PLENARY SESSIONS

CONCURRENT SYMPOSIA

POSTERS

Plenary Sessions
1 TREATMENT STRATEGIES IN 2000
Abstracts PL1.1 thru PL1.4, Page S1

PL1.1 PLANNING FIRST LINE (AND THEREFORE SECOND LINE) THERAPY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL1.1
AIDS 2000, Oct 22-26;14(Suppl. 4);S1
S. Hammer
When selecting the specific components of the initial regimen, practical alternatives, depending upon the strategy chosen, should already be in hand and can be assisted by drug resistance testing in the circumstance of a suboptimal response or virologic failure. As new options from both existing and new drug classes emerge, the ability to choose . . . .
PL1.2 TREATMENT FAILURE AND ITS MANAGEMENT
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL1.2
AIDS 2000, Oct 22-26;14(Suppl. 4);S1
D. Sven
Not available
PL1.3 ADHERENCE TO MEDICATION: ADHERENCE TO HIGHLY ACTIVE ANTIRETROVIRAL THERAPY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL1.3
AIDS 2000, Oct 22-26;14(Suppl. 4);S1
G. Friedland
The correlates of adherence to HIV medications have been elucidated in an array of studies and include characteristics of the patient, provider of care, regimen, disease status and clinical setting. Based upon these, many strategies for improving adherence have been proposed including assessing readiness to begin therapy, provision of information, . . . .
PL1.4 TREATMENT INTERRUPTIONS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL1.4
AIDS 2000, Oct 22-26;14(Suppl. 4);S1
B. Hirschel
Not available
PL1.5 MOMENTS OF DECISION: PATIENTS’ PERSPECTIVES
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL1.5
AIDS 2000, Oct 22-26;14(Suppl. 4);S1
F. Houyez
Not available
2 MOTHER TO CHILD TRANSMISSIONS AND THERAPEUTIC INITIATIVES IN UNDER RESOURCED COUNTRIES
Abstract PL2.1 thru PL2.4, Pages S1 to S2

PL2.1 INTERRUPTING MATERNAL-FOETAL TRANSMISSION: STATE-OF-THE-ART REVIEW
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL2.1
AIDS 2000, Oct 22-26;14(Suppl. 4);S1
H. Coovadia
A single dose of nevirapine (NVP) to the mother (during delivery) and to the newborn promises to be the simplest and most cost-effective regimen with sustained bene- ficial effect up to one year. Medium term data on the adverse affects of foetal and neonatal exposure to AZT, and short term reports on NVP, are reassuring. Breastfeeding remains the norm . . . .
PL2.2 THERAPEUTIC INITIATIVES IN THAILAND
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL2.2
AIDS 2000, Oct 22-26;14(Suppl. 4);S2
P. Phanuphak
There are several other therapeutic initiatives in Thailand. Prevention of mother-to child transmission (PMTCT) is another major activity. Several short-course AZT trials in Thailand have just been concluded. The results of these trials, as well as the Thai Red Cross donation campaign to prevent MTCT drive government’s decision to implement PMTCT nationwide. . . .
PL2.3 ANTIRETROVIRAL THERAPY: UTOPIA AND REALITY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL2.3
AIDS 2000, Oct 22-26;14(Suppl. 4);S2
P. Cahn
Not available
PL2.4 WHAT DOES IT TAKE TO PROVIDE ANTIRETROVIRAL THERAPY TO DEVELOPING COUNTRIES?
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL2.4
AIDS 2000, Oct 22-26;14(Suppl. 4);S2
J. Lange
Not available
3 ANTIVIRAL THERAPY IN DIFFERENT POPULATIONS
Abstract PL3.1 thru PL3.7, Pages S2 to S4

PL3.1 ANTIVIRAL THERAPY IN CHILDREN: REVIEW OF THE ISSUES
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL3.1
AIDS 2000, Oct 22-26;14(Suppl. 4);S2
C. Giaquinto
Not available
PL3.2 ANTIVIRAL THERAPY IN WOMEN
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL3.2
AIDS 2000, Oct 22-26;14(Suppl. 4);S2
D. Mercey
Not available
PL3.3 ANTIVIRAL THERAPY AND MANAGEMENT OF HIV IN INTRAVENOUS DRUG USERS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL3.3
AIDS 2000, Oct 22-26;14(Suppl. 4);S2
F. Mulcahy
The management of HIV infection is therefore both complex and challenging. Options include linking ART with daily observed methadone maintenance therapy, choosing simple once or twice daily regimens anticipating and treating drug interactions and consistent patient evaluation at combined addiction/ medical trials.
PL3.4 VIRAL LOAD CHANGES IN RESPONSE TO ANTIRETROVIRAL THERAPY ACCORDING TO THE BASELINE CD4 LYMPHOCYTE COUNT AND VIRAL LOAD
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL3.4
AIDS 2000, Oct 22-26;14(Suppl. 4);S3
A.N. Phillips, S. Staszewski, R.Weber, O. Kirk, P. Francioli, V. Miller, P. Vernazza, J. Lundgren and B. Ledergerber on behalf of the Swiss HIV Cohort Study, the Frankfurt HIV Clinic Cohort and the EuroSIDA Study Group
Precise characterization of the relationship between baseline CD4 count/viral load and viral load response would provide information for the decision of when to initiate antiretroviral therapy. We studied 2742 therapy-naïve individuals from three clinic-based cohort studies who initiated antiretroviral therapy in 1996 or after and have been followed for a median . . . .
PL3.5 WHEN TO START HAART IN CHRONICALLY HIV-INFECTED PATIENTS? A COLLECTION OF PIECES OF EVIDENCE FROM THE I.CO.N.A. STUDY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL3.5
AIDS 2000, Oct 22-26;14(Suppl. 4);S3
A. Cozzi Lepri1, A.N. Phillips1, A. d’ Arminio Monforte2, S. Muro2, A. De Luca2, P. Pezzotti2, P. Vigano 2, A. Orani2, S. d’ Elia 2 and M. Moroni2
This non-randomised study could only address some aspects related to the issue of when to start HAART in asymptomatic infection. However, our data show no clear immunological or virological advantage in starting HAART at a CD4 count > 350 rather than starting when CD4 count ranges between 200 and 350. They also confirm that CD4 count rises are clinically meaningful, in that they are associated with reduced risk of AIDS and death.
PL3.6 PLASMA AND TISSUE HIV-1 AND HIV-2 VIRAL LOAD IN HIV-2 AND DUAL HIV-1/HIV-2 INFECTED INDIVIDUALS: IMPLICATIONS FOR STARTING HAART
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL3.6
AIDS 2000, Oct 22-26;14(Suppl. 4);S3
M. Schutten, M.E. van der Ende, K. Tenner-Racz, P. Racz, H.G.M. Niesters and A.D.M.E. Osterhaus
On basis of these results and the limited options for treating HIV-2 (inadequate efficacy of NNRTIs and most probably also nelfinavir and amprenavir) we recommend starting ART as late as possible (CD4+ cells < 300/µl or plasma HIV-2 RNA levels > 5000 copies/ml). The fact that both HIV-1 and HIV-2 may actively replicate in dual HIV-1/HIV-2+ individuals also indicate that it is wise to refrain from treating such individuals with antivirals that are not efficacious against HIV-2.
PL3.7 COMPLIANCE IS SIGNIFICANTLY BETTER IN HAART RESPONDERS COMPARED TO NON-RESPONDERS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL3.7
AIDS 2000, Oct 22-26;14(Suppl. 4);S3
A.-M. Vandamme1, K. Van Vaerenbergh1, A. Deschamps1, V. De Graeve1, V. De Saar1, B. Maes1, H. Ceunen1, K. De Smet2, W. Peetermans1, H. Bobbaers1, M. Van Ranst1, J. Desmyter1, E. De Clercq1, E. Van Wijngaerden1 and S. De Geest1
Perfectly compliant patients can control virus replication for a prolonged period, even in the presence of baseline resistance mutations. The patients that had a poor response to HAART were also those with a signifi- cantly lower compliance. In our patient population, reduced compliance resulted in therapy failure, mostly associated with a build-up of resistance mutations.
4 RESISTANCE
Abstract PL4.1 thru PL4.5, Pages S4 to S4

PL4.1 OVERVIEW ON THE LATEST ON GENOTYPE/PHENOTYPE AND REPLICATIVE FITNESS: THE SCIENCE
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL4.1
AIDS 2000, Oct 22-26;14(Suppl. 4);S4
D.D. Richman
Data to partially address each of these questions have been generated. Defining what is not adequately answered will help direct more effective clinical research.
PL4.2 THE VALUE AND LIMITATIONS OF RESISTANCE TESTING AND HOW BEST TO USE IT: PRACTICALITIES FOR THE PHYSICIAN
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL4.2
AIDS 2000, Oct 22-26;14(Suppl. 4);S4
V. Miller
Not available
PL4.3 THE TRANSMISSION OF RESISTANT VIRUSES AND IMPLICATIONS FOR THERAPY AND OUTCOME
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL4.3
AIDS 2000, Oct 22-26;14(Suppl. 4);S4
L. Perrin
Not available
PL4.4 PERSISTENCE OF HIV-1 REPLICATION AND GENOTYPIC RESISTANCE IN SANCTUARY SITES AFTER 3 YEARS OF EFFECTIVE HAART: RELEVANCE OF PROTEASE INHIBITORS DIFFUSION
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL4.4
AIDS 2000, Oct 22-26;14(Suppl. 4);S4
A. Lafeuillade1, C. Solas2, G. Hittinger1, S. Chadapaud1, H. Khiri3, P. Halfon3, B. Lacarelle2
A large inter-individual variability of IDV and NFV concentrations was found in the different sanctuary sites. Residual viral replication and resistance appear to be related with PIs diffusion in semen but not in CSF and lymph nodes.
PL4.5 R165335–TMC125, A NOVEL NON NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NNRTI) WITH NANOMOLAR ACTIVITY AGAINST NNRTI RESISTANT HIV STRAINS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL4.5
AIDS 2000, Oct 22-26;14(Suppl. 4);S4
K. Andries1, M.-P. de Béthune2, D.W. Ludovici3, M.J. Kukla3, H. Azijn2, P. Lewi4, P.A.J. Janssen4 and R. Pauwels2
Evaluation of > 300 triazine and pyrimidine analogues of a lead molecule led to the identification of a series of compounds active in the nanomolar range against both wt and resistant strains. R165335–TMC125, a diaminopyrimidine (DAPY) derivative, had the best antiviral potency profile. . . .
5 INFECTIONS AND TUMOURS
Abstract PL5.1 thru PL5.6, Pages S5 to S6

PL5.1 OPPORTUNISTIC INFECTIONS: WHAT’S NEW?
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL5.1
AIDS 2000, Oct 22-26;14(Suppl. 4);S5
H. Furrer
New recommendations on prophylaxis and maintenance therapy: Taking into account the decreased risk of OIs in patients on ART, new recommendations about discontinuation of prophylaxis and maintenance therapy seem warranted. Numerous studies addressing the safety of discontinuation are being performed. . . .
PL5.2 HIV AND HEPATITIS – HBV AND HCV
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL5.2
AIDS 2000, Oct 22-26;14(Suppl. 4);S5
A. Hatzakis
Not available
PL5.3 KAPOSI’S SARCOMA HERPESVIRUS: FROM CELL BIOLOGY TO PATHOGENESIS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL5.3
AIDS 2000, Oct 22-26;14(Suppl. 4);S5
C. Boshoff
Kaposi’s sarcoma lesions can resolve with partial restoration of the immune system, i.e. post-transplantation KS resolves when immunosuppression is stopped and AIDS-KS often improves with HAART. This suggests that cytotoxic T cell (CTL) responses against KSHV might be important in the pathogenesis of KS. The identification of CTLs against this virus will be discussed.
PL5.4.1 EFFICACY OF THE REGENERATING IMMUNE SYSTEM IN THE INHIBITION OF CMV REPLICATION AFTER HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART))
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL5.4.1
AIDS 2000, Oct 22-26;14(Suppl. 4);S5
J.R. Deayton, C.A. Sabin, M.A. Johnson, P.D. Griffiths, V.C. Emery
The calculated mean antiviral efficacy of the regenerating immune system of 61.5% may be compared to that of ganciclovir which has a mean efficacy of 91.5% against wild type CMV. This further explains the protective effect of HAART against CMV disease, even in patients with high CMV loads at baseline. The half-life of decline of CMV DNA in blood after HAART is variable. . . .
PL5.4.2 RECURRENCE OF CMV VIRAEMIA AND DEVELOPMENT OF ANTI-CMV DRUG RESISTANCE IN PATIENTS RECEIVING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY AFTER CMV RETINITIS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL5.4.2
AIDS 2000, Oct 22-26;14(Suppl. 4);S5
J.R. Deayton, C. Shannon-Lowe, P. Wilson, M.A. Johnson, P.D. Griffiths, V.C. Emery
Patients who have received HAART and have extended survival rates following CMV retinitis (CMVR) have now had prolonged exposure to anti-CMV therapies. This study aims to identify risk factors for recurrence of CMV viraemia in such patients and to investigate the development of ganciclovir resistance associated with the long term receipt of maintenance therapy for CMVR.
PL5.5 THE CORRELATION BETWEEN THE DEVELOPMENT OF CYTOMEGALOVIRUS RETINITIS AND THE CYTOMEGALOVIRUS-SPECIFIC IMMUNOLOGIC REACTIVITY OF T-CELLS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL5.5
AIDS 2000, Oct 22-26;14(Suppl. 4);S6
Sung-Chin Pan, Szu-Min Hsieh, Chien-Ching Hung, Hsing-Chun Tsai, Mao-Yuan Chen and Shan-Chwen Chang
Thus, the development of CR may be associated with poor reactivity of CD4+ T-cells, but not with that of CD8+ T-cells, against CMV. Post-HAART CR may be due to poorly reconstituted immune response to CMV, rather than immune rebound. This evaluation of CMV-specific immune reactivity may help select high-risk patients who may benefit from pre-emptive CMV therapy.
6 NOVEL ASPECTS OF INFECTION AND TREATMENT
Abstract PL6.1 thru PL6.6, Pages S6 to S8

PL6.1 POST-EXPOSURE PROPHYLAXIS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL6.1
AIDS 2000, Oct 22-26;14(Suppl. 4);S6
D. Henderson
Not available
PL6.2 INFECTIVITY AND SEXUAL TRANSMISSION
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL6.2
AIDS 2000, Oct 22-26;14(Suppl. 4);S6
P.L. Vernazza
Antiretroviral therapy significantly reduces the genital shedding of HIV, i.e. the viral inoculum. There is limited information about this effect of therapy on HIV incidence but intuitively, any reduction of the inoculum size must result in lower risk of transmission, as has been demonstrated for the case of vertical transmission. . . .
PL6.3 TENOFOVIR DISOPROXIL FUMARATE (TDF) FOR THE TREATMENT OF ANTIRETROVIRAL EXPERIENCED PATIENTS: A 48 WEEK ANALYSIS OF A RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED STUDY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL6.3
AIDS 2000, Oct 22-26;14(Suppl. 4);S6
R. Schooley1, P. Ruane2, R. Myers3, G. Beall4, H. Lampiris5, D. Berger6, M. Miller7, A. Cheng7, R. Mills7 and I. McGowan7 for the Study 902 Team
Tenofovir DF is a once daily nucleotide analogue reverse transcriptase (RT) inhibitor with potent activity against wild type and nucleoside resistant HIV. Patients with HIV RNA between 400 and 100 000 copies/ml were randomized 2 : 2 : 2 : 1 in a blinded fashion to receive 75 150 or 300 mg of TDF or placebo in addition to their stable antiretroviral therapy (ART) at 22 sites. . . .
PL6.4 A NOVEL USE OF ABACAVIR TO SIMPLIFY THERAPY AND REDUCE LONG-TERM TOXICITY IN PI-EXPERIENCED PATIENTS SUCCESSFULLY TREATED WITH HAART: 48-WEEK RESULTS (CNA30017)
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL6.4
AIDS 2000, Oct 22-26;14(Suppl. 4);S7
M. Youle for the CNA30017 study team
These data demonstrate sustained virological suppression following a switch from PI-containing HAART to simplified, ABC-based triple nucleoside therapy, with a trend to lower triglyceride and cholesterol and increased treatment satisfaction. Viral rebound following switch to ABC was associated with single mutations only, which would allow many salvage options.
PL6.5 ABT-378/RITONAVIR (ABT-378/r) VERSUS NELFINAVIR IN ANTIRETROVIRAL NAÏVE SUBJECTS: WEEK 48 COMPARISON IN A PHASE III BLINDED RANDOMIZED CLINICAL TRIAL
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL6.5
AIDS 2000, Oct 22-26;14(Suppl. 4);S7
M. Johnson1, G. Beall2, A. Badley3, W. Cameron3, D. Johnson4, P. Ruane5, R. Rubio6, R. Stryker7, S. Walmsley8, M. King9, P. Cernohous9, J. Moseley9, M. Opferman9, M. Sattler9, B. Bernstein9, and E. Sun9 for the M98–863 Study Team
A significantly greater proportion of ABT-378/r treated subjects achieved HIV RNA below the LOQ in all analyses at Weeks 40 and 48. Both regimens were well tolerated, as manifested by the low incidence of study drug-related discontinuations through week 40.
PL6.6 BMS-232632 - CLINICAL TRIAL AI424–007: SAFETY, EFFICACY OF A ONCE DAILY PROTEASE INHIBITOR AT 24 WEEKS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL6.6
AIDS 2000, Oct 22-26;14(Suppl. 4);S7
P.J. Piliero1, I.M. Sanne2, R. Wood3, T. Kellher4, A. Mongillo4, A. Cross4, S. Schnittman 4 and M. Giordano4
In conclusion, results at the 24-week (stage I) evaluation in trial AI424– 007 support this potent PI as a component of combination therapy due to its efficacy, safety and tolerability, and once daily dosing.
PL6.7 CONTINUED INDINAVIR (800 MG TID) VERSUS SWITCHING TO INDINAVIR + RITONAVIR (800/100 MG BID) IN HIV PATIENTS HAVING ACHIEVED VIRAL LOAD SUPPRESSION. A RANDOMIZED STUDY: THE BID EFFICACY AND SAFETY TRIAL (BEST)
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL6.7
AIDS 2000, Oct 22-26;14(Suppl. 4);S8
D. Podzamczer1, J. Arrizabalaga2, P. Van Wanzeele3, M. Harris4, C. Pedersen5, P. Cahn6, A. Casiro7, F. Chiodo8, J.A. Arnaiz9 and J.M. Gatell9 for the BEST Study Team
These preliminary data suggest that bid administration of IDV 800 mg in combination with RTV 100 mg is generally well tolerated and maintains comparable viral suppression in stable HIV-infected patients in comparison with the standard tid regimen.
PL6.8 A RANDOMISED TRIAL EVALUATING THREE NRTI REGIMENS WITH AND WITHOUT NELFINAVIR IN HIV-INFECTED CHILDREN: 48-WEEK FOLLOW-UP FROM THE PENTA 5 TRIAL
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL6.8
AIDS 2000, Oct 22-26;14(Suppl. 4);S8
D.M. Gibb for the PENTA 5 Executive and the PENTA Steering Committees
The ABC-containing arms were well generally tolerated and resulted in the greatest reduction in VL. There were no serious concerns about NFV toxicity.
7 HARNESSING THE IMMUNE RESPONSE
Abstract PL7.1 thru PL7.6, Pages S8 to S9

PL7.1 WHAT ARE THE DIFFERENCES IN IMMUNE RESTORATION IN RESPONSE TO HAART AT DIFFERENT LEVELS OF IMMUNE SUPPRESSION/IMMUNODEFICIENCY AT INITIATION OF TREATMENT AND DO THEY MATTER?
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL7.1
AIDS 2000, Oct 22-26;14(Suppl. 4);S8
C. Lane
Not available
PL7.2 IMMUNE BASED THERAPY AND THERAPEUTIC VACCINES
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL7.2
AIDS 2000, Oct 22-26;14(Suppl. 4);S9
G. Pantaleo
Not available
PL7.3 INDUCTION OF PROTECTIVE IMMUNITY AGAINST HIV/AIDS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL7.3
AIDS 2000, Oct 22-26;14(Suppl. 4);S9
M. Girard
. . . .the first phase III efficacy trials with a bivalent gp120 subunit vaccine have been initiated last year in the USA with clade B antigens and in Thailand with a mixture of clade B and clade E antigens. In spite of such progress, the development of a simple vaccine capable of inducing cross-neutralizing antibodies against primary virus isolates and broad polyepitopic CD8+ T-cell responses in a majority of vaccinees still remains an elusive challenge.
PL7.4 FUNCTIONAL SIGNIFICANCE OF CD4 CELL NUMBERS ON THE WAY DOWN VERSUS ON THE WAY UP
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL7.4
AIDS 2000, Oct 22-26;14(Suppl. 4);S9
M.M. Lederman, H. Valdez, K. Medvik, D. Dorazio, R. Asaad, C. Pacheko and J. Sierra-Vladero
CD4 cell numbers do not necessarily reflect the repertoire of CD4 cell recognition in treated and untreated HIV infection. While selected responses are well restored after suppression of HIV replication, others are not and this may reflect exposure to antigen and targeted effects of HIV replication on cell function.
PL7.5 A RANDOMIZED CONTROLLED PHASE II STUDY OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) WITH INTERMITTENT INTERLEUKIN-2 (IL-2) BY CONTINUOUS IV (CIV) OR SUBCUTANEOUS (SC) ROUTES IN HIV-INFECTED PATIENTS WITH CD4+ COUNTS 50–350 CELLS/MM³: ACTG 328-RESULTS AT 60 WEEKS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL7.5
AIDS 2000, Oct 22-26;14(Suppl. 4);S9
R. Mitsuyasu, R. Pollard, R. Gelman, D.Weng for the ACTG 328 protocol team
Significant increases in CD4+ counts were seen with both CIV and SC IL-2 compared to HAART alone after 60 weeks of therapy. IL-2 did not appear to increase or decrease the proportion of patients with plasma RNA < 50 copies/ml after 60 weeks of initial HAART therapy. An early trend to somewhat lower occurrence of AIDS-defining illnesses was observed in IL-2 treated patients, although the study was not designed to detect this difference. Additional clinical and immunologic and virologic follow-up of these patients is in progress.
PL7.6 CONTINUED LOW MORBIDITY AND MORTALITY AMONG PATIENTS WITH ADVANCED HIV INFECTION AND THEIR PATTERNS OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) USAGE
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL7.6
AIDS 2000, Oct 22-26;14(Suppl. 4);S9
F. Palella
Not available
8 PHARMACOLOGY AND THERAPEUTIC DRUG MONITORING
Abstract PL8.1 thru PL8.7, Pages S10 to S11
PL8.1 KEY PHARMACOLOGICAL ISSUES IN HIV THERAPY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL8.1
AIDS 2000, Oct 22-26;14(Suppl. 4);S10
D. Back
Finally if we are to understand the complex mechanisms of mitochondrial toxicity or drug hypersensitivity which have emerged as concerns for HIV therapy then basic and clinical pharmacology must be part of the armamentarium to tackle these and related issues.
PL8.2 THERAPEUTIC DRUG MONITORING
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL8.2
AIDS 2000, Oct 22-26;14(Suppl. 4);S10
D.M. Burger
Based on the above arguments, TDM, especially for the protease inhibitors, appears indicated. Some argue that controlled clinical trials need to demonstrate a clinical benefit of TDM before it can be recommended as standard care, while others already use it in their routine patient management. Pros and cons of TDM will be discussed.
PL8.3 DRUG INTERACTIONS - WHICH ONES ARE CLINICALLY IMPORTANT?
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL8.3
AIDS 2000, Oct 22-26;14(Suppl. 4);S10
R. Hoetelmans
Not available
PL8.4 MEASUREMENT OF NUCLEOSIDE ANALOGUE TRIPHOSPHATES BY ENZYMATIC ASSAY IN HIV PATIENTS IN A CLINICAL SETTING
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL8.4
AIDS 2000, Oct 22-26;14(Suppl. 4);S10
P.G. Hoggard1, S. Kewn1, S.D. Sales1, J. Lloyd1, B. Maher1, S.H. Khoo1, E.Wilkins2, T. Jones3, D. Pillay4, C. Sabin5 and D.J. Back1
These data illustrate the importance of determining drug triphosphate/ dNTP ratios in HIV-positive patients.
PL8.5 NEVIRAPINE-INDUCED LIVER TOXICITY: A PROSPECTIVE COHORT STUDY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL8.5
AIDS 2000, Oct 22-26;14(Suppl. 4);S11
E. Martínez1, J.A. Arnaiz2, A. Cruceta1, J.B. Pérez-Cuevas1, A. Mocroft3, X. Carné2 and J.M. Gatell1
NVP was generally well tolerated. Clinical hepatitis seldom appeared and other underlying factors might be related. Abnormalities in ALAT or ASAT increased steadily along first year of therapy, but they were mainly asymptomatic. LFT monitoring during first 1–2 months of therapy does not seem to be justified.
PL8.6 HEPATIC SAFETY WITH NEVIRAPINE (NVP) AND TWO NUCLEOSIDES IN PATIENTS WITH ADVANCED HIV INFECTION, FROM A PLACEBO (PBO) CONTROLLED CLINICAL ENDPOINT TRIAL (1090)
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL8.6
AIDS 2000, Oct 22-26;14(Suppl. 4);S11
P. Cahn1, M. Johnson2, R. Nusrat3, D. Hall3, P. Robinson3 and the 31090 Study Team
Hepatic events are encountered in HIV-infected patients taking NVP and non-NVP containing regimens. Understanding potential risk factors and clinically appropriate caution should help to minimize important HEs in patients receiving combination antiretroviral therapy.
PL8.7 REDUCED BONE MINERAL DENSITY IN HIV POSITIVE INDIVIDUALS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL8.7
AIDS 2000, Oct 22-26;14(Suppl. 4);S11
A.L. Moore, A, Vashist1, A. Mocroft, A.N. Phillips, J. Studd1 and M.A. Johnson
The prevalence of reduced bone density in this HIV positive population is high and our results suggest evidence of an association with use of antiretroviral treatment. Further analysis, particularly of different treatment regimens, on a larger sample is ongoing.
9 LATE BREAKERS
Abstract PL9.1 thru PL9.7, Pages S12 to S13
PL9.1 ACTIVITY OF CYCLOSPORIN A IN COMBINATION WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY IN PRIMARY HIV-1 INFECTION
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL9.1
AIDS 2000, Oct 22-26;14(Suppl. 4);S12
G.P. Rizzardi1, B. Capiluppi2, J.P. Chave3, G. Tambussi2, P. Champagne1, A. Harrari1, P.A. Bart1, A. Lazzarin2 and G. Pantaleo1
Not available
PL9.2 PREVENTION OF NEVIRAPINE-ASSOCIATED EXANTHEMA USING SLOW DOSE ESCALATION, ANTIHISTAMINICS OR CORTICOSTEROIDS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL9.2
AIDS 2000, Oct 22-26;14(Suppl. 4);S12
P. Barreiro, V. Soriano, E. Casas2, M. Tellez1, V. Estrada1, R. Hoetelmans3, I. Jiménez-Nácher4 and J. González-Lahoz
In conclusion, the incidence of rash complicating the first few weeks of treatment with NVP can be diminished adding corticosteroids or antihistaminics for two weeks to the standard recommendation, or using a slow escalating dosing. This third approach is proven to be pharmacokinetically safe.
PL9.3 SEVERE LIVER TOXICITY IN PATIENTS RECEIVING TWO NUCLEOSIDE ANALOGUES AND A NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL9.3
AIDS 2000, Oct 22-26;14(Suppl. 4);S12
I. Sanne on behalf of the FTC-302 Study Investigators and the FTC-302 Independent Clinical Steering Committee
In this study, a high incidence of severe liver toxicity was observed, especially in women. Clinically these events were attributed to NVP in combination with d4T and blinded treatment medication. Consistent with recent recommendations, liver enzymes in patients receiving NVP with other antiretrovirals should be monitored closely, particularly during the first 8 weeks of use.
PL9.4 THE CTROUGH INHIBITORY QUOTIENT PREDICTS VIROLOGIC RESPONSE TO ABT-378/RITONAVIR (ABT-378/R) THERAPY IN TREATMENT-EXPERIENCED PATIENTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL9.4
AIDS 2000, Oct 22-26;14(Suppl. 4);S12
A. Hsu, G.R. Granneman, D.J. Kempf, J. Isaacson, M. King, S. Brun, B. Bernstein and E. Sun
This analysis demonstrates that IQ:Ctrough, which accounts for drug exposure as well as viral susceptibility, can be used to estimate antiviral activity in patients with reduced susceptibility. In contrast, PK parameters alone appear to be inadequate for assessing antiviral activity of PIs in vivo, particularly in previously treated patients.
PL9.5 USE OF NEURAL NETWORKS TO DEFINE THE GENETIC BASIS OF HIV-1 RESISTANCE TO D4T
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL9.5
AIDS 2000, Oct 22-26;14(Suppl. 4);S12
B.A. Larder and D.Wang
In conclusion, these results show that at least 26 RT mutations may play a role in d4T resistance, including AZT resistance mutations. Refinement of these models should further enhance our understanding of the genetic basis of d4T phenotypic resistance.
PL9.6 TRANSMISSION AND FITNESS OF DRUG RESISTANT STRAINS OF HIV
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL9.6
AIDS 2000, Oct 22-26;14(Suppl. 4);S13
A.J. Leigh Brown, S.D.W. Frost, J.M. Whitcomb, A.R. McLean, N.S. Hellmann, C.S. Leen, R.P. Brettle, D.V. Havlir, W.C. Mathews, D.D. Richman and S.J. Little
Genotypic data from 111 individuals with primary HIV infection who had not received antiretroviral therapy revealed nine bearing mutations at primary resistance-associated amino acids in RT. The probable frequency of transmission of drug resistant strains in this group is therefore 9/111 = 8%. Defining ‘potential transmitters’ as individuals with plasma viral load (pVL) > 1500 copies/ml yields an estimate of 33% for the proportion of potential transmitters . . . .
10 ADVERSE EVENTS OF THERAPY
Abstract PL10.1 thru PL10.7, Pages S13 to S14
PL10-1 A PERSPECTIVE ON THE ADVERSE EVENTS OF HAART: AN OVERVIEW TO INCLUDE LIPODYSTROPHY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL10-1
AIDS 2000, Oct 22-26;14(Suppl. 4);S13
D. Cooper
Not available
PL10-2 PATHOGENESIS OF LIPODYSTROPHY AND METABOLIC DISORDERS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL10-2
AIDS 2000, Oct 22-26;14(Suppl. 4);S13
M. Schambelan
Not available
PL10-3 LIPODYSTROPHY SYNDROME: DEVELOPING A CASE DEFINITION
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL10-3
AIDS 2000, Oct 22-26;14(Suppl. 4);S13
A. Carr
Under the auspices of the EMEA, an industry-sponsored study has begun in 37 sites worldwide that will endeavour to generate a valid, simple and broadly applicable case definition. The case-control approach developed by the American Rheumatology Association over the last 30 years for the diagnosis of a large number of rheumatic diseases has been adopted and will be discussed, along with the study outline.
PL10-4 MANAGEMENT OF LIPODYSTROPHY AND METABOLIC DISORDERS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL10-4
AIDS 2000, Oct 22-26;14(Suppl. 4);S13
F. Goebel
In a variety of uncontrolled or randomised switch studies substituting PIs or d4T with NNRTIs or other NRTIs most resulted in improvement of lipids, insulin sensitivity and reduction of visceral fat. Reconstitution of subcutaneous fat tissue was rarely observed within 6–12 months. Recent reports on altered cytokine pattern (e.g. TNFα) might justify cytokine changing treatment studies.
PL10-5 THE PHYSICAL AND PSYCHOLOGICAL MANAGEMENT OF LIPODYSTROPHY AND METABOLIC ABNORMALITIES: A PATIENT’S PERSPECTIVE
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL10-5
AIDS 2000, Oct 22-26;14(Suppl. 4);S14
Dawn Averitt
This presentation will address the complex issues, both physical and psychological, associated with the fat maldistribution and dismorphia (commonly referred to as lipodystrophy) from the perspective of a woman living with AIDS. In addition, the presenter will share several case studies to illustrate the deleterious effect of these abnormalities on quality of life, adherence, and treatment initiation.
CONCURRENT SYMPOSIA
CS3 NEW THERAPEUTIC OPTIONS IN A NEW CENTURY
Abstracts CS3.1 thru CS3.6, Page S15 TO S16

CS3.1 OVERVIEW OF PROTEASE INHIBITOR SUBSTITUTION STUDIES
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. CS3-1
AIDS 2000, Oct 22-26;14(Suppl. 4);S15
R. L. Murphy
Patients on highly active antiretroviral therapy have many treatment options. When protease inhibitor toxicities are suspected, a switch to an alternative regimen consisting of a non-nucleoside plus two nucleosides or of triple nucleosides can be considered effective but is not without modest risk.
CS3-2 PRELIMINARY RESULTS OF A RANDOMISED, OPEN, MULTICENTRE TRIAL COMPARING COMBIVIR PLUS NELFINAVIR OR NEVIRAPINE IN HIV-INFECTED NAÏVE PATIENTS (THE COMBINE STUDY)
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. CS3-2
AIDS 2000, Oct 22-26;14(Suppl. 4);S15
D. Podzamczer on behalf of the Combine Study Team
No differences in the reduction of VL in samples of lymphoid tissue, CSF and semen were observed between both regimens in a subgroup of patients. In conclusion, these preliminary results suggested that CNr may have greater efficacy than CNf. Both regimens have an acceptable tolerance profile.
CS3-3 EMERGING ISSUES IN NNRTI THERAPY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. CS3-3
AIDS 2000, Oct 22-26;14(Suppl. 4);S15
J. Montaner
Data from a clinical endpoint study involving approximately 2000 patients with advanced HIV disease have demonstrated the efficacy of nevirapine/ZDV/3TC in patients with high plasma viral loads. They have also provided valuable insights into the safety profile of nevirapine which will be discussed. NNRTI-based regimens provide a valuable treatment option at all stages of HIV disease, provided that they are used in an optimal manner.
CS3-4 PERSPECTIVES ON THE SAFETY PROFILES OF ANTIRETROVIRAL DRUGS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. CS4-4
AIDS 2000, Oct 22-26;14(Suppl. 4);S16
J.M.A. Lange
Acute NNRTI toxicity, such as rash, presents during the first weeks of therapy. Vigilance during this predictable period and adherence to empirically formulated rash-management guidelines prevent deterioration to more severe syndromes. Management of chronic toxicity associated with PIs and nRTIs is hampered by their lack of predictability and lack of prophylactic and therapeutic measures (except for nRTI withdrawal in the case of mitochondrial toxicity). . . .
CS3-5 HIVNET 012 - FINAL RESULTS AND IMPLEMENTATION PROGRAMME
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. CS3-5
AIDS 2000, Oct 22-26;14(Suppl. 4);S16
M. Owor
Study results indicate that a single dose of NVP given to HIV+ women in labour and to the newborn within 72h of birth is safe and significantly reduces mother-to-child HIV transmission compared with a short course AZT regimen. This reduction is sustained to 12 months in a breastfeeding population.
CS3-6 TIPRANAVIR – THE PROTEASE INHIBITOR FOR THE 21ST CENTURY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. CS3-6
AIDS 2000, Oct 22-26;14(Suppl. 4);S16
R. Wood
Tipranavir is a novel protease inhibitor with in vitro activity against resistant HIV-1 isolates. When combined with low dose ritonavir, it is well tolerated and results in plasma tipranavir trough levels well above the corrected IC90 for HIV inhibition.
POSTERS

1.1 NEW ANTIRETROVIRALS
Abstracts P1 thru P14, Page S17 TO S21

P1 EFFICIENCY OF MYELOPEPTIDES (MYELOPID) ADMINISTERING TO HIV PATIENTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P1
AIDS 2000, Oct 22-26;14(Suppl. 4);S17
E.T. Taleb, L.P. Siziakina, A.A. Mikhailova, I.L. Docucina
Not available
P2 R165335–TMC125, A THIRD GENERATION NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NNRTI), INHIBITS 97% OF MORE THAN 1000 RECOMBINANT NNRTI RESISTANT HIV CLINICAL ISOLATES WITH AN IC50 BELOW 100 NM
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P2
AIDS 2000, Oct 22-26;14(Suppl. 4);S17
M.-P. de Béthune1, K. Hertogs2, H. Azijn1, B. Larder3, K. Andries4, P.A.J. Janssen5 and R. Pauwels1
Because of its potency against a vast majority of recent NNRTI resistant HIV clinical isolates, R165335–TMC125 belongs to the third generation of NNRTIs. Its superior in vitro resistance profile makes R165335–TMC125 an excellent candidate for further clinical development.
P3 THE FIRST EXPERIENCE OF HAART WITH PHOSPHAZID + DIDANOSINE + NEVIRAPIN IN HIV-INFECTED PATIENTS IN RUSSIA
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P3
AIDS 2000, Oct 22-26;14(Suppl. 4);S17
A.V. Kravtchenko, G.G. Salamov, L.V. Serebrovskaya, E.V. Bogoslovskaya, O.G. Sergienko and V.V. Pokrovsky
Preliminary results: after 12 weeks of therapy with PhAZT+ddI+NVP viral load decreased on l.6 Log10. 64% patients had RNA HIV lower than 400 eqc/ml. The count of CD4 cells and CD4/8 ratio significantly increased. The treatment was well-tolerated. We observed only one case of allergic rash associated with nevirapin (after 1 month of therapy) due to that treatment was stopped. We registered decreasing the count of RBC in 1/3 patients. Mean level of ALT changed not significantly. Now the study is still ongoing.
P4 AN INITIAL SAFETY AND EFFICACY CLINICAL TRIAL OF GPG–NH2, A TRIPEPTIDE WITH A NEW ANTIRETROVIRAL MODE OF ACTION
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P4
AIDS 2000, Oct 22-26;14(Suppl. 4);S17
P.O. Pehrson1,2, A. Sönnerborg 1,2, A. Vahlne3 and J. Spira3
GPN–NH2 has a completely new mode of antiviral activity and hence represents an additional drug alternative to existing therapies, especially for patients with incomplete antiviral response. Further studies will be performed to evaluate the clinical utility of GPG–NH2.
P5 ANTI-HIV ACTIVITY OF DAPD MONOTHERAPY IN TREATMENT-NAÏVE AND TREATMENT-EXPERIENCED SUBJECTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P5
AIDS 2000, Oct 22-26;14(Suppl. 4);S18
F. Raffi1 , H. Kessler, M. Thompson, J. Eron, J. Jacobson, R. Arduino, F. Torriani, S. Deeks, D. Sereni, N. Sista, J. Harris, R. DeMasi, J. Bigley and F. Rousseau
These results suggest a dose-dependent clinical antiviral activity of DAPD in treatment-naïve patients, encouraging activity in heavily pretreated subjects, good short-term tolerability profile, and the absence of resistance mutations in a 15-day monotherapy study. These data warrant further clinical development of this novel molecule.
P6 SAFETY, TOLERABILITY AND ANTIVIRAL PHARMACODYNAMICS OF PEGYLATED INTERFERON-α2B IN HIV-1 INFECTION: A PHASE I STUDY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P6
AIDS 2000, Oct 22-26;14(Suppl. 4);S18
A. Hatzakis1, M. Laughlin2, P. Gargalianos3, M. Lazanas4, C. Botsi5, G. Saroglou6 and P. Glue2
In conclusion, PEG-intron up to the dose of 3.0 μg/kg is well tolerated as 4-week monotherapy with a significant inhibitory effect against HIV-1 in vivo.
P7 HIV-1 DYNAMICS IN VIVO AFTER ADMINISTRATION OF PEGYLATED INTERFERON-α-2B (PEG-INTRON)
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P7
AIDS 2000, Oct 22-26;14(Suppl. 4);S18
V. Sypsa1, M. Laughlin2, P. Gargalianos3, M. Lazanas4, C. Botsi5, G. Saroglou6, C. Anastassopoulou1, H. Sabatakou3, N. Magafas4, N. Stavrianeas5, P. Giannakopoulou6, P. Glue2 and A. Hatzakis1
In conclusion, antiviral efficacy was associated with baseline immunological parameters and with PEG-intron dose at the lower doses with a plateau effect above 1.5 μg/kg.
P8 IMMUNOLOGIC PROFILE OF HIV-1 INFECTED PATIENTS AFTER ADMINISTRATION OF PEGYLATED INTERFERON-α-2b (PEG-INTRON)
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P8
AIDS 2000, Oct 22-26;14(Suppl. 4);S19
V. Vigklis1,3, M. Laughlin2, P. Gargalianos3, M. Lazanas4, C. Botsi5, G. Saroglou6, H. Sabatakou3, D. Paraskeva4, N. Stavrianeas5, N. Mavroidi6, P. Glue2 and A. Hatzakis1
The increasing pattern of CD4 and the decline of CD8 and immune activation markers is consistent with data obtained from PI’s monotherapy and HAART. However, the early increase of naïve CD4 seen in this study is in sharp contrast with HAART where naïve CD4 elevation is a late event. More studies are needed to assess whether this finding is a redistribution phenomenon or an early sign of immune reconstitution.
P9 A PRELIMINARY PHARMACOKINETIC AND PHARMACODYNAMIC EVALUATION OF THE HIV PROTEASE INHIBITOR BMS-232632 IN A PROTEASE INHIBITOR-NAÏVE HIV+ POPULATION
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P9
AIDS 2000, Oct 22-26;14(Suppl. 4);S19
E. O’Mara1, P. Piliero2, G. Drusano2, V. Mummaneni1, R. Raymond1, S. Preston2, A. Schuster1 and D. Randall1
Analysis of variance was used to evaluate the change from baseline (day 1) to mono-(day 15) then combination therapy (day 29) in HIV RNA. Linear regression analysis was used to assess the relationship between BMS Cmin values and changes in HIV RNA by day 15 and day 29. Least square means calculated for ΔHIV RNA between baseline and day 15 and day 29 were 1.342 and 1.85 log copies respectively. . . .
P10 THERAPY-DRIVEN VIRAL EVOLUTION IN MULTIDRUG-EXPERIENCED HIV-1-INFECTED PATIENTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P10
AIDS 2000, Oct 22-26;14(Suppl. 4);S19
S. La Seta Catamancio, E. Bulgheroni, P. Citterio, F. Croce, M. Lo Cicero, M. Galli and S. Rusconi
At the end we detected additional mutations: K103K/N and Y181C with the disappearance of mutations at the positions 41 and 184, in the RT gene, while the mutations 164I/V, V82V/I and L90M appeared in the protease. We evidenced a viral evolution in two heavily drug-experienced patients with a stable high viral load. The genotypic and phenotypic pattern of their resistant virus mirrored with the therapeutic regimen used over time. Growth competition experiments are planned in order to assess the extent of relative viral fitness in the presence/absence of different enzyme inhibitor.

P11 THE USE OF MYCOPHENOLIC ACID, AN INOSINE MONOPHOSPHATE DEHYDROGENASE INHIBITOR, AS PART OF SALVAGE THERAPY IN LATE STAGE HIV DISEASE
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P11
AIDS 2000, Oct 22-26;14(Suppl. 4);S20
C.M. Toukas and G.E. Hatzakis
This small cohort of individuals with advanced HIV disease tolerated MA as part of salvage therapy. At 24 weeks a reduction in viral load, decrease in T cell activation and an increase in CD4 cell count was noted although not significant. Clinical trials of IMPDH inhibitors in HIV disease are thus warranted.
P12 VIROLOGICAL EVALUATION OF THE EFFICACY OF THREE COMPLEMENTARY THERAPIES IN HIV-1 INFECTED INDIVIDUALS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P12
AIDS 2000, Oct 22-26;14(Suppl. 4);S20
Louise C. Dann1, Clive Loveday1 and Bob Jacobs2
No group showed a significant decline in plasma viral load (> 0.5 log copies/ml) during therapy, or a CD4 cell increase. All therapies appear to be well tolerated. Positive responses to complementary therapy were not apparent in any of the studies in individuals not taking any other form of antiretroviral therapy. We continue to monitor new complementary therapies for virological and immunological benefits.
P13 TREATMENT OF THE PATIENTS WITH INTOLERANCE TO AZT BY PHOSPHAZID
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P13
AIDS 2000, Oct 22-26;14(Suppl. 4);S20
O. Yurin, A. Kravtchenko, L. Afonina, N. Buruva, E. Voronin and V. Pokrovsky
The replacement of AZT with PhAZT for patients with intolerance for AZT allows them to continue the antiretroviral therapy with success.
P14 TIPRANAVIR (PNU-140690) RETAINS A POTENT ANTIVIRAL IN VITRO ACTIVITY AGAINST HIV-1 ISOLATES DERIVED FROM PI-NAÏVE OR PI-EXPERIENCED PATIENTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P14
AIDS 2000, Oct 22-26;14(Suppl. 4);S20
E. Bulgheroni, S. La Seta Catamancio, P. Citterio, M. Galazzi, F, Croce, M. Galli and S. Rusconi
Mean values of single target IC50 were 0.224 µM for TPV, 0.004 µM for EFV, 0.027 µM for NFV, 0.393 µM for ABC and 0.080 µM for APV in 14aPre infections; 0.268 µM for TPV, 0.006 µM for EFV, 0.277 µM for NFV, 0.910 µM for ABC and 0.111 µM for APV in CF infections. No toxicity appeared at the highest concentrations used for the entire duration of the experiments. Tipranavir demonstrated activity against a WT HIV-1 isolate and an isolate derived from a heavily PI-experienced patient. Further evaluation of this compound will include combination experiments with dual or triple regimens in vitro.
1.2 POST-EXPOSURE PROPHYLAXIS
Abstracts P15 thru P83, Pages S21 TO S40
P15 48 WEEK RESULTS OF THE CNAF3007/ECUREUIL OPEN LABEL STUDY: EFFICACY AND SAFETY OF THE TRIPLE NUCLEOSIDE COMBINATION COMBIVIR/ABACAVIR VERSUS COMBIVIR/NELFINAVIR AS FIRST-LINE ANTIRETROVIRAL THERAPY IN HIV-1 INFECTED ADULTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P15
AIDS 2000, Oct 22-26;14(Suppl. 4);S21
S. Matheron1, F. Brun Vezinet1, C. Katlama2, J.M. Livrozet3, D. Sicard4, H. Gallais5, F. Boue6, C. Thiaux7 and J.P. Mamet7, on behalf on the CNAF3007/Ecureuil study group
The triple nucleoside combination combivir/abacavir is generally well tolerated first line ART in HIV-1 infected adults, with comparable antiviral activity to a protease inhibitor containing regimen at Week 48.
P16 DIVERGENT INDUCTION FOLLOWED BY LONG TERM CONVERGENT ANTIRETROVIRAL THERAPY IN HIV POSITIVE PATIENTS WITH HIGH RISK OF THERAPY FAILURE
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P16
AIDS 2000, Oct 22-26;14(Suppl. 4);S21
Olaf Degen, Jan van Lunzen, Knud Schewe and Hans-Jürgen Stellbrink
A regimen of divergent quadruple-drug induction, followed by convergent quadruple-drug maintenance therapy is highly active and well tolerated in patients at high risk of early failure. Prospective trials are needed to compare this approach with standard regimens.
P17 VIRAL RESPONSE AT WEEK 16 PREDICTS FUTURE TREATMENT SUCCESS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P17
AIDS 2000, Oct 22-26;14(Suppl. 4);S21
H.A. Stirnadel1, C. Craig1, A.M. Hill1 and L.J. Wheat2
In conclusion, the differences in the rate of decay from treatment initiation up to week 4 appeared to be an indicator of long-term treatment response. However, suppression of HIV-1 RNA to < 400 copies/ml by week 16 was the most important predictor of a durable response up to week 48. We, therefore, suggest that monitoring week 16 viral load might encourage continuation, change or intensification of therapy.
P18 HAART AND THE BRAIN
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P18
AIDS 2000, Oct 22-26;14(Suppl. 4);S22
A. Kandanearatchi, G. Trillo-Pazos, D. King, J. Eyeson, A. Vyakarnam, M. Smith, M. Zukerman and I.P. Everall
This data demonstrates that NRTIs can prevent neuronal loss and microglial cell proliferation in this aggregate model infected with HIV. Such protective properties indicate that these agents will be efficacious in the treatment of HIV associated cognitive impairments. Importantly, this model is being used to test which other drugs prevent HIV associated brain damage.
P19 Comparing PI and NNRTI regimens using clinical databases
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P19
AIDS 2000, Oct 22-26;14(Suppl. 4);S22
A.C. Ghani, C.A. Donnelly, A.W. Roddam, W. Henley, R.M. Anderson
Not available
P20 RESPONSE TO LOPINAVIR-BASED MULTIDRUG RESCUE REGIMENS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P20
AIDS 2000, Oct 22-26;14(Suppl. 4);S22
M. Harris, W. Stewart, G. Larsen, P.R. Harrigan and J.S.G. Montaner
In conclusion, exposure to multiple PIs and mutations associated with PI resistance do not preclude a VL response to multidrug rescue regimens including LPV.
P21 SUCCESSFUL SUBSTITUTION OF PROTEASE INHIBITORS WITH EFAVIRENZ IN PATIENTS WITH UNDETECTABLE PLASMA HIV-1 RNA LEVELS: RESULTS OF A PROSPECTIVE, RANDOMIZED, MULTICENTER, OPEN-LABEL STUDY (DMP 266–049)
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P21
AIDS 2000, Oct 22-26;14(Suppl. 4);S22
S. Becker1, A. Rachlis2, J. Gill3, E. DeJesus4, G. Pierone5, L. Kirkland6, S. Koosian7, D. Farina8, D. Labriola8, N. Ruiz8, L. Bessen8, S. Villano8 and the Study 049 Team1
EFV substitution of a PI, in a suppressive PI-containing regimen, successfully maintains full antiretroviral control (plasma HIV-1 RNA levels ≤ 50 copies/ml) and continued increases in CD4 counts up to 24 weeks.
P22 EFFICACY AND SIDE EFFECTS OF EFAVIRENZ: A RETROSPECTIVE CASE REVIEW
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P22
AIDS 2000, Oct 22-26;14(Suppl. 4);S22
A. Cochrane, A. Pithie, D. Kennedy, R. Fox and A. Thomson
In conclusion the efficacy of efavirenz based triple therapy prescribed in the Brownlee centre is comparable to published data, but more patients than expected were unable to tolerate the drug.
P23 EFAVIRENZ DOES NOT ADD SIGNIFICANTLY TO A DEEP SALVAGE ANTIRETROVIRAL THERAPY INCLUDING A NOVEL PROTEASE INHIBITOR, WITH OR WITHOUT A NOVEL NUCLEOSIDE ANALOGUE
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P23
AIDS 2000, Oct 22-26;14(Suppl. 4);S23
R. Manfredi, E. Rizzo, L. Calza and F. Chiodo
The need of salvage antiretroviral strategies is increasingly frequent in HIV-infected patients. A deep rescue therapy including EFZ plus a novel protease inhibitor is not expected to obtain a complete and sustained virologic success, in patients highly experienced with both nucleoside analogues and protease inhibitor-containing HAART, and a concurrent elevated viral load (> 104 copies/ml in our series), probably due to the extensive viral resistance pattern acquired through time. However, the immunological response proved better than the virologic one, as evaluated during a quite prolonged follow-up. The concurrent change of at least one nucleoside analogue may add significantly, especially during the first 6 months of salvage therapy.
P24 NELFINAVIR PLUS EFAVIRENZ IN NAÏVE SUBJECTS WITH HIGH BASELINE VIRAL LOAD AND IN PATIENTS FAILING PIS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P24
AIDS 2000, Oct 22-26;14(Suppl. 4);S23
V. Oller, P. Barreiro, V. Soriano and J. González-Lahoz
In summary, a quadruple combination including NFV plus EFV provides a significant virologic and immunologic benefit in naïve patients with high baseline VL and, to a lesser extent, in patients failing previous PI-containing combinations.
P25 EFAVIRENZ EXPANDED ACCESS PROGRAM: NORTH AMERICAN EXPERIENCE
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P25
AIDS 2000, Oct 22-26;14(Suppl. 4);S23
D.J. Manion, K.Z. Koziak, D.S. Block, W.C. Montgomery, J.L. Joseph and L.J. Bessen
In conclusion, in heavily ARV-experienced patients, EFV was generally well tolerated, with rates of AE-associated discontinuation similar to those observed in clinical trials. Previous treatment with an NNRTI was associated with lesser reductions in plasma HIV RNA levels.
P26 EFAVIRENZ IN END STAGE RENAL DISEASE
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P26
AIDS 2000, Oct 22-26;14(Suppl. 4);S23
K.P. Prime1, E.M.A. Jungmann1, M.R. Pakianathan1 and I. Woolfson2
EFV, AZT and 3TC are not known to be nephrotoxic. The Hb drop, if significant, could be accounted for by AZT myelotoxicity or ESRD. EFV is known to cause disruption of LFTs and has potential to interact with Amlodipine. However, the ALP rise may be due to 2° hyperparathyroidism seen in ESRD. EFV, AZT and 3TC were well tolerated, safe and effective in this HIV positive patient on CAPD despite pre-existing high pill burden and potential for drug interaction. Increase in CD4 count and reduction in VL to below 50 copies/ml was achieved at 12 weeks. Sustainability and long term safety of this regimen are yet to be confirmed.
P27 CLINICAL, IMMUNOLOGICAL AND VIROLOGICAL RESPONSE TO EFAVIRENZ IN COMBINATION WITH OTHER ANTIRETROVIRAL DRUGS AMONG HIV-INFECTED ROMANIAN ADULTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P27
AIDS 2000, Oct 22-26;14(Suppl. 4);S24
S. Erscoiu1, D. Ispas1, S. Florescu1, C. Cotiga2, C. Chirculescu2, D. Duiculescu2, P. Calistru1 and E. Ceauşu1
Clinical progression of the disease was registered only in one patient. EFV in different ART combinations demonstrated durable suppression of the disease and VL with CD4 recovery and maintenance over an extended period.
P28 'MAINTENANCE' HAART WITH SAQUINAVIR HARD GEL, SPONTANEOUSLY REQUESTED BY PATIENTS DECLINING THE PROSECUTION OF A SUCCESSFUL HAART INCLUDING A POTENT PROTEASE INHIBITOR
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P28
AIDS 2000, Oct 22-26;14(Suppl. 4);S24
R. Manfredi and F. Chiodo
Although the continuation of an anti-HIV regimen of maximal potency is presently recommended to patients favorably treated with an HAART association containing a potent protease inhibitor, ‘maintenance’ regimens carried out after a heavy induction HAART, and including drugs with an expected lower potency but better tolerability and compliance profiles, deserve some investigation. In fact, a few literature studies dealing with failure of some ‘maintenance’ strategies, were severely limited by short induction periods, or drug associations which were not expected to sustain viral suppression, while a triple combination containing SQV hard gel has not been assessed to date in patients who had a favorable prior response to IDV-, RTV, or NFV-containing HAART.
P29 THERAPEUTIC EFFECTS OF ANTIRETROVIRAL THERAPY REGIMENS ON THE CENTRAL NERVOUS SYSTEM: IMPACT OF DIFFERENT FORMS OF PRETREATMENT
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P29
AIDS 2000, Oct 22-26;14(Suppl. 4);S24
G. Arendt, H.J. v. Giesen, A. Theisen1 and H. Hefter
Despite different forms of pretreatment, HAART has a significant therapeutic effect on the CNS for at least 6 months.
P30 THERAPEUTIC EFFECTS OF ANTIRETROVIRAL THERAPY REGIMENS ON THE CENTRAL NERVOUS SYSTEM: VALUE OF DIFFERENT THERAPY REGIMENS IN THERAPY-NAÏVE PATIENTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P30
AIDS 2000, Oct 22-26;14(Suppl. 4);S25
H.J. v. Giesen, A. Theisen1, H. Hefter and G. Arendt
In therapy-naïve patients combinations including two nucleoside analogues with or without a protease inhibitor showed a comparable therapeutic effect on the CNS.
P31 EFFECTIVE LONG-TERM REDUCTION OF CEREBROSPINAL FLUID VIRAL LOAD BY HAART IN ANTIRETROVIRAL NAÏVE HIV-1 INFECTED INDIVIDUALS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P31
AIDS 2000, Oct 22-26;14(Suppl. 4);S25
M. Gisslén, L. Hagberg and B. Svennerholm
HAART effectively reduces CSF viral load for at least 2–4 years in antiretroviral naïve HIV-1 infected individuals without neurological symptoms.
P32A INDINAVIR PLUS RITONAVIR AS SALVAGE THERAPY IN HIV INFECTION
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P32A
AIDS 2000, Oct 22-26;14(Suppl. 4);S25
I. Santos, P. González-Ruano and J. Sanz
1.-We observed a significant benefit in the viral load decrease, and remained stable over follow-up. 2.-The benefit was more important in the patients that had never taken RTV and/or IDV, but had experienced protease inhibitors. 3.-IDV plus RTV in combination at the mentioned doses may represent a good therapeutic option in patients with multiple failures to HAART.
P32B ADVERSE EVENTS OF INDINAVIR PLUS RITONAVIR AS SALVAGE THERAPY IN HIV INFECTION
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P32B
AIDS 2000, Oct 22-26;14(Suppl. 4);S25
I. Santos, P. González-Ruano and J. Sanz
We observed a high incidence of adverse events and a high percent of withdrawal of the medication study, but the efficacy in some appropriated cases can make this combination very useful.
P33 PERFORMANCE OF RITONAVIR PLUS INDINAVIR AS PART OF SALVAGE REGIMENS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P33
AIDS 2000, Oct 22-26;14(Suppl. 4);S26
P. Barreiro, V. Oller, V. Soriano and J. González-Lahoz
In conclusion, the combination of RTV+IDV constitutes a potent option for salvage interventions. These benefits are counterbalanced with a high incidence of adverse effects, which could be explained by the overlapping toxicity profile of RTV and IDV, and the poor tolerance the RTV liquid formulation.
P34 A DUAL PROTEASE INHIBITOR (PI)-BASED REGIMEN INCLUDING INDINAVIR (IDV) 800 MG TWICE DAILY (BID) PLUS RITONAVIR (RTV) 200 MG BID SHOWS EARLY PROMISE IN LOWERING SERUM HIV RNA LEVELS IN HIV-INFECTED PERSONS WITH EXTENSIVE PROTEASE (PR) MUTATIONS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P34
AIDS 2000, Oct 22-26;14(Suppl. 4);S26
R.D. MacArthur, J.M. Kosmyna and L.R. Crane
The 0.7 log10 copies/ml (5-fold) drop in serum HIV RNA level and 20% increase in CD4+ lymphocyte cell count at 2 months, if sustained, suggest that many HIV-infected persons previously treated with PIs may benefit from this IDV + RTV-based AR regimen.
P35 IDV/RTV 800/200 MG BID AS SALVAGE THERAPY FOR PI FAILURES: MERCK 088
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P35
AIDS 2000, Oct 22-26;14(Suppl. 4);S26
M. Robertson1, R. Campo2, D. Butcher3, D. Johnson4, R. Larsen4, J. Eron4, P. Piliero6, D. Marino1, M. Nessley1, R. Leavitt1
In this study, the majority of patients responded to therapy with IDV 800 mg + RTV 200 mg. This IDV/RTV regimen may have a role as salvage therapy in patients who have failed a PI containing regimen, including patients who have failed IDV.
P36 DOUBLE PI STUDY: INDINAVIR Q8H + D4T/3TC BID VERSUS INDINAVIR/NELFINAVIR BID + D4T/3TC BID (MERCK PROTOCOL 079)
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P36
AIDS 2000, Oct 22-26;14(Suppl. 4);S26
J. Nadler1, W.J. Fessel2, L. Kirkland3, S. Maloney4, N. Bohidar4, H.Wilson4, E. Edelstein4 and J. Schranz4
Preliminary 24-week results suggest both bid/4 DR and q8h/3 DR exhibit potent antiviral activity. Updated information including response by baseline stratum will be presented.
P37 DIRECT STUDY: A MULTICENTER, OPEN LABEL, 24-WEEK PILOT STUDY WITH A 24-WEEK EXTENSION TO EVALUATE THE SAFETY, TOLERABILITY AND EFFICACY OF INDINAVIR/RITONAVIR (800/100) BID IN COMBINATION WITH D4T PLUS 3TC IN HIV-INFECTED INDIVIDUALS (MERCK PROTOCOL 094)
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P37
AIDS 2000, Oct 22-26;14(Suppl. 4);S27
M. Fischl1, M. Watkins2, B. Young3, J. Fessel4, N. Bohidar5, H. Wilson5, K. Guckert5, J. Schranz5
Overall the regimen was generally well tolerated. Five of 50 patients (10%) have developed nephrolithiasis. At the time of this summary 42 patients either completed or are continuing. Two patients have 2) pneumonia, dehydration and acute renal failure. Preliminary data demonstrated that IDV-RTV (800/ 100) bid + d4T/3TC was generally well-tolerated with potent antiretroviral activity. Additional data will be presented.
P38 BID FIRST-LINE RITONAVIR/INDINAVIR 24 WEEK RESULTS: GERMAN MULTICENTER STUDY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P38
AIDS 2000, Oct 22-26;14(Suppl. 4);S27
A. Wickesberg1, P. Gute2, L. Locher2, B. Salzberger3, A. Wöhrmann3, A. Adam4, L. Weitner4, F. Bergmann5, K. Schliefer1 and J.K. Rockstroh1 for the German Ritonavir/Indinavir Study Group
Our preliminary data suggest that even in the presence of high median baseline HIV-RNA levels the protease inhibitor combination RTV/IDV (2 × 100/2 × 800 mg) plus double/triple nucleoside therapy appears effective and safe in therapy naïve patients based on short-term treatment up to week 24. Nephrolithiasis occurred in 15% and therefore patients need extra hydration. The study is ongoing and further clinical and laboratory data will be presented.
P39 HIGH EFFICACY OF INITIAL 3-CLASS, 4-DRUG ANTIRETROVIRAL THERAPY (ART) IN THERAPY-NAÏVE HIV PATIENTS WITH HIGH VIRAL LOAD
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P39
AIDS 2000, Oct 22-26;14(Suppl. 4);S27
F. Meienberg1, H.C. Bucher1, P. Taffé2, M. Rickenbach2 and M. Battegay1 for the Swiss HIV Cohort Study (SHCS)
In patients with very high viral load clinicians may consider ART with an initial 3-class, 4-drug regimen due to high efficacy in terms of viral suppression and CD4 cell increase, although results from controlled studies are pending.
P40A EFFICACY OF AMPRENAVIR (APV) 600 MG PLUS LOW-DOSE RITONAVIR (RTV) IN CLINICAL PRACTICE
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P40A
AIDS 2000, Oct 22-26;14(Suppl. 4);S28
A.D. Luber1,2, R. Stryker 1,2, J. Burdick 1,2, M.M. Berrey3, O. Naderer3 and A. Scarsella1
These data suggest that combination ART regimens of APV 600 mg/low dose RTV appears promising for the treatment of antiretroviral experienced HIV-infected individuals. Prospective, multicenter trials evaluating APV600/RTV100 bid are currently underway.
P40B SUSTAINED VIRAL SUPPRESSION WITH AMPRENAVIR PLUS RITONAVIR IN COMBINATION WITH ABACAVIR/ZIDOVUDINE/LAMIVUDINE IN HEAVILY PRETREATED PATIENTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P40B
AIDS 2000, Oct 22-26;14(Suppl. 4);S28
P. Gute1, L. Locher1, A. Carlebach2, T. Lutz2, S. Staszewski2 and V. Miller2
This preliminary study analysis indicates that salvage treatment based on amprenavir/ritonavir plus abacavir appears to be well tolerated, and results in a favourable and sustainable virologic response in patients with extensive prior antiretroviral exposure. The role of viral drug susceptibility will be investigated.
P41 RITONAVIR (RTV)/AMPRENAVIR (APV) COMBINATION THERAPY IN HIV INFECTED PATIENTS WHO FAILED SEVERAL PROTEASE INHIBITOR CONTAINING REGIMEN
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P41
AIDS 2000, Oct 22-26;14(Suppl. 4);S28
C. Katlama, L. Schneider, R. Agher, C. Delaugerre, V. Calvez, M. Legrand and R. Tubiana
This pilot retrospective study shows that in patients with multiple failures to PI containing regimen, RTV/AMP appears as a potent antiviral option with a median 1.6 log10 reduction in VL after 12 weeks.
P42 DIFFERENCES IN VIRAL LOAD OUTCOMES AT 90, 180 AND 170 DAYS IN PROTEASE INHIBITOR (PI)-NAÏVE PATIENTS TREATED WITH DUAL VERSUS SINGLE THERAPY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P42
AIDS 2000, Oct 22-26;14(Suppl. 4);S29
D. Butcher1, S. Mayer2, C. de Guzman3, E. Hamel3 and D. Lapins3
The dual PI cohort experienced significantly greater log VL decreases at 90, 180 and 270 days than the single PI cohort, regardless of therapy switching during this time period. These results suggest that patients with no prior PI experience can benefit from first-line dual PI therapy. Additional retrospective data and prospective controlled clinical trials are needed to strengthen these conclusions.
P43 ABT-378/RITONAVIR (ABT-378/R) AND EFAVIRENZ: ONE YEAR SAFETY/EFFICACY EVALUATION IN MULTIPLE PI EXPERIENCED PATIENTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P43
AIDS 2000, Oct 22-26;14(Suppl. 4);S29
J. Rockstroh1, S. Brun12, J. Sylte12, Y. Xu12, N. Clumeck2, A. Lazzarini3, P.M. Girard4, S. Becker5, A. Telenti6, F. Bergmann7, S. Danner8, D. Ho9, R. Tubiana10, G. Carosi1, R. Bertz12, A. Hsu12, D.J. Kempf12 and E. Sun12 for the M98–957 study
The safety and efficacy of ABT-378/r and efavirenz plus NRTIs is encouraging in patients with extensive PI experience.
P44 EVALUATION OF ABT-378/RITONAVIR (ABT-378/R) BASED SALVAGE REGIMES IN A COHORT OF HIV-INFECTED PATIENTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P44
AIDS 2000, Oct 22-26;14(Suppl. 4);S29
J.N. Day, A.J. Uriel, R. Daintith, E.M. Dunbar, D.W. Denning, E.G.L. Wilkins and A. Bonington
Our data suggests that ABT-378/r is well tolerated with 85% of patients achieving a reduction in viral load of greater than 1.0 log by 4 weeks. Phenotypic evidence of resistance to more than one PI suggests a less favourable response to ABT-378/r.
P45 SAFETY AND EFFICACY OF ABT 378/R IN THE GERMAN EXPANDED ACCESS PROGRAM (EAP)
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P45
AIDS 2000, Oct 22-26;14(Suppl. 4);S29
E. Voigt, J.C. Wasmuth, D. Braitinger, B. Kupfer1, R. Kaiser2, J.K. Rockstroh
ABT 378/r is a highly active antiretroviral drug even in heavily pretreated patients with high level resistance. The overall rate of adverse events is low. Our preliminary data shows no evidence of rapid developing resistances in patients virologically failing ABT 378/r. However further data is required to allow reliable conclusions on resistance under ABT 378/r.
P46 ABT-378/RITONAVIR (ABT-378/R) IN ANTIRETROVIRAL NAÏVE HIV+ PATIENTS: FOLLOW-UP BEYOND 2 YEARS AND VIRAL LOAD SUPPRESSION BELOW 3 COPIES/ML
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P46
AIDS 2000, Oct 22-26;14(Suppl. 4);S30
R. Stryker1, S. Brun13, M. King13, T. Marsh13, R. Murphy2, C. Hicks3, J. Eron4, J. Thommes1, R. Gulick5, M. Glesby5, M. Thompson6, C. White7, C. Benson8, M. Albrecht9, H. Kessler10, K. Real12, A. Japour12, L. Perrin11 and E. Sun12 for the M97.720 Study Group
ABT-378/r + d4T + 3TC exhibits durable antiviral activity beyond two years of treatment in treatment-naïve HIV-infected patients.
P47 RITONAVIR 400 MG BID COMPARED WITH RITONAVIR 600 MG BID IN PROTEASE INHIBITOR-NAÏVE SUBJECTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P47
AIDS 2000, Oct 22-26;14(Suppl. 4);S30
M. Sension1, G. Beall2, D. Parenti3, P. Keiser4, E. Yakim5, K. Selness6 and M.F. Giordano7
When combined with d4T and 3TC over a 48-week pilot study, RTV 400 mg bid did not statistically significantly differ from RTV 600 mg bid in its antiviral activity. Fewer patients discontinued the study for adverse events in the RTV 400 mg bid arm. An adequately powered, controlled study would be needed to determine the equivalence of these two regimens.
P48 DUAL PI-CONTAINING REGIMEN WITH NELFINAVIR (NFV)/SAQUINAVIR (SQV) AT A SINGLE HIV OUTPATIENT CLINIC
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P48
AIDS 2000, Oct 22-26;14(Suppl. 4);S30
M. Vazquez, H. Perez, C. Zala and P. Cahn
Overall, dual PI-based therapy with NFV/SQV was well tolerated and effective in both naïve and PI experienced patients.
P49 EFFICACY OF AMPRENAVIR, RITONAVIR AND EFAVIRENZ IN TREATMENT EXPERIENCED HIV-INFECTED PATIENTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P49
AIDS 2000, Oct 22-26;14(Suppl. 4);S31
K. Römer, B. Salzberger, C. Franzen, D. Waldschmidt and G. Fätkenheuer
The combination of amprenavir, ritonavir and efavirenz is well tolerated and shows good antiretroviral activity in a substantial proportion of patients with virological failure to their previous regimens.
P50 SWITCHING FROM PROTEASE INHIBITORS (PI) TO EFAVIRENZ (EFV) IN PATIENTS WITH UNDETECTABLE VIRAL LOAD: IMPACT ON CONSECUTIVE CD4+ CELL COUNT
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P50
AIDS 2000, Oct 22-26;14(Suppl. 4);S31
E. Lauenroth-Mai1, J. Bogner2 and B. Salzberger3
Due to the nonrandomized nature of this retrospective analysis, the results of significance analysis are rather descriptive than confirmatory. Still they indicate that the substitution from PI to EFV in subjects with sustained undetectable plasma HIV RNA levels may provide an immunologic benefit. This observation needs to be confirmed by further prospective studies.
P51 SWITCHING PI TO NNRTI: EVALUATION OF THE EFFICIENCY ON UNDETECTABLE PATIENTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P51
AIDS 2000, Oct 22-26;14(Suppl. 4);S31
F. Chauvelot, D. Blancher, M. Walter, J. Gaillat and J.P. Bru
The results of this therapeutic alternative are interesting. Nevertheless, they must be reassessed and confirmed by a wider and longer study.
P52 IMMUNE RESPONSE TO A FIRST HAART REGIMEN: NNRTI VERSUS PI-BASED COMBINATIONS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P52
AIDS 2000, Oct 22-26;14(Suppl. 4);S31
P. Barreiro, V. Soriano, E. Casas and J. González-Lahoz
In conclusion, an abrupt increase in CD4 cells occurs shortly after HAART is introduced. This response mainly reflects CD4 cell redistribution. Late increases in CD4 counts, mostly due to the naïve subset, seem to be higher in subjects experiencing a good virological response under PI-containing regimens than among those being under NNRTIs.
P43 STEPWISE TREATMENT DISCONTINUATION IN PATIENTS SHOWING GOOD VIROLOGICAL CONTROL ON TREATMENT
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P53
AIDS 2000, Oct 22-26;14(Suppl. 4);S31
P. Barreiro, C. de Mendoza, V. Soriano and J. González-Lahoz
In conclusion, HU–ddI might represent an optional therapy after a sustained success on HAART. The presence of persistent low-grade virus replication on HU–ddI could elicit CD4–CD8 lymphocyte responses which in the long-term might allow to control HIV replication without any antiviral treatment.
P54 EFFICACY OF NELFINAVIR (NFV) SALVAGE WITH A NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NNRTI) IN HEAVILY PRE-TREATED PATIENTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P54
AIDS 2000, Oct 22-26;14(Suppl. 4);S32
J.G. Baril, P. Junod, F. Laplante, D. Tessier, P. Cote, S. Dufresne and Y. Parent
Therefore, we conclude that NFV in combination with DLV or EFV offers effective salvage in heavily pre-treated patients. Although significance could not be determined due to small sample size, a lower mean duration of HIV/AIDS or a lower mean number of prior HAART regimens appeared to be associated with positive response.
P55 EFFICACY AND TOLERABILITY OF TWICE DAILY ZALCITABINE
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P55
AIDS 2000, Oct 22-26;14(Suppl. 4);S32
F. Antunes1 and M. Doroana2 on behalf of the HIVBID Study Group
In conclusion, this interim analysis suggest that zalcitabine is effective and well tolerated when administered twice daily, with similar antiretroviral activity to that of the more commonly used regimen of 3TC/ZDV plus a PI for all parameters evaluated.
P56 IMPACT OF ABACAVIR ON AN HIV OUTPATIENTS' CLINIC INTENSIFICATION OF DUAL NUCLEOSIDE THERAPY IN LONG-TERM TREATED PATIENTS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P56
AIDS 2000, Oct 22-26;14(Suppl. 4);S32
A. Capetti, C. Magni, P. Bonfanti and M.C. Vivirito
The numbers are still small and this is an historical population that is unlikely to grow very much in size (at present dual nucleoside therapy is proposed only to psychiatric patients who are poorly compliant and absolutely need antiretroviral therapy). However our data show the clear potency of abacavir being added as the only new drug in a setting where previous nucleoside exposure should have reduced viral sensitivity to the drug. Unfortunately at the time the study was started baseline resistance testing was not taken into account.
P57 SHOULD THE M184V MUTATION IN RT BE MAINTAINED AS A COMPONENT OF HIV TREATMENT STRATEGIES?
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P57
AIDS 2000, Oct 22-26;14(Suppl. 4);S33
Mark A. Wainberg and Matthias Gotte
These data provide support for the notion that the effectiveness of ABC and ZDV may be sustained, at least temporarily, in the presence of the M184V mutation. However the notion that M184V can confer benefit remains hypothetical and clinical trials are required to validated disprove this hypothesis.
P58 OPEN, MULTICENTRIC RANDOMIZED STUDY TO EVALUATE EFFICACY AND SECURITY OF NELFINAVIR 750 MG TID VERSUS 1250 MG BID, ASSOCIATED WITH 3TC AND D4T, IN HIV INFECTED PATIENTS: CONCOMITANT EVALUATION OF HIV GENOTYPING AND COMPLIANCE TO TREATMENT. ESPARTA 001 –'PAULISTA' STUDY FOR ANTIRETROVIRAL THERAPEUTIC REGIMEN EVALUATION
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P58
AIDS 2000, Oct 22-26;14(Suppl. 4);S33
Marilia S. Oliveira, Olavo H.M. Leite, Jane I. Varandas, David E. Uip and ESPARTA Group
We concluded that NFV 750 mg tid and 1250 mg bid, associated with 3TC and d4T, have similar patterns of efficacy in 12 weeks of treatment.
P59 ABACAVIR (ABC) BASED TRIPLE NUCLEOSIDE ANALOGUES (NRTIS) VERSUS PROTEASE INHIBITOR (PI) CONTAINING REGIMENS IN ANTIRETROVIRAL NAÏVE PATIENTS WITH A CD4 COUNT OF LESS THAN 100 AND/OR AIDS: OBSERVATIONAL DATA FROM THE FRANKFURT COHORT
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P59
AIDS 2000, Oct 22-26;14(Suppl. 4);S33
C. Rottmann1, V. Miller1, A. Haberl1, A. Muller1, H. Rabenau2, S. Staszewski1
In this observational study of treatment response with heavily immunocompromised patients, no differences regarding virological, immunological and clinical treatment response were detected between the two groups. However further studies with larger patient cohorts and longer follow-up period are required.
P60 DOES THE CHOICE BETWEEN NNRTI OR PI BASED INITIAL HAART PREDICT VIROLOGICAL SUPPRESSION AT 24 WEEKS IN A CLINICAL SETTING?
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P60
AIDS 2000, Oct 22-26;14(Suppl. 4);S33
G.V. Matthews, S. Mandalia, M. Nelson, M. Bower and B.G. Gazzard
This is the first cohort analysis to support clinical trial data on the potential superiority of an NNRTI combination in initial HAART regimens and may reflect the greater tolerability of these combinations.
P61 PROTEASE INHIBITOR (PI) SPARING REGIMENS IN PATIENTS WITH ADVANCED HIV DISEASE (CD4 < 200/MM3) AND NAÏVE FOR ANTIRETROVIRAL THERAPY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P61
AIDS 2000, Oct 22-26;14(Suppl. 4);S34
D. Konopnicki, H. Ait Mohand, M. Tpilo-Zavala, E. Chiesa, P. Bossi, M.A. Valantin, C. Delaugerre, V. Calvez, F. Bricaire and C. Katlama
These preliminary results suggest that first line PI sparing regimens using NRTIs and NNRTI combination are highly effective, safe and appropriate to patients with advanced HIV disease regarding to compliance and heavy concomitant therapies.
P62 MAINTENANCE OF VIROLOGICAL SUPPRESSION IN PATIENTS SWITCHED FROM INDINAVIR (IDV) TO NELFINAVIR (NFV)
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P62
AIDS 2000, Oct 22-26;14(Suppl. 4);S34
E. Lefebvre1 and S. Shafran2
Most commonly cited reasons for switch to NFV were: physician preference (23.2%), GI upset (19.6%), adherence issues (19.6%) and urolithiasis (14.3%). To date 30 patients remain on the same NFV regimen; 13 changed to a different regimen and four stopped therapy altogether. Patients maintained further virological suppression (on average 55.7 weeks) after switching to NFV, which provided a total protease inhibitor treatment duration of approximately 110 weeks. Therefore, in patients intolerant of IDV, who are controlled virologically, switching to NFV is a reasonable option.
P63 PREDICTORS OF VIROLOGICAL FAILURE AMONG PATIENTS STARTING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P63
AIDS 2000, Oct 22-26;14(Suppl. 4);S34
E. Florence, C. Dreezen, P. Desmet, E. Smets, A. De Roo, R. Colebunders
Risk factors for virological failure were at baseline, a younger age, a longer duration of seropositivity, a high viral load, a low CD4 count and a low BMI.
P64 AN ANALYTIC REVIEW OF RANDOMIZED, CONTROLLED TRIALS OF SELECTED HAART REGIMENS
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P64
AIDS 2000, Oct 22-26;14(Suppl. 4);S35
C. Renz, P. Foley, T. Ashraf, E. Sun, and M. Luo
This review study suggests that efficacy differences exist among HAART regimens, and tolerability of agents may present a significant clinical problem. A lack of uniform statistical reporting methods can bias comparisons of published results.
P65 VIROLOGICAL SUPPRESSION IN PATIENTS STARTING A SECOND-LINE HAART REGIMEN AFTER STOPPING THEIR FIRST HAART REGIMEN
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P65
AIDS 2000, Oct 22-26;14(Suppl. 4);S35
A. De Luca1, A. Cozzi Lepri2, A. d’ Arminio Monforte1, A.N. Phillips2, F. Alberici1, M. Vigevani1, A. Sinicco1, V. Colangeli1, F. Menichetti1, F. Ghinelli1 and M. Moroni1
Although larger numbers of individuals must be studied before firm conclusions can be drawn, these findings provide insights into the factors affecting response to second HAART regimens in patients who previously received only HAART.
P66 EFFICACY AND TOLERABILITY OF HYDROXYUREA CONTAINING SALVAGE ANTIRETROVIRAL REGIMENS IN THE MANAGEMENT OF HIV INFECTION
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P66
AIDS 2000, Oct 22-26;14(Suppl. 4);S35
P. Harrington, S. Clarke, M. Ryan, C. Bergin and F. Mulcahy
Preliminary data suggest that HU containing salvage regimens are efficacious, consistent with expectations for a cohort of heavily pretreated patients with advanced HIV disease on complicated treatment schedules. HU-containing regimens were associated with significant treatment related morbidity. HU therapy should be used with extreme caution in these patients and the importance of close surveillance cannot be underestimated. Early evidence of haematological toxicity warrants prompt dose reduction or treatment interruption to avert serious drug induced toxicity and consequent morbidity.
P67 A RANDOMIZED, CONTROLLED CLINICAL TRIAL (RACING-TRIAL) COMPARING TWO TREATMENT STRATEGIES
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P67
AIDS 2000, Oct 22-26;14(Suppl. 4);S35
K. Arasteh1, A. Baumgarten1, A. Masuhr1, V. Simon1, T. Zwingers2, A. Moll3, E. Lauenroth-Mai3, C. Moecklinghoff4, M. Kurowski1, M. L’ Age1
VL and CD4 T-lymphocyte count showed no statistically significant difference in the ZDV, ddC, SQV versus the ZDV, 3TC, NFV group, until week 80. Early treatment failures are highly predictable at baseline by the presence of mutations in the RT-gene and SQV drug levels. Late failures appear to depend on low drug levels during therapy, pre-existing mutations, and newly developed mutations during treatment and other known risk factors such as high HIV-RNA at baseline. The mutation pattern between the two arms of patients who had failed (VL > 1000 c/ml) treatment regimens between week 52 and 104 are incongruent.
P68A DRUG HOLIDAYS (DH) IN HIV+ PATIENTS: CLINICAL ISSUES
Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. P68A
AIDS 2000, Oct 22-26;14(Suppl. 4);S36