED MALIGNANCIES Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 8.1 AIDS 1996, Vol. 10 (Suppl. 2);S5 Robin A Weiss HHV8 is associated with some forms of lymphoma and with multicentric Castleman's disease in addition to KS. The HHV8 genome contains a number of potential transforming genes, including a homologue of a cellular cyclin. This viral cyclin is expressed in latent as well as lytic infection and may contribute to the proliferation and neoplasia associated with HHV8. |
| 8.2 | UPDATE ON THE TREATMENT OF KAPOSI'S SARCOMA Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 8.2 AIDS 1996, Vol. 10 (Suppl. 2);S5 R.T. Mitsuyasu Kaposi's sarcoma (KS) was one of the first recognized AIDS-defining diseases and remains a cause of considerable morbidity in many patients. Recent advances in our understanding of the pathogenesis of KS, including its association with a newly discovered KS-associated gamma DNA virus (KSHV or HHV8) and the role of HIV-induced growth factors, suggest potential new means of controlling this tumor. |
| Pharmacology Abstract 9.1, page S6 |
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| 9.1 | INTERACTIONS WITH ANTI-HIV DRUGS - AN OVERVIEW Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 9.1 AIDS 1996, Vol. 10 (Suppl. 2);S6 Alasdair Breckenridge These considerations have relevance not only for planning therapy in the individual patient, but also in designing clinical trials and in the registration of drug combinations by licensing authorities. |
| Antivirals (2) Abstract 10.1, page S6 |
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| 10.1 | STRATEGIES FOR COMBINATION THERAPY IN HIV INFECTION Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 10.1 AIDS 1996, Vol. 10 (Suppl. 2);S6 M. S. Hirsch New questions are being raised as to the best combination antiretroviral strategies to suppress or possibly eradicate HIV-I, while at the same time minimizing toxicity and cost. Concepts of 3 or 4 drug induction regimens, followed by 1 or 2 drug maintenance regimens are being explored both in virus culture systems and in the clinic, as are ideas concerning the duration of treatment necessary to eradicate potential latent reservoirs of virus. These studies will be reviewed. |
| Practical Issues, in Patient Management Abstract 11.1 to 12.3, pages S6 to S7 |
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| 11.1 | WASTING IN HIV DISEASE - PROGRESS TOWARDS RATIONAL MANAGEMENT STRATEGY Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 11.1 AIDS 1996, Vol. 10 (Suppl. 2);S6 BG Gazzard It is likely that cachectic responses are related to stimulation of the complex cytokine network and, as such, may in the future respond to immunological manipulation although, for the present, effective treatment of the underlying opportunistic infection is the most important therapy. The role of recombinant growth hormone in such patients remains to be defined. It undoubtedly can produce impressive short term gains in lean body mass but is extremely expensive. |
| 11.2 | ISSUES IN THE CLINICAL MANAGEMENT OF THE HIV-INFECTED PATIENT Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 11.2 AIDS 1996, Vol. 10 (Suppl. 2);S6 John D. Stansell, M.D. The goal of this presentation will be to identify common areas of concern and uncertainty in the clinical management of advanced HIV infected patients and to offer possible practical interventions. |
| 11.3 | COMPREHENSIVE OUTCOME ASSESSMENT: STATUS AND FUNCTIONING Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 11.3 AIDS 1996, Vol. 10 (Suppl. 2);S7 Samuel A Bozzette, M.D., Ph. D. Recently, there has been an appropriate re-focusing on the use of laboratory markers of HIV disease activity in drug development and clinical practice. However, patients, physicians, and administrators need more information to make appropriate decisions regarding available HIV therapies. The kinds of information required can be grouped into biological, clinical, functional, and economic level outcomes. |
| 12.1 | HIV DRUG RESISTANCE — AN OVERVIEW Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 12.1 AIDS 1996, Vol. 10 (Suppl. 2);S7 Douglas D. Richman The correlation of loss of antiviral drug activity with the emergence of drug resistance has been quite straightforward for the non-nucleoside reverse transcriptase inhibitors and the potent protease inhibitors. Prevention of resistance will prove central to the new chemotherapeutic paradigm of complete suppression of HIV replication with potent combination regimens. The impact upon survival of this strategy is highly likely but not yet confirmed. |
| 12.2 | DYNAMICS OF HIV AND CD4 LYMPHOCYTES Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 8.3 AIDS 1996, Vol. 10 (Suppl. 2);S7 D. Ho Presentation withdrawn |
| 12.3 | WHEN TO START, AND WITH WHAT Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 12.3 AIDS 1996, Vol. 10 (Suppl. 2);S7 G. Skowron Clinicians in daily practice are being asked to skillfully apply the abundant early, yet encouraging, data to individuals from first exposure, to seroconversion, to asymptomatic infection and more advanced disease. More rational approaches to early and aggressive treatment await a greater understanding of the pathogenesis of HIV disease and the results of additional clinical studies. |
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Oral Abstracts Abstracts OP1.1 thru OP9.2, Page S9 thru S18 |
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| OP1.1 | COMBINATION THERAPIES IN PRIMARY HIV INFECTION Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP1.1 AIDS 1996, Vol. 10 (Suppl. 2);S9 Workman, Cassy*; Downie, J**; Smith, DE***; Sutherland, D****; Michelmore, H**, Dyer W*, Shen, J*; Sullivan, J* Aggressive antiviral therapy during primary HIV infection causes a pronounced reduction in viral load. Although combination nucleoside therapy was also effective, the addition of a PI was necessary for viral load to be sustained BD. The tolerability of saquinavir makes the combination of AZT/3TC/saquinavir an attractive regimen for treatment of primary HIV infection. It remains to be determined if this reduction in viral load is sustainable and results in an improved disease free period. |
| OP1.2 | THREE AND 4-DRUG COMBINATIONS AT DIFFERENT STAGES OF HIV-1 INFECTION: INSIGHTS INTO VIRAL DYNAMICS AND IMMUNE RECONSTITUTION Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP1.2 AIDS 1996, Vol. 10 (Suppl. 2);S9 A. Lafeuillade*, C. Poggi*, G. Kaplanski**, C. Tamalet**, N. Profizi*, C. Farnarier**, S. Kaplanski**, O. Costes* Such pilot studies are designed to determine the best therapeutic regimens. However, they also allow to investigate more precisely the pathophysiologic mechanisms of the disease. |
| OP1.3 | CD4 COUNTS RETAIN THEIR PROGNOSTIC VALUE OVER PLASMA VIRAL LOAD IN INDIVIDUALS ON COMBINATION THERAPY WITH CD4 COUNTS 50 TO 350 MM3 Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP1.3 AIDS 1996, Vol. 10 (Suppl. 2);S9 Montaner JSG, Raboud JM, Rae S, Conway B, Patenaude P, O'Shaughnessy MV, Schechter MT, et al. In summary, in individuals with CD4's from 50 to 350 who receive 2 nucleoside analogs, both CD4 counts and plasma viremia are predictive in univariate models. However, CD4 counts are more predictive of progression of disease than plasma viremia in a multivariate model. Absolute values of CD4 counts and plasma viremia are predictive while changes from baseline were not. |
| SS2.1 | CLINICAL AND SURVIVAL BENEFIT OF 3TC™ IN COMBINATION WITH ZIDOVUDINE-CONTAINING REGIMENS IN HIV-1 INFECTION: INTERIM RESULTS OF THE CAESAR STUDY Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. SS2.1 AIDS 1996, Vol. 10 (Suppl. 2);S9 C.Katlama We conclude that the addition of 3TC to concurrent AZT-containing regimens significantly reduced progression to AIDS or death and increased survival significantly. Additional clinical benefit was not shown with the addition of loviride to 3TC. However, as the trial was not powered to detect this, further investigations will be perfonned to assess the effect of loviride in certain sub-groups. CAESAR was formally terminated on July 23rd 1996 at the recommendation of the DSMB. |
| SS2.2 | ABSTRACT WITHDRAWN Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. SS2.2 AIDS 1996, Vol. 10 (Suppl. 2);S9 |
| SS2.3 | MODELLING THE COST-EFFECTIVENESS OF EPIVIR™ (3TC™) / RETROVIR™ (ZIDOVUDINE) COMBINATION THERAPY IN HIV INFECTION Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. SS2.3 AIDS 1996, Vol. 10 (Suppl. 2);S10 NM Chancellor1, AM Hill2, CA Sabin3, KN Simpson4 and M Youles5 Based on an estimated RR of progression of 0.509 (95% CI 0.365-0.710), treatment with 3TC/ZDV is predicted to yield an incremental cost-effectiveness ratio of circa £6,500 per life year saved (discounted @ 6%). Extensive sensitivity analyses were performed to test the effects of varying values of input parameters on the model results. Under reasonable assumptions, the predicted cost-effectiveness of 3TC/ZDV combination therapy compares favourably with previously reported economic analyses of various HIV treatments. |
| OP2.1 | FUNCTIONAL CAPACITY OF T CELLS AND IMMUNOLOGIC RESPONSE IN NAÏVE HIV-1 PATIENTS TREATED WITH COMBINATIONS OF REVERSE TRANSCRIPTASE INHIBITORS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP2.1 AIDS 1996, Vol. 10 (Suppl. 2);S10 N Pakker, E Kroon, D Hall, M Roos, JSG Montaner, D Cooper, S Vella, J Lange, M Koot, P Reiss for the BI 1046 INCAS Study Team In conclusion, combination therapy with NVP+DDI+ZDV in treatment naïve patients demonstrates that sustained suppression of viral replication with reverse transcriptase inhibitors can result in both qualitative and quantitative immune restoration. Nevirapine provides new opportunities for combination treatment and the observed long term beneficial effect of triple therapy on the immune system is expected to contribute to immune reconstitution in both numeric and functional aspects. |
| OP2.2 | CAESAR STUDY: SURROGATE MARKER CHANGES IN RELATION TO CLINICAL RESPONSE Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP2.2 AIDS 1996, Vol. 10 (Suppl. 2);S10 1W Rozenbaum, 2N Clumeck, 3M de Brabander, 3M Moeremans, 4L Goh on behalf of the CAESAR Coordinating Committee Median CD4 cell rises and viral load reduction were significantly greater in the 3TC containing arms (p<0.001, pairwise t-test). This subgroup analysis is consistent with other published data on 3TC. |
| OP2-3 | THE EFFECT ON CEREBROSPINAL FLUID HIV RNA LEVELS AFTER INITIATION OF ZIDOVUDINE OR DIDANOSINE Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP2-3 AIDS 1996, Vol. 10 (Suppl. 2);S10 M. Gisslén, G. Norkrans, B. Svennerholm, L. Hagberg We conclude that zidovudine is a potent reducer of CNS viral load which is important for long teen neuroprotection. |
| OP2-4 | INCREASING FREQUENCY OF ANTIVIRAL NAÏVE PATIENTS HARBORING 215-MUTANT HIV-1 VIRUS DURING 1989-1996 Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP2.4 AIDS 1996, Vol. 10 (Suppl. 2);S11 A. Rubio, M. Leal, JA. Pineda C. Rey, M. Olivera, A. Sanchez-Quijano, J. Macias, E. Lissen In summary, we have found that since 1989 there is an augment of naïve patients harboring the 215-mutant virus in our cohort that seems to be dependent of their immunological state. Further experiments would be necessary analyzing clinical implications of these finding in order to improve the future management of new infected patients. |
| OP2.5 | AN OVERVIEW OF DRUG RESISTANCE DURING SAQUINAVIR TREATMENT Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP2.5 AIDS 1996, Vol. 10 (Suppl. 2);S11 E Race, SM Gilbert, JG Sheldon, AR Moffat, PW Tomlinson and JB Duncan The incidence of reduced sensitivity to SQV in the clinic is likely to be yet more significantly reduced by the use of other combinations which will substantially reduce viral replication and maintain viral load below the level of detection (eg SQV+ZDV+3TC or SQV+ritonavir). |
| OP3.1 | A RANDOMISED STUDY OF TWO COTRIMOXAZOLE (CTX) DOSES IN PRIMARY PROPHYLAXIS AGAINST PCP AND CEREBRAL TOXOPLASMOSIS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP3.1 AIDS 1996, Vol. 10 (Suppl. 2);S11 M.C. Payen, S. De Wit, J.P. Van Vooren, C.M. Farber, J.C. Legrand, J. Demonty, B. Sommereijns, N. Van Cutsem, N. Clumeck and the COPRIM Trial Group, Belgium In the intent to treat analysis, efficacy and tolerability of the 2 regimens are not statistically different. However, in the on-treatment analysis, the efficacy of the high dose appears to be better. Some larger studies are ongoing to confirm these results. In view of these preliminary results one could recommend to use the high dose (1 DS tablet daily) which can be reduced in case of intolerance. An escalating dose regimen could be another alternative. |
| OP3.2 | DOES THE MEASUREMENT OF CYTOMEGALOVIRUS (CMV) DNA CONCENTRATIONS USING THE DIGENE HYBRID CAPTURE ASSAY PREDICT RESPONSE TO THERAPY? Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP3.2 AIDS 1996, Vol. 10 (Suppl. 2);S11 C. Aitken. C, W. Barrett-Muir, S. Hill, D. Jeffries, J. Breuer, J. Parkin The hybrid capture assay offered an easy method of measuring CMV DNA levels directly on clinical samples. It was sensitive enough to show variations in load following therapy and therefore may be useful in predicting those patients who are likely to respond or relapse. |
| OP3.3 | EFFICACY OF DIFFERENT ANTIVIRAL TREATMENTS IN CYTOMEGALOVIRUS (CMV) NEUROLOGICAL COMPLICATIONS: EVALUATION BY QUANTITATIVE POLYMERASE CHAIN REACTION (PCR) ON CEREBROSPINAL FLUID (CSF). Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP3.3 AIDS 1996, Vol. 10 (Suppl. 2);S12 P. Cinque1, E. Pisa2, S. Racca1, S. Bossolasco1, R. Marenzi1, A. Lazzarin1, A. Linde3 In most of patients full dose GCV or/and PFA for 3 weeks is effective in reducing CMV replication in the nervous system. The clinical neurological response, however, is poor in most of the patients with CMV-E. |
| OP3.4 | CONTROLLED RANDOMIZED TRIAL OF GANCICLOVIR (GCV) IN COMPARISON TO HALF DOSE COMBINATION THERAPY WITH GCV AND FOSCARNET (PFA) IN CMV RETINITIS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP3.4 AIDS 1996, Vol. 10 (Suppl. 2);S12 A. Stoehr*, B. Salzberger#, V. Knospe+, A. Plettenberg*, K. U. Bartz-Schmitz#, H. Albrecht+, H. J. Stellbrink+, S. Thomalla#, M. Schrappe This randomized controlled trial is the first study showing the efficacy of half dose combination therapy of GCV and PFA versus standard therapy with GCV in treatment of CMV retinitis in HIV infected patients. Renal toxicity was not observed with this combination. |
| OP3.5 | TREATMENT OF CHRONIC HEPATITIS C WITH INTERFERON α IN PATIENTS INFECTED WITH THE HUMAN IMMUNODEFICIENCY VIRUS 1 Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP3.5 AIDS 1996, Vol. 10 (Suppl. 2);S12 S. Mauss, H. Jablonowski, H. Klinker*, A. Ulmer**, C. Niederau, D. Häussinger In contrast to hepatitis B cellular immunosuppression due to HIV does not influence the inflammatory activity of chronic hepatitis C. This supports the hypothesis of a direct cytopathic mechanism of HCV. The results indicate that IFN treatment of chronic hepatitis C in HIV+ patients is successful in a considerable number of individuals. Updated data on follow-up after treatment will be presented at the conference. |
| OP4.1 | THE SAFETY AND ANTIVIRAL EFFECT OF 1592U89, ALONE AND IN COMBINATION WITH ZIDOVUDINE IN HIV-1 INFECTED PATIENTS WITH CD4+ COUNTS 200-500 CELLS/mm3 Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP4.1 AIDS 1996, Vol. 10 (Suppl. 2);S12 A. Sonnerborg1, D. Lancaster2, R. Torres3, M. Thompson4, M. Saag5, R. Schooley6, J. Mulder7, B. Gazzard8, R. D'Aquilla9, M. Gurgui10, J. Feinberg11, M. Santin12, W. Lang13, P.R. Harrigan14, H. Steel14, S. Tortell14, C. Romero14 The extent of viral suppression and immunologic response observed with 1592U89 alone and in combination with ZDV, categorises 1592U89 as a highly potent nucleoside analogue, which together with the safety profile, merits further investigation. |
| OP4.2 | ANTIRETROVIRAL TREATMENT AND SHEDDING OF HIV IN SEMEN Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP4.2 AIDS 1996, Vol. 10 (Suppl. 2);S13 P.L. Vemazza, B.L. Gilliam, M. Flepp, J.R. Dyer, R. Cone, A.C. Frank, S.A. Fiscus, M.A. Cohen, J.J. Eron Reduction of HIV-RNA in blood is associated with a drop of HIV-RNA in semen. However, the effect of treatment on semen is less pronounced than in blood and is subject to a much higher variability. With the development of more potent drugs, the treatment effect on HIV in genital secretions may be an important target for future studies. |
| OP5.1 | EVIDENCE OF ACTIVITY OF VINORELBINE IN PATIENTS (PTS) WITH PREVIOUSLY TREATED AIDS-ASSOCIATED KAPOSI'S SARCOMA Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP5.1 AIDS 1996, Vol. 10 (Suppl. 2);S13 G. Nasti, D. Errante, M. Fasan, G. Rizzardini, G. Landonio, L. Pagani, C. Zeroli and U. Tirelli for the Italian Cooperative Group on AIDS and Tumors In conclusion, our results suggest that vinorelbine is active and well tolerated also in previously treated pts with AIDS-associated KS. Vinorelbine can be considered also for studies as first-line single agent or as a potential component of combination chemotherapy regimens for KS pts. |
| OP5.2 | INTRAPARTUM ZIDOVUDINE(ZDV) INFUSION ALONE FAILED TO REDUCE MATERNAL HIV-1 VIREMIA AND VERTICAL TRANSMISSION IN HIV-1 INFECTED PREGNANT WOMEN WITH NO PRIOR ANTENATAL CARE Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP5.2 AIDS 1996, Vol. 10 (Suppl. 2);S13 Virutamasen P1, Limpongsanurak S1, Ruxrungtham Kiat1, Thisayakom U1, Thaithamyanond P1, Reinprayoon D1, Hanvanich M1, Likitnukul S1, Sathapompongse K2, Chuansanti S3, Nimkam S4, Phanuphak P1 In our preliminary study, the intrapartum ZDV infusion alone failed to reduce both the maternal HIV-1 viremia and the risk of infection in infants. The recent HIV viral dynamic studies suggest that the t½ of HIV-1 virion is ~5.8 hrs, the too short duration of ZDV therapy (median < 5 hrs) could be a major explanation of the failure. Thus, in HIV-infected pregnant women with no prior ANC, a more potent antiretroviral agent or combination treatment in mothers and/or a post-exposure prophylaxis in infants may be essential and await further investigation. |
| OP6.1 | SAQUINAVIR PHARMACOKINETICS ALONE AND IN COMBINATION WITH RITONAVIR IN PATIENTS WITH HIV DISEASE Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP6.1 AIDS 1996, Vol. 10 (Suppl. 2);S13 C. Merry1,2, M. Barry1, F. Mulcahy2, J. Heavey2, J. Tjia1, S. Gibbons1, and D. Back1 For some patients SQV 600 mg t.d.s. results in very low plasma SQV levels and possibly little antiviral effect. Combination of SQV with RIT results in a significant drug interaction mediated by enzyme inhibition which exposes patients to very high SQV concentrations and potential toxicity. If combination therapy is considered then the dose of SQV should be greatly reduced. |
| OP6.2 | THERAPEUTIC VACCINATION: A RANDOMIZED CONTROLLED STUDY OF THE EFFECT OF rgp160 ON PROGRESSION OF IMMUNE DEFICIENCY AND VIRAL BURDEN Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP6.2 AIDS 1996, Vol. 10 (Suppl. 2);S14 Tsoukas, Chris M; Raboud, J; Bernard, N; Djurdjev, O; Cassol, S; Chernoff, D; Fong, I; Freedman, J; Gill, J; Goldberg, E; Lafreniere, R; Lee, S; Montaner, J; Poon, M-C; Rachlis, A; Schlech, W; Smith, G; Szabo, J; Todd, J; Thomas, R; Volvovítz, F In conclusion, although new or enhanced humoral and cellular immune responses were noted in rgp160 recipients in this controlled therapeutic vaccine study, no effect on viral burden was observed as determined by quantitative culture, antigenemia or plasma viremia. |
| OP6.3 | PLASMA VIREMIA IS MORE PREDICTIVE OF DISEASE PROGRESSION THAN CD4 COUNTS IN HIV INFECTED INDIVIDUALS WITH CD4 COUNTS > 500 IN A RANDOMIZED TRIAL OF IMMUNIZATION WITH rgp160 Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP6.3 AIDS 1996, Vol. 10 (Suppl. 2);S14 Raboud Janet, Tsoukas C, Bernard N, Djurdjev O, Cassol S, Chernoff D, Fong I, Freedman J, Gill J, Goldberg E, Lafreniere R, Lee S, Montaner J, Poon M-C, Rachlis A, Schlech W, Smith G, Szabo J, Todd, J, Thomas R, Volvovitz F In conclusion, in individuals with CD4 counts above 500 cells/mm3 who were randomized to receive VaxSyn immediately or after two years, baseline plasma HIV RNA was more predictive of progressive of disease than CD4 counts. Given the small number of AIDS defining events and the relative short follow-up of 36 months, the predictive value of plasma HIV RNA was surprisingly powerful in this cohort of healthy individuals with high CD4 counts. |
| OP6.4 | MULTICENTER STUDY OF SAFETY AND IMMUNOGENICITY OF HIV-1 rpg160 CANDIDATE VACCINE IN SEROPOSITIVE HIV-1 VOLUNTEERS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP6.4 AIDS 1996, Vol. 10 (Suppl. 2);S14 F.D. Goebel, J.W. Mannhalter, M.M. Eibl, RB. Belshe, P. Grob, V. Erfle, P.D.Griffiths, B. Wahren, K. Krohn, M. Kunschak , W. Engl for the European Multinational IMMUNO AIDS-vaccine study group In conclusion, the administration of rgp160 candidate vaccine appeared to be safe and immunogenic. T-cell-subsets, viral-load and clinical course did not seem to be affected by the vaccine in the whole study population. Subgroup analysis provided information important for further studies. |
| OP6.5 | THERAPEUTIC VACCINATION (p24-VLP) OF PATIENTS WITH ADVANCED HIV-1 INFECTION DOES NOT ALTER CD4 DECLINE Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP6.5 AIDS 1996, Vol. 10 (Suppl. 2);S14 DE Smith1, F Boag2, R Colebunders3, IVD Weller4, S Tchamouroff5, J Weber6, I Gow7, G Patou7 and DA Cooper1 In conclusion, while therapeutic vaccination with p24-VLP appears to be safe and well tolerated, no improvement in immunological markers could be detected in this large study of patients with advanced HIV infection. |
| OP6.6 | ANTIRETROVIRAL DRUG COST OFFSETS IN SEVEN DEVELOPED COUNTRIES: SAQUINAVIR, ZALCITABINE, AND ZIDOVUDINE Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP6.6 AIDS 1996, Vol. 10 (Suppl. 2);S15 Kit N. Simpson and Rebecca L. LaVallee We found that some of the cost of antiretroviral drugs in every country is offset by savings in other health care budget categories. However, the magnitude of the savings vary. Savings will be higher in regions where medical care production costs are high, but population severity mix may modify these relationships. These findings illustrate the inadvisability of judging the effects of AIDS treatments by comparing the results of different economic studies without controlling for differences in population mix and source of cost data. |
| OP7.1 | RANDOMIZED, DOUBLE-BLIND ONE YEAR STUDY OF THE IMMUNOLOGIC AND VIROLOGIC EFFECTS OF NEVIRAPINE, DIDANOSINE AND ZIDOVUDINE COMBINATIONS AMONG ANTIRETROVIRAL NAÏVE, AIDS-FREE PATIENTS WITH CD4 200-600 Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP7.1 AIDS 1996, Vol. 10 (Suppl. 2);S15 B Conway, JSG Montaner, D Cooper, S Vella, P Reiss, J Lange, M Harris, M Wainberg, S Kwok, J Sninsky, D Hall, M Myers and the INCAS STUDY GROUP Our data demonstrate NVP+ddI+ZDV has a substantially greater virological and immunological effect than ddI+ZDV or NVP+ZDV and that this effect persists for at least one year. Overall, NVP+ddl+ZDV is well tolerated. Our data lend support to the notion that suppression of viral replication can forestall, if not prevent, the development of drug resistance. |
| OP7.2 | PHENOTYPIC AND GENOTYPIC RESISTANCE EMERGENT IN NAÏVE HIV-1 PATIENTS TREATED WITH COMBINATIONS OF REVERSE TRANSCRIPTASE INHIBITORS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP7.2 AIDS 1996, Vol. 10 (Suppl. 2);S15 M.A. Wainberg and C Birch for the Boehringer-Ingelheim 1046 Study Team (INCAS Trial) Combination therapy with NVP+ZDV resulted in rapid, consistent emergence of resistance to NVP. By contrast, NVP+ddI+ZDV can produce profound sustained suppression of viral replication, delaying the emergence of NVP resistance. |
| OP7.3 | CORRELATION OF VIRAL LOAD IN PLASMA AND LYMPH NODE TISSUE IN PATIENTS UNDERGOING COMBINATION ANTIRETROVIRAL THERAPY Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP7.3 AIDS 1996, Vol. 10 (Suppl. 2);S15 M Harris, P Patenaude, P Cooperberg, D Filipenko, J Raboud, P Dailey, D Chernoff, J Todd, B Conway, JSG Montaner and The INCAS Study Group Our preliminary data suggest a substantial degree of suppression of viral replication in plasma and lymph nodes with combination antiretroviral therapy and with AZT+ddI+NVP, in particular. |
| OP7.4 | IMPACT OF TREATMENT CHANGES ON THE INTERPRETATION OF THE CONCORDE TRIAL Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP7.4 AIDS 1996, Vol. 10 (Suppl. 2);S16 AG Babiker, IR White, AS Walker, JH Darbyshire Open zidovudine before ARC or AIDS in the Def group is likely to have diluted any differences between Imm and Def. After correction for this dilution, both the estimated benefit of immediate treatment in delaying progression to ARC, AIDS or death and the estimated disadvantage of immediate treatment in accelerating death are somewhat increased, but both remain consistent with chance alone. |
| OP7.5 | REDUCTIONS IN HIV-1 DISEASE PROGRESSION FOR AZT/3TC RELATIVE TO CONTROL TREATMENTS: A META-ANALYSIS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP7.5 AIDS 1996, Vol. 10 (Suppl. 2);S16 Staszewski S1, Bartlett J2, Eron J3, Katlama C4, Johnson J5, Hill AM5 AZT/3TC combination treatment delays the progression of CDC B/C disease compared with control treatments. The results for progression to CDC C disease should be interpreted with caution given the small number of events. These findings are consistent with the observed surrogate marker benefit of AZT/3TC. |
| OP7.6 | PROLONGED IMMUNOLOGIC AND VIROLOGIC EFFECTS OF 3TC AND ZIDOVUDINE IN SUBJECTS WHO REMAINED ON BLINDED COMBINATION THERAPY BEYOND 52 WEEKS IN TWO NORTH AMERICAN CLINICAL TRIALS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP7.6 AIDS 1996, Vol. 10 (Suppl. 2);S16 Eron JJ1, Bartlett JA2, Johnson J3, Scott J3, Hill-Price S3, Keller A3, and Smiley ML3 In a selected subset of ZDV-naïve and ZDV-experienced subjects who received blinded 3TC/ZDV therapy beyond 52 weeks, immunologic and virologic benefits of this combination persisted up to 76 weeks. |
| SS5.6 | PHARMACOKINETICS OF RITONAVIR-SAQUINAVIR COMBINATION THERAPY Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. SS5.6 AIDS 1996, Vol. 10 (Suppl. 2);S16 Cameron DW1, Hsu A9, Granneman GR9, Sun E9, McMahon D2, Farthing C3, Poretz D4, Markowitz M5, Cohen C6, Follansbee S7, Mellors J2, Ho D5, Xu Y9, Rode R9, Salgo M8, Leonard P9 A pilot study of RTV-SQV combination therapy is currently underway in approximately 140 HIV-infected patients who have discontinued their RT inhibitor therapy. The following regimens are being studied; (A) RTV 400 mg bid + SQV 400 mg bid, (B) RTV 600 mg bid + SQV 400 mg bid, (C) RTV 400 mg tid + SQV 400 mg tid, and (D) RTV 600 mg bid + SQV 600 mg bid. Median RNA declines were 2.74 and 3.06 log after 12 weeks in regimens A and B, respectively, and 2.09 and 2.19 after 6 weeks in regimens C and D, respectively. Pharmacokinetic results performed in a subset of patients are available for regimens A and B. Mean (SD) RTV 12-hour AUCs were 46 (16) and 96 (32) µg•hr/ml, and mean SQV 12-hour AUCs were 16 (11) and 22 (9)µg•hr/ml, in regimens A and B, respectively. |
| OP8.1 | SAQUINAVIR + ZALCITABINE VS SAQUINAVIR OR ZALCITABINE MONOTHERAPY IN HIV-INFECTED PATIENTS DISCONTINUING OR INTOLERANT TO ZIDOVUDINE : RESULTS OF A RANDOMIZED, DOUBLE BLIND TRIAL Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP8.1 AIDS 1996, Vol. 10 (Suppl. 2);S17 Haubrich R1, Burger H U2, Beattie D2, Donatacci L2, Salgo, M P2, and the NV14256 Study Team Combination therapy with SQV+ddC prolongs survival and delays the onset of AIDS defining events or death compared to ddC monotherapy. |
| OP8.2 | THE EFFECTS OF AN ANTIRETROVIRAL TRIPLE COMBINATION WITH RITONAVIR, AZT AND 3TC Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP8.2 AIDS 1996, Vol. 10 (Suppl. 2);S17 D.W. Notermans, F. de Wolf1, N.A. Foudraine2, P.L. Meenhorst3, R.H. Kauffman4, H. McDade, C. Goodwin5, J. Leonard, R. Mills6, J.J. de Jong, H.M. van Egmond1, F. Miedema7, W. Cavert, A.T. Haase8 and S.A. Danner1 The results show that ritonavir combined with AZT and 3TC has a potent effect and is capable of suppressing HIV below the cut-off of the Roche Amplicor RNA PCR (median 319 copies/ml) in a large number of patients. In addition data on development of genotypic resistance will be presented. |
| OP8.3 | COMPARISON OF RITONAVIR AND INDINAVIR IN HIV PATIENTS WITH ADVANCED DISEASE: A BELGIAN OUTCOME TRIAL Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 18.3 AIDS 1996, Vol. 10 (Suppl. 2);S17 N. Clumeck, B. Colebunders, S. De Wit, K. Kabeya and the Picasso Trial Group This programme illustrates the concept of outcome trials which evaluate the global efficiency of therapeutical interventions taking into account clinical events, survival, quality of life, compliance, cost, psychological and social consequences. This differs from the classical efficacy trials. With the increasing number of available HIV compounds and other therapeutical interventions, efficacy trials will become more and more difficult to set up. In this context, outcome trials may provide key information in terms of therapeutical strategies in the setting of real life clinical care. Data on the six first months of follow-up will be presented. |
| OP9.1 | A PILOT STUDY OF SAFETY AND ANTIVIRAL ACTIVITY OF THE COMBINATION
OF STAVUDINE, DIDANOSINE AND NELFINAVIR IN HIV-INFECTED SUBJECTS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP9.1 AIDS 1996, Vol. 10 (Suppl. 2);S17 L. Pedneault1, R Elion2, M. Adler1, R Anderson3, S. Mohanty1, C. Knupp4, S. Kaul4, B. Kerr3, A. Cross1, L. Dunkle1 In conclusion, these preliminary findings suggest that d4T + ddI + nelfmavir combination therapy may have potent antiviral effect and is well tolerated. Results of extended follow-up will be presented. |
| OP9.2 | HIV-1 VARIANTS ISOLATED FROM PATIENTS TREATED WITH THE PROTEASE INHIBITOR, NELFINAVIR ARE NOT CROSS-RESISTANT TO OTHER PROTEASE INHIBITORS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP9.2 AIDS 1996, Vol. 10 (Suppl. 2);S18 A.K. Patick1, M. Durant2, Y. Cao2, T. Ho2, P. Zhou2, M.R. Keller1, J. Peterkin1, S. Chapman1, R. Anderson1, D. Ho2 and M. Markowitz2 This data suggests that the pathway to resistance to nelfinavir is unique and mediated through D30N. Furthermore, the full susceptibility of nelfinavir-resistant isolates to other protease inhibitors suggests that subsequent treatment with other protease inhibitors may be effective. |
|
POSTERS Abstracts P1 thru P131, Page S19 TO S53 |
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| Antiviral Resistance Abstracts P1 to P17, pages S19 to S23 |
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| P1 | ZIDOVUDINE-RESISTANT VARIANTS OF HIV-1 IN LUNG. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P1 AIDS 1996, Vol. 10 (Suppl. 2);S19 A J Gates, R J Coker, R Miller, D M Mitchell, J D Williamson, J R Clarke. The genotypic patterns of ZDV resistance were distinguishable between the blood and lung proviral HIV-1 populations in all the patients tested (to date, 12 patients). The extent of variation was greater in the phagocytic cells from each body compartment. We conclude that the data obtained in this study indicate a separate evolution of HIV-1 in the lung. |
| P2 | DRUG RESISTANCE PATTERNS IN HIV-1 ISOLATES FROM PATIENTS RECEIVING PROLONGED AZT/3TC COMBINATION THERAPY Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P2 AIDS 1996, Vol. 10 (Suppl. 2);S19 Stuart Bloor for the FASP Resistance Study Group* Sequence analysis of the HIV-1 RT of the recombinant virus was performed to determine whether a consistent mutation pattern could be detected in isolates showing resistance to both AZT and 3TC. The AZT sensitivity of recombinant clones containing varying fragments of the target RT from clinical samples were compared in order to map dual-resistance mutations. Such resistance appears to map to both the 5' and 3' ends of RT and is accompanied by a significant number of the known AZT resistance mutations. It is anticipated that site-directed mutagenesis experiments will further elucidate the molecular basis of this dual resistance. |
| P3 | MUTATIONS WITHIN THE HIV 1 PROTEASE AND REVERSE TRANSCRIPTASE GENE IN HIV 1 INFECTED PATIENTS UNDER TREATMENT WITH AZT AND SAQUINAVIR Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P3 AIDS 1996, Vol. 10 (Suppl. 2);S19 Storch-Hagenlocher B, Haas J, Ehrhart K, Freitag, M Wagner H, Hacke W, Wildemann B Our study suggests that in vivo the development of drug resistance conferring mutations within the PR coding region may be delayed by comedication with AZT. Combination therapy with Saquinavir does not prevent development of mutations related to reduced susceptibility to AZT. |
| P4 | DOES AZT+ddC TREATMENT INFLUENCE THE OUTCOME OF A SUBSEQUENT SHIFT TO AZT+3TC? Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P4 AIDS 1996, Vol. 10 (Suppl. 2);S19 C. Magni, A. Capetti, P. Bonfanti, G. Rizzardini Obviously ours is only an alerting observation on a small number of cases which requires further studies including viral load, viral genotypic characterization and study or cellular enzymes to assess whether in this and perhaps other cases mutations may contraindicate some therapy switches. If the present data are confirmed, they might be due to the appearance or KG5R mutation. that induces resistance to ddC and 3TC nod is not reversed by the 3TC-induced MI84Y mutation, or by a deficiency in cellular kinases' activity, shown by Magnani et al. |
| P5 | IN VITRO SELECTION OF HIGH LEVEL QUINOXALINE (HBY097) RESISTANCE USING A PATIENT ISOLATE DISPLAYING MULTIDRUG RESISTANT PHENOTYPE Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P5 AIDS 1996, Vol. 10 (Suppl. 2);S20 A-M Vandamme1, J-C Schmit1, J Balzarini1, M Witvrouw1, Kristel Van Laethem1, J-P Kleim2, J Desmyter1, E De Clercq1 Since the emergence of HBY097 resistance was not delayed when the 184V mutation was maintained, these results argue against a sequential therapy with HBY097 or 3TC as suggested from the observation that the RT harboring V184 has an increased fidelity (Wainberg et al, Science 271, 1282, 1996), Rather potent drugs such as HBY097 should be used in combination therapies. |
| P6 | RESISTANCE EMERGENCE TO ZIDOVUDINE (ZDV) AND LAMIVUDINE (3TC™)IN HIV-1-INFECTED PATIENTS IN AN ONGOING OPEN LABEL TRIAL Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P6 AIDS 1996, Vol. 10 (Suppl. 2);S20 S. Rusconi, M P de Pasquale, L Milazzo, G Moscatelli, S Kurtagic, A d'Arminio-Monforte and M Galli. To compare the resistance pattern of ZDV plus 3TC™in ZDV-experienced patients, we chose to study 3 patients enrolled in NUCB 3004, an open label trial of ZDV 250 mg bid plus 3TC™150 mg bid in patients with CD4 cell counts lower than 50/μL or who had a 50% decrease in their CD4 cells during the previous six months. |
| P7 | CD4 RESPONSE TO MONOTHERAPY WITH STAVUDINE IN ZIDOVUDINE (ZDV) EXPERIENCED PATIENTS: LACK OF CORRELATION OF V75T MUTATION WITH THERAPEUTICAL FAILURE. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P7 AIDS 1996, Vol. 10 (Suppl. 2);S20 S. De Wit, A. Papadopoulos, M. Debier, B. Sommereijns, N. Clumeck. No V75T mutation was found. There was a tendency for patients with higher CD4 cell count at baseline (above 240/mm³) or longer previous ZDV exposure (more than 3 years) to benefit longer from Stavudine monotherapy, although this was not statistically significant. No correlation was found between CD4 response and age, sex or race. Our data confirm that ZDV experienced patients may benefit from Stavudine for a significant period of time. We also confirm preliminary in vitro and in vivo data showing that occurrence of the V75T mutation is a rare event which is not correlated with the CD4 response. In this respect the role of routine evaluation of this mutation in the clinical setting is highly questionable. This trial being currently analyzed, correlation between the dose of Stavudine and CD4 response will be presented. |
| P8 | DIFFERENT MUTATIONAL PATHWAYS OF THE HIV-1 RT GENE ARE DEFINED BY ALTERNATIVE EXPERIMENTAL PROTOCOLS APPLIED TO GENERATE IN VITRO RESISTANCE OF HIV-1 TO HBY 097 Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P8 AIDS 1996, Vol. 10 (Suppl. 2);S20 Gunther Rieb, Irvin Winkler, Manfred Rösner, Reinhard Kirsch, Helga Rübsamen-Waigmann*, Arno Paessens*, and Jörg-Peter Kleim. We conclude that lowering the selective pressure of HEY 097 results in avoidance of the detrimental G190→ E RT by HIV-1 in vitro. Consistently, these findings underline the importance of pharmacokinetic parameters for the type of mutations which appear in HIV-1 infected patients undergoing therapy. |
| P9 | PHENOTYPIC RESISTANCE IN PLASMA OF NAÏVE HIV-1 PATIENTS TREATED WITH COMBINATIONS OF REVERSE TRANSCRIPTASE INHIBITORS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P9 AIDS 1996, Vol. 10 (Suppl. 2);S21 D Hall and C-K Shih Combination therapy with NVP+ZDV results in rapid, consistent emergence of resistance to NVP. By contrast, NVP+DDI +ZDV can produce profound sustained suppression of viral replication, and even for those patients from whom virus can be isolated, the emergent NVP resistance is less. There is a trend toward delayed development of ZDV resistance with NVP containing regimens when compared to ZDV+DDI. Further resistance testing after 12 months of treatment will test this hypothesis. |
| P10 | ANTIVIRAL EFFECTS OF ADEFOVIR (PMEA) AGAINST IN VITRO REPLICATION OF WILD TYPE AND DRUG RESISTANT HUMAN CYTOMEGALOVIRUS (HCMV) CLINICAL ISOLATES Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P10 AIDS 1996, Vol. 10 (Suppl. 2);S21 J.M.Cherrington, M.D.Fuller, and M.S. Chen. Additional in vitro experiments were carried out to investigate the antiviral effects of adefovir in combination with other anti-HCMV compounds: ganciclovir, foscarnet and cidofovir. All three of these combinations showed additive inhibition of HCMV replication and importantly, no antiviral antagonism was measured for any of the adefovir combinations. |
| P11 | RECOGNITION OF MUTATIONS ASSOCIATED WITH RESISTANCE TO HIV REVERSE TRANSCRIPTASE INHIBITORS USING A NEW LINE PROBE ASSAY. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P11 AIDS 1996, Vol. 10 (Suppl. 2);S21 Ma Gómez-Cano, N. Villalba, V. Soriano, L. Stuyver*, A. Mas, R. Bravo, J. González-Lahoz. The most commonly found were mutations at positions 215, 70 and 41, all of them associated with ZDY-resistance. In contrast, the 74 and 184 codon mutations were recognized in only one subject despite all these patients had been treated with DDI and/or DDC for long periods of time up to recent weeks before blood collection for the current analysis. Globally, results using LiPA and PCR were in agreement in samples with pure virus populations (wild or mutant). However, LiPA seemed to be more specific, allowing less specimens to be interpreted as carrying mixed populations. |
| P12 | HIV-1 FROM PATIENTS IN A PHASE II CLINICAL TRIAL WITH THE PROTEINASE INHIBITOR (PI) SAQUINAVIR (SQV) TAKEN IN COMBINATION WITH RT INIUBITORS (RTI's) EXHIBITS VERY LITTLE REDUCED SENSITIVITY TO OTHER PI'S. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P12 AIDS 1996, Vol. 10 (Suppl. 2);S21 P.W Tomlinson, J.C. Craig, A.R. Moffatt, N.A. Roberts, J.G. Sheldon, L. Whittaker and I.B. Duncan. In clinical trial ACTG 229 it has been estimated previously that 29% of patients' virus isolates show an L90M change by weeks 40-48. It would appear that in this study only 20% (1 out of 5) of post-treatment virus isolates containing this change at position 90 had reduced sensitivity to other PIs, in contrast with the assertion made by Condra et al from a study with IND that treatment with any PI will limit the benefit of subsequent treatment with others. The anticipated improvement in antiviral efficacy through using SQY in more effective drug combinations, eg SQY+ZDY+3TC or SQY+RIT, will likely further reduce the emergence of resistance to this drug and coresistance with other PI's. |
| P13 | SAQUINAVIR (SQV) DOES NOT SELECT FOR UNIVERSAL CO-RESISTANCE WITH OTHER PROTEINASE INHIBITORS (PI) IN PATIENTS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P13 AIDS 1996, Vol. 10 (Suppl. 2);S22 C Craig, E Race, J Sheldon, L Whitlaker, P W Tomlinson, A Moffat, S Gilbert, IB Duncan, NA Roberts The study is ongoing. Meanwhile, we estimate that 20% of virus isolates from patients after 25-78 weeks combination therapy with SQV + AZ:J:± ddC show phenotypic resistance to SQV (trial NV-14255). To date, only half of these isolates (10% of total) are predicted to show any reduced sensitivity to those other PI studied. These data indicate that SQV is not akin to indinavir in supporting universally reduced sensitivity to other PI. A further reduction in this potential is predicted through the improved application of SQV in combination regimens (e.g. SQV+ZDV+3TC,SQV + ritonavir), which will substantially reduce viral replication and viral load to below the level of detection. Therefore SQV, currently the best tolerated PI, can be considered as a drug of choice for any combination treatment. |
| P14 | IN VITRO SELECTION OF HIV-1 VARIANTS WITH REDUCED SENSITIVITY TO SAQUINAVIR AND RITONAVIR BY SUCCESSIVE SEQUENTIAL PASSAGE. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P14 AIDS 1996, Vol. 10 (Suppl. 2);S22 S M Gilbert, R. Jupp, A.R. Moffatt, J.G. Sheldon, E. Race Decreased sensitivity to ritonavir in vitro occurs no more quickly, and to a lesser degree, in virus carrying saquinavir resistance mutations when compared with wild type. |
| P15 | LOW OCCURRENCE OF REDUCED SENSITIVITY TO SAQUINAVIR IN ANTIVIRAL COMBINATION: RESULTS FROM A PHASE III CLINICAL TRIAL (NV14256). Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P15 AIDS 1996, Vol. 10 (Suppl. 2);S22 E. Race, S.M. Gilbert, J.G. Sheldon, A.R. Moffat, P.W. Tomlinson, and I.B. Duncan. The incidence of reduced sensitivity to SQV in the clinic is likely to be yet more significantly reduced by the use of other combinations which will substantially reduce viral replication, and maintain viral load below the level of detection (eg SQV+ ZDV+3TC or SQV+ritonavir). |
| P16 | CHANGES IN VIROLOGICAL MARKERS DURING PROLONGED SAQUINAVIR MONOTHERAPY Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P16 AIDS 1996, Vol. 10 (Suppl. 2);S22 S. Kaye1, A.S.Pym2, S. Galpin2, R.S.Tedder1, J.N.Weber2 and I.B.Duncan3. Three patients progressed to AIDS many months after the emergence of L90M. The median change in CD4 count was 80 cells/mm³ (16% below baseline), and the median change in viral load +0.20 log (range - 0.15 log to + 1.49 log) Overall, the slow changes in surrogate markers and rate of progression in this patient population indicated a maintained disease stability, and the key mutations which have been associated with reduced sensitivity to SQV appeared not to have immediate effects on progression. The incidence of reduced sensitivity to SQV in the clinic is likely to be more significantly reduced. along with an increase in efficacy, by the use of drug combinations which will substantially reduce viral replication, and maintain viral load below the level of detection (e.g. SQV+ZDV+3TC or SQV+ritonavir). |
| P17 | AN ASSESSMENT OF PHENOTYPIC AND GENOTYPIC CO-RESISTANCE TO INHIBITORS OF HIV PROTEINASE FOLLOWING THERAPY WITH HIGH DOSE SAQUINAVIR Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P17 AIDS 1996, Vol. 10 (Suppl. 2);S23 L Whittaker1, J M Schapiro2, J C Craig1, M A Winters2, P W Tomlinson1, J G Sheldon1, A R Moffatt1, H Jacobsen3, IB Duncan1, S Gilbert1, S Crawford2, TC Merigan2. These data suggest that exposure to higher drug levels of saquinavir for 24 weeks even as monotherapy, results in a low incidence of selection for multidrug resistance, and in the majority of cases does not compromise options for future therapy with other proteinase inhibitors. |
| Clinical Pharmacology Abstracts P18 to P28, pages S23 to S25 |
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| P18 | APPLICATION OF INTERRUPTED COURSE OF AZT THERAPY OF THE PATIENTS WITH EARLY HIV INFECTION Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P18 AIDS 1996, Vol. 10 (Suppl. 2);S23 O.G. Yurin, A.V. Kravchenko, B.M. Gruzdev*, L.A. Avdeeva, E.S.Gorbachova*, V.V.Pokrovsky The clinical effectivety of interrupted and continuous courses of AZT therapy in patients with early HIV-infection during 1 year of treatment is practically the same. However, the interrupted course is twice cheaper and more acceptable for patients emotionally. They break off the interrupted course of treatment rare. The comparison of the effectivety of these courses during more long time and the study of the influence of the interrupted course for the development of the resistance to AZT therapy should be provided. |
| P19 | THE SAFETY AND PHARMACOKINETICS OF GW1592U89, ZIDOVUDINE (ZDV) AND LAMIVUDINE (3TC) ALONE AND IN COMBINATION AFTER SINGLE-DOSE ADMINISTRATION IN HIV-INFECTED PATIENTS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P19 AIDS 1996, Vol. 10 (Suppl. 2);S23 Symonds WT1, McDowell J1, Chittick G1, Moss J2, Bye A2 All study treatments were well tolerated. No significant pharmacokinetic interactions were detected. Administration of GW1592U89 in double or triple combinations with AZT and/or 3TC will not require any dosage adjustments. |
| P20 | PHASE I TRIAL WITH FOZIVUDINE TIDOXIL (BM 21.1290): A CANDIDATE COMPOUND FOR FUTURE COMBINATION THERAPIES Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P20 AIDS 1996, Vol. 10 (Suppl. 2);S23 Bogner Johannes R*, Röcken M*, Boerner D+, Jost, V§, Thoma-Greber E*, Herrmann DBJ+, Hoegl L*, Plewig G*, Goebel F-D* The ZDV-conjugate FZT is safe and well tolerated in the nine tested doses. Phase II trials are warranted. Additional data on virological efficacy will be available by October 1996 from an ongoing Phase I/II trial. The new compound will possibly contribute to a better tolerance of future combination regimens, especially in patients with ZDV intolerance. |
| P21 | α1-ACID GLYCOPROTEIN CONCENTRATIONS IN HIV DISEASE - IMPLICATIONS FOR TREATMENT WITH PROTEASE INHIBITORS. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P21 AIDS 1996, Vol. 10 (Suppl. 2);S24 C. Merry1,2, F. Mulcahy2, S. Gibbons1, J. Lloyd1, M. Barry1 & D. Back1 AAG concentrations are elevated in patients with HIV disease when compared with healthy volunteers. This elevation is not influenced by the degree of immunosuppression. Therefore the influence of elevated AAG concentration on plasma protein binding and anti-HIV effect of the new protease inhibitors will be evident at all stages of HIV disease. |
| P22 | TOLERABILITY OF RITONAVIR AND SAQLIINAVIR DURING TRIPLE THERAPY FOR HIV INFECTION Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P22 AIDS 1996, Vol. 10 (Suppl. 2);S24 C. Merry1,2, M. Ryan2, F. Mulcahy2, J. Heavey2, S. Gibbons1, M. Barry1 & D. Back1. Thus combination therapy with ZDV + 3TC + SQV was bener tolerated than ZDV + 3TC + RIT where adverse effects resulted in discontinuation of therapy in 30% of patients. |
| P23 | PENETRATION OF 3'-AMINO-3'-DEOXYTHYMIDINE, A CYTOTOXIC METABOLITE OF ZIDOVUDINE, INTO THE CEREBROSPINAL FLUID OF HIV-1-INFECTED PATIENTS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P23 AIDS 1996, Vol. 10 (Suppl. 2);S24 R.M.W. Hoetelmans1, C.L.Kraaijeveld2, P.L. Meenhorst3, JW. Mulder3, D.M. Burger4, C.H.W.Koks1, J.H. Beijnen1. AMT, a cytotoxic metabolite of ZDV, is detected in the CSF of HIV-1-infected patients. The median AMT CSF to plasma concentration ratio is equal to unity. The observed higher AMT CSF concentrations in patients with cerebral toxoplasmosis might be caused by the presence of active toxoplasmosis in the brain, or might indicate that the formation of AMT is increased and/or the elimination of this cytotoxic metabolite is decreased. This would be the first reported in vivo drug interaction regarding AMT. The clinical relevance of AMT as a potentially cytotoxic metabolite of ZDV, however, remains to be established. |
| P24 | DIGESTIVE ABSORPTION OF SAQUINAVIR IN AIDS PATIENTS WITH SEVERE DIARRHEA OR WASTING SYNDROME. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P24 AIDS 1996, Vol. 10 (Suppl. 2);S25 *Kodjo. A, **Dumitrescu. L, *Crivat. M, ***Trout. H, ****Dohin. E. **Vittecoq. D, ****Goehrs, JM. *Bergamo, JF - **Service de Médecine Interne-Höpital Paul brousse These preliminary data show that plasma concentrations of SQV administered to HIV pts with severe diarrhea or wasting syndrome are at least equal to levels achieved in healthy volunteers. |
| P25 | DRUG COSTS FOR HIV/AIDS TREATMENT IN BRITISH COLUMBIA. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P25 AIDS 1996, Vol. 10 (Suppl. 2);S25 AH Anis, Hogg, RS, Montener, JSG, Yip, B, Wang, W, O'Shaughnessy, MV, Schechter, MT Our data demonstrate that the average annual drug costs for persons with HIV/ AIDS in BC have remained relatively low and stable over the study period. Important cost drivers were participant's socioeconomic status (by coverage level) and rate of disease progression as measured by CD4 counts, hospitalization events and duration of illness. |
| P26 | SAQUINAVIR DRUG INTERACTIONS AGAINST HUMAN CYTOCHROME P-450 3A4. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P26 AIDS 1996, Vol. 10 (Suppl. 2);S25 Foster, B.C.1, Wilson, D.L.1, Gallicano, K.1, Sahai, J.2 and Bouchard, J.3 This study has validated the checkerbox titration method as a rapid, inexpensive means of examining multiple drug interactions. |
| P27 | IN VITRO ACTIVATION OF NUCLEOSIDE ANALOGUE DRUGS USED IN COMBINATION IN THE MRC QUATTRO TRIAL Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P27 AIDS 1996, Vol. 10 (Suppl. 2);S25 D. Back, G. Veal, S. Khoo & M. Barry. Nucleoside analogue drugs require intracellular metabolism to their active triphosphate forms. It is important that these agents do not compete with each other for intracellular kinase. This study investigates the activation pathways of zidovudine (ZDV), zalcitabine (ddC) and lamivudine (3TC) in MOLT-4 cells, when incubated in combination at clinically achieved concentrations. These three drugs are currently being assessed in combination in the MRC Quattro trial. |
| P28 | ZIDOVUDINE PHOSPHORYLATION IN HIV-INFECTED THAI PATIENTS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P28 AIDS 1996, Vol. 10 (Suppl. 2);S25 D. Phiboonbanakit1, S. Khoo1, Y. Watanagoon2, K. NaBangchang2, P. Hoggard1, S. Gibbons1, M. Barry1 & D. Back1. Zidovudine (ZDV) requires intracellular phosphorylation to ZDV-triphosphate prior to the inhibition of HIV replication. It is clear that the ability to measure ZDV intracellular phosphorylated metabolites in patients with HJV is of seminal importance in our understanding of the clinical pharmacology of ZDV. |
| Combination Trials Abstracts P29 to P55, pages S26 to S32 |
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| P29 | EFFECT OF COMBINATION ZIDOVUDINE (ZDV) AND DIDANOSINE (DDI) THERAPY ON 40 HIV-1 INFECTED CHILDREN. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P29 AIDS 1996, Vol. 10 (Suppl. 2);S26 C. Courpotin, C. Dolfus, F. Parnet-Mathieu, J.C. Nicolas and G. Lasfargues. These results show the efficiency of ZDV + DDI to decrease the viral load and probably the virus replication on previously treated children. No clinical adverse effects were noted. The study was too short to evaluate the clinical impact of bi-therapy and further investigations will be needed. |
| P30 | EFFECTIVNESS ON SURVIVAL OF ANTIRETROVIRAL THERAPY IN THE COMMUNITY. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P30 AIDS 1996, Vol. 10 (Suppl. 2);S26 H Knobel, C Serrano, M Pavesi, P Hernández, P Saballs, JL Gimeno, JL López Colomés. a) Any therapy was better than no therapy. b) Switching to DDI or adding DDC or DDI was better than continuing AZT monotherapy. c) Combination therapy is tolerated as well as monotherapy. These findings are observational, however they are consistent with findings from recent clinical trials. |
| P31 | LONG TIME RETROSPECTIVE STUDY OF COMPARATION OF MONOTHERAPY WITH AZT IN COMPARATION WITH COMBINATION OF AZT + DOC, AZT + DDI AND AZT +3TC. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P31 AIDS 1996, Vol. 10 (Suppl. 2);S26 Mireles-Vieyra, M.P., Feregrino-Goyos M., Torra-Giner V., Higuera-Ramirez F., Alvarado-Diez, R., Gomez-Caro,W.H. All the patients who begin his HIV treatment with combined antivirals had a better quality of life, less new AIDS complications, less prob of death, better evol in CD4 counts and minor viral load specially in 3TC+AZTin the first year. After one y. with same therapy the benefits were less important. |
| P32 | D4T (STAVUDINE): ALONE OR COMBINED?? Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P32 AIDS 1996, Vol. 10 (Suppl. 2);S26 Manuel Feregrino-Goyos, Gomez-Caro, W.H., Alvarado-Diez, R., Mireles-Vieyra M.P., Higuera-Ramirez F., Torras-Giner V. The combination of D4T with 3TC or D4T + DDI has a very high antiviral power in advanced HIV/AIDS patients and has haematological, immunological, and clinical more important benefits than monotherapy of D4T. That combination are synergistic and maybe they are a good and less expansive treatment in advanced HIV disease than protease inhibitors. The triple combo of DDI+ 3TC + D4T was start evaluation. |
| P33 | D4T (STAVUDINE): ALONE OR COMBINED?? Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P33 AIDS 1996, Vol. 10 (Suppl. 2);S27 Gomez-Caro, W. Humberto, Feregrino-Goyos, M., Alvarado-Diez R., Mireles Vieyra, M.P., Torras-Giner, V. In December 1995 FDA approved Saquinavir for combination with other 2 antivirals drugs for the treatment of HIV/AIDS. He describe now our experience with 7 patients who begin therapy with Saquinavir in the last 7 months in México. |
| P34 | EARLY MEXICAN EXPERIENCE WITH RITONAVIR TREATMENT IN TRIPLE COMBO. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P34 AIDS 1996, Vol. 10 (Suppl. 2);S27 Manuel Feregrino-Goyos, W.H. Gomez-Caro, R. Alvarado-Diez, M.P. Mireles-Vieyra We wish evaluate the evolution and effectiveness of the treatment with RITONAVIR combined with 2 Nucleosides analogs inhibitors of Reverse Transcriptase in HIV patient with very long time of previous treatment and failure in their response to previous therapies. |
| P35 | POSTER WITHDRAWN Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P35 AIDS 1996, Vol. 10 (Suppl. 2);S27 |
| P36 | ISS 047 TRIAL: AZT+ddI VERSUS AZT+ddI+NEVIRAPINE IN ANTIRETROVIRAL-NAÏVE PATIENTS WITH AIDS OR CD4+ <200/mm³. PRELIMINARY RESULTS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P36 AIDS 1996, Vol. 10 (Suppl. 2);S27 Floridia M, Tomino C, Fragola V, Bucciardini R, Ricciardulli D, Weimer LE, Galluzzo MC, Giannini G, Pirillo MF, Andreotti M, Vella S. Although further follow up is needed and data are still blinded, these preliminary results suggest an acceptable tolerability and a good effect on CD4 of both AZT+ddl and AZT+ddl+nevirapine in this population of antiretroviral-naïve patients with advanced HIV infection. An extensive virological evaluation (HIV-1 RNA, viral phenotype, resistance), is currently being performed on those patients who reached 24 weeks of treatment. |
| P37 | THE INCIDENCE OF OPPORTUNISTIC INFECTIONS AND HOSPITALISATIONS IN HIV PATIENTS TREATED WITH LAMIVUDINE/ZIDOVUDINE Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P37 AIDS 1996, Vol. 10 (Suppl. 2);S28 L Lacey, A Hill, J Mauskopf During the periods of observation, patients on combination therapy with LAM/ZDV experienced fewer opportunistic illnesses than a comparable group of patients treated with ZDV alone. Fewer hospital stays for both CDC-C events and other causes were also observed in the combination therapy group. |
| P38 | HIGH COMPLIANCE WITH ZALCITABINE, USED IN COMBINATION WITH ZIDOVUDINE. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P38 AIDS 1996, Vol. 10 (Suppl. 2);S28 Sette P., Zaccarelli M., Alba L., Ferri F. *, Balestra P. *, Rosci M. A. Our experience suggests that Zalcitabine, due to the high compliance, in addition to the safety and efficacy, observed among our sample of patients, may be considered a first choice drug to 1l&.ein combination therapy with other nucleoside analogous and/or protease inhibitors. |
| P39 | EPIVIR ™ (3TC) NORTH AMERICAN EXPANDED ACCESS PROGRAM - SAFETY EXPERIENCE BY GENDER AND ETHNIC ORIGIN Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P39 AIDS 1996, Vol. 10 (Suppl. 2);S28 M Conant*, P Self**, E Liao**, P Jarrett**, K Sturgen**, D Cocchetto**, M Rubin**. The proportion of female and minority HIV cases reported in the US has increased appreciably in recent years. We present the results of an analysis of the safety data from the Epivir North American Expanded Access Program by gender and ethnic origin. |
| P40 | IMPACT OF LAMIVUDINE+ZIDOVUDINE COMBINATION THERAPY ON HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN PEOPLE WITH HIV INFECTION Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P40 AIDS 1996, Vol. 10 (Suppl. 2);S28 J Scotto-Lennox, M Burt. Despite limited power to detect statistical significance, the cumulative evidence from these two trials indicates that LAM/ZDV combination therapy preserved or improved HRQOL in both antiretroviral therapy-naïve and therapy-experienced people with HIV infection |
| P41 | ADDING SAQUINAVIR TO D4T IN ADVANCED HIV INFECTED PATIENTS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P41 AIDS 1996, Vol. 10 (Suppl. 2);S29 OT Rutschmann, L Kaiser, M Fathi, L Perrin, B Hirschel. Adding Saquinavir to d4T was followed by decreases in HIV-1 RNA greater than expected. This could be explained by an increase in Saquinavir plasma levels. |
| P42 | TREATMENT WITH ZIDOVUDINE AND LAMIVUDINE COMBINATION IN HIV(+) PATIENTS: A PRELIMINARY REPORT Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P42 AIDS 1996, Vol. 10 (Suppl. 2);S29 P.Greka1, S.Michaliou1, D.Kavatha2, A.Tsitsika2, P.Gargalianos3, J.Kosmidis3, G.Saroglou1, M.Lazanas1 During follow-up 4 (14.8%) pts devetoped an AIDS-defining condition: 2 (7.4%) CMV retinitis 4 and 6 mo post therapy initiation, 1 (2.7%) CMV enteritis at 6 mo and 1 (3.7%) cryptosporidiosis at 4 mo. It is concluded that mv and 3TC provokes an increase in CD4 (+) cell count accompanied by a decrease in viral load in HIV (+) individuals with a CD (+) cell count ≤ 300μl, mainly manifested at 4, 5 and 6 months post therapy initiation. |
| P43 | AGGRESSIVE USE OF COMBINATION ANTIRETROVIRALS BY AUSTRALIAN GENERAL PRACTITIONERS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P43 AIDS 1996, Vol. 10 (Suppl. 2);S29 Don Smith*, Matthew Law†, Cassy Workman#, Alison Newman‡ Combination therapy with two, three or four agents is already widely used by high caseload GPs in Australia even though the majority of these combinations have not been evaluated in controlled clinical trials. This indicates that controlled evaluation of combination therapies will become increasingly difficult in Australia. |
| P44 | SAQUINAVIR IN THE TREATMENT OF HIV INFECTION: PATTERNS OF USE IN THE FRENCH COMPASSIONATE USE PROGRAMME, JUNE 1996. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P44 AIDS 1996, Vol. 10 (Suppl. 2);S29 Dohin E, Rousselle B, Pichot L, Loizeau S, Andriamanamihaja M, Goehrs J.M. As the first of a new class of antiretrovirals, the PI, to be made available in France for the treatment of pts with advanced HIV disease, SQV was administered predominantly as combination with ANs (99%) and as a triple therapy in 64,2% of cases. In this very advanced and heavily pretreated population, SQV demonstrated excellent safety and tolerability. These results indicate that SQV is well tolerated in combination with a variety of ANs. |
| P45 | AGGRESSIVE COMBINATION THERAPY DURING ACUTE HIV INFECTION. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P45 AIDS 1996, Vol. 10 (Suppl. 2);S30 D Rouleau B. Conway, V. Montessori, S. Fransen, S. Kwok, J. Sninsky, M. Schechter, M.V. O'Shaughnessy, J.S.G. Montaner. Our study shows that acute HIV infection is readily diagnosed in our center and antiretroviral therapy can be initiated and tolerated in many patients. Early virologic benefit of therapy is clear, with 2 patients showing undetectable viral loads over time. A controlled trial is warranted to evaluate cell and tissue viral load, as well as the optimal type and duration of therapy in these patients. |
| P46 | AN OBSERVATIONAL STUDY OF ANTIRETROVIRAL TREATMENT IN HIV-INFECTED PATIENTS ATTENDING GENERAL PRACTICES IN AUSTRALIA IN 1995 Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P46 AIDS 1996, Vol. 10 (Suppl. 2);S30 Fagan D, Phillips S, Smith DE, Duncombe C, Anderson B, Buchanan A, Roth N and the Observational Database Steering Committee. In conclusion, approximately half of the patients with HIV in this General Practice cohort who presented for treatment or review in 1995 had never been on antiretroviral treatment, and approximately a third who were entitled to treatment had not taken up this option. |
| P47 | PERIPHERAL BLOOD AND LYMPH NODE RESPONSE TO SHORT-TERM HIGH-DOSE TRIPLE COMBINATION THERAPY IN EARLY ASYMPTOMATIC HIV INFECTION Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P47 AIDS 1996, Vol. 10 (Suppl. 2);S30 Stellbrink HJ*, van Lunzen J*, Hufert F**, Zöllner B, Fenner T, Albrecht H*, Tenner-Rácz K**, Rácz P*** Early aggressive treatment leads to a marked antiviral response. Changes in PB and LN parallel each other. A self-sustained remission of HIV infection was not achieved. 3 more patients have been recruited. Updated results including all patients will be available for presentation at the conference. |
| P48 | TEMPORAL PATTERNS OF ANTIRETROVIRAL THERAPY USE IN PROVINCE WIDE DRUG TREATMENT PROGRAM Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P48 AIDS 1996, Vol. 10 (Suppl. 2);S30 Zala Carlos, Montaner JSG, Hogg RS, Yip B, Schechter MT, O'Shaughnessy M. In summary, our data demonstrates a substantial change in the use of combination antiretroviral therapy in BC over the observational period. We associate an increasing request for combination therapy with the results of major clinical studies published in the last quarter of 1995. However, the pattern of drug utilization is not fully explained by clinical efficacy data from contemporary clinical trials. |
| P49 | EARLY VERSUS DELAYED ZALCITABINE (ddC)-ZIDOVUDINE (ZDV) COMBINATION IN HIV-POSITIVE PERSONS WITH CD4 CELL COUNTS300-500/mm³: A DOUBLE-BLIND PLACEBO CONTROLLED TRIAL(ROCHE STUDY M50003). Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P49 AIDS 1996, Vol. 10 (Suppl. 2);S31 Moyle GJ#, Walker M, Harris R*, Warburg M* on behalf of the M50003 coordinating committee. Combination of ZDV/ddC as initial therapy maintains CD4 above commencement levels in a significantly greater proportion of patients than zidovudine monotherapy. In persons with CD4 >300/mm³ inclusion of ddC with ZDV does not increase the incidence of adverse events or adversely affect quality of life. |
| P50 | THERAPY WITH 3TC AND AZT IN NUCLEOSIDE ANALOGUES EXPERIENCED PATIENTS WITH ADVANCED HIV-INFECTION Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P50 AIDS 1996, Vol. 10 (Suppl. 2);S31 Löw P, Kraetsch HG, Rascu A, Grünke M, Kalden JR and Harrer T The majority of patients demonstrated clinical, immunological and virolgical benefits by combination therapy with 3TC and AZT despite extensive prior therapy with multiple nucleoside analogues. |
| P51 | TOLERABILITY AND EFFICACY OF ZDV+3TC REGIMEN IN LONGLY PRE-TREATED PATIENTS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P51 AIDS 1996, Vol. 10 (Suppl. 2);S31 Antonella d'Arminio Monforte GC Moscatelli, F Mainini, S Rusconi, L Milazzo, L Testa, L Sansone, M Mena, C Abeli, T Bini. In conclusion, the combination regimen was well tolerated and resulted in increase of CD4 counts in these patients who had already received various anti-HIV treatments and were severely immunodepressed. |
| P52 | TRIPLE-DRUG COMBINATION IN PRIMARY HIV-1 INFECTION (PHI) Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P52 AIDS 1996, Vol. 10 (Suppl. 2);S31 A. Lafeuillade*, C. Poggi**, C. Tamalet***, P. Pellegrino*, N. Profizi** This combination achieved a complete inhibilion of viral replication when administered early. Follow-up will be presented. |
| P53 | THE NEXT STEP: 4 DRUGS COMBINATION (ZDV+DDI+3TC+SAQUINAVIR) IN 10 HIV-POSITIVE PATIENTS. PRELIMINARY RESULTS ON VIROLOGIC AND IMMUNOLOGIC PARAMETERS. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P53 AIDS 1996, Vol. 10 (Suppl. 2);S32 A. Lafeuillade*, C. Farnarier**, C. Poggi*, E. Dohin***, S. Kaplanski**, G. Kaplanski**, N. Profizi*, P. Bongrand** Most patients will have completed the study period at the time of the meeting and 10 additional cases will be enrolled. |
| P54 | IMPROVEMENT IN QUALITY OF LIFE DUE TO THE USE OF RITONAVIR IN AIDS PATIENTS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P54 AIDS 1996, Vol. 10 (Suppl. 2);S32 A. Nabulsi, C. Maurath, D.Revicki, D.Conway, P. Sarocco, J. Leonard In the first 8 weeks, Ritonavir patients without AE demonstrated a slight decline in QOL, in contrast to those within AE's. By week 4, patients on ritonavir without AE's were above baseline VAS scores. By week 8, patients with AE's were back.to baseline VAS scores. Improvement for both ritonavir groups continued to week 12 and remained constant through to the end of the observation period. |
| P55 | THE USE OF EUROQOL QUALITY OF LIFE INSTRUMENT IN AIDS: RESULTS FROM TWO CLINICAL TRIALS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P55 AIDS 1996, Vol. 10 (Suppl. 2);S32 A. Nabulsi, P.Saracco, D. Revicki, D. Conway, C. Maurath, J. Leonard The EuroQol seems to be able to differentiate between symptomatic and asymptomatic AIDS patients. In addition, the instrument was responsive to health-related quality of life changes associated with the initiation of antiretroviral therapy. |
| P56 | POSTER WITHDRAWN Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P56 AIDS 1996, Vol. 10 (Suppl. 2);S32 |
| Haematology Abstracts P57 to P59, pages S32 to S33 |
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| P57 | INFLUENCE OF AZT THERAPY ON THE COUNT AND FUNCTIONAL ACTIVITY OF BLOOD PLATELETS AND ERYTHROCYTES IN HIV-INFECTED PATIENTS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P57 AIDS 1996, Vol. 10 (Suppl. 2);S32 Alexey Kravtchenko, A. Potyakova, O. Yurin, O. Astrina, V.V.Pokrovsky 3 months therapy with AZT (600 mg/d per os) did no perceptible influence on the count and functional activity of blood platelets and erythrocytes in HIV-infected patients. |
| P58 | THE USE OF GRANULOCYTE COLONY STIMULATING FACTOR IN HIV-INFECTED PATIENTS. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P58 AIDS 1996, Vol. 10 (Suppl. 2);S33 Cormican L., *Ryan M., Merry C., Mulcahy FM. Of the 12 patients on GCSF maintenance 9 successfully self-administered the agent, 1 had poor technique despite adequate training, 1 declined training and 1 was unable to self-administer due to poor vision. The cost of GCSF during the period analysed was IR£200,000. |
| P59 | FACTORS ASSOCIATED WITH HYPER-EOSINOPHILIA IN HIV INFECTION Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P59 AIDS 1996, Vol. 10 (Suppl. 2);S33 Colebunders R1,2, Van Den Eynde C1, Tala A2, Fleerackers Y2, Fonck K2, Kestens L2. The objective of this study was to identify risk factors for hypereosinophilia in HIV infected persons. |
| Interferons, Growth Factors, Cytokines, etc. Abstracts P60 to P65, pages S33 to S34 |
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| P60 | THALIDOMIDE AND KETOPROFEN REDUCE THE INCIDENCE OF ADVERSE EVENTS OF INTERLEUKIN 2 AND ENHANCE THE ANTIVIRAL ACTIVITY OF CD8 IN HIV/AIDS PATIENTS. Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P60 AIDS 1996, Vol. 10 (Suppl. 2);S33 M.Feregrino-Goyos, Gomez-Canro, W.H., Alvarado-Diez, R., Mireles Vieyra, M.P., Torras-Giner, V Thalidomide and ketroprofen reduce the incidence of Adv events and enhanced the immunological response to low doses of IL2. |
| P61 | DO ENDOGENOUS INTERFERON α LEVELS INFLUENCE THE RESPONSE TO TREATMENT WITH INTERFERON α? Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P61 AIDS 1996, Vol. 10 (Suppl. 2);S33 Mauss Stefan, Jablonowski H, Adams O*, Willers R**, Häussinger D. Combination treatment with IFN plus ZDV in this group of asymptomatic or minor symptomatic HIV+ individuals with rapidly declining CD4+ cells showed no marked effect on CD4+ cells but a modest temporary decrease of viral load lasting about 6 months. Stratification of individuals according to endogenous IFN serum levels at base-line did not reveal a marked influence of endogenous IFN on treatment outcome. |
| P62 | INTERFERON INDUCED MXA:PROTEIN AS SURROGATE MARKER IN HIV-INFECTION Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P62 AIDS 1996, Vol. 10 (Suppl. 2);S34 Mendila M., Miehlke J., Krite C., Stoll M., v. Wussow P., Schmidt R.E. MxA-protein may be a valuable parameter in assessing prognosis of HIV-positive patients. More survival data of high/low MxA-Protein positive patients are needed. MxA-protein may also be helpful in identifying patients responding to antiviral/antiretroviral therapy. The course of MxA-protein and HIV viral load during HIV-infection respectively specific treatment will be further studied. |
| P63 | DOWN REGULATION OF TNFα ACTIVITY AND INCREASE IN PLASMA LEVELS OF SOLUBLE FAS-ANTIGEN AFTER INTRAVENOUS IMMUNOGLOBULIN (NIG) ADMINISTRATION IN VIVO IN HIV-INFECTED PATIENTS ARE ASSOCIATED WITH INCREASE IN CD4+ LYMPHOCYTE COUNTS Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. P63 AIDS 1996, Vol. 10 (Suppl. 2);S34 Aukrust, P. Hestdal K, Lien E, Nordøy I, Espevik T, Möller F, Frøland SS. There was a significant Increase (approx. 40%) in CD4+ lymphocyte counts in peripheral blood 140 h after IVIG administration. Thus, IVIG infusion may downregulate abnormally increased TNF α activity and possibly "neutralize" Fas activation by increasing levels of sFas-ag, and may represent a potential immunmodulating therapeutic agent in HIV infection. |
| P64 | INTERLEUKlN (IL)-12 AND ANTI-IL-10 STIMULATE LYMPHOCYTE PROLIFERATION TO MYCOBACTERIUM AVIU |