Response by gender of HIV-1-infected subjects treated with abacavir/lamivudine plus atazanavir, with or without ritonavir, for 144 weeks

Abstract

Purpose

The 144-week results of the open-label, multicenter Atazanavir/Ritonavir Induction with Epzicom Study (ARIES) were stratified by gender to compare treatment responses.

Methods

A total of 369 HIV-infected, antiretroviral-naïve subjects receiving once-daily abacavir/lamivudine + atazanavir/ritonavir (ATV/r) whose HIV-1 RNA was <50 copies/mL by week 30 were randomized 1:1 at week 36 to maintain or discontinue ritonavir for 108 subsequent weeks. Between- and within-treatment gender-related efficacy and safety differences were analyzed.

Results

Subjects were 85% male; 64% white; and had a mean age of 39 years, baseline median HIV-1 RNA of 114,815 copies/mL, and median CD4+ cell count of 198 cells/mm³. Gender (ATV [n=189]: 29 females/160 males; ATV/r [n=180]: 25 females/155 males) and most other demographics were similar between groups; more females than males were black (65% vs 25%) and fewer females had baseline HIV-1 RNA ≥100,000 copies/mL (41% vs 58%). At week 144, no significant differences between genders were observed in proportion maintaining HIV-1 RNA <50 copies/mL (ATV, 79% vs 77%; ATV/r, 60% vs 75%) or <400 copies/mL (ATV, 83% vs 84%; ATV/r, 68% vs 82%) (intent-to-treat-exposed: time to loss of virologic response analysis); median CD4+ change from baseline (ATV, +365 vs +300 cells/mm³; ATV/r, +344 vs +301 cells/mm³); proportion with treatment-related grade 2–4 adverse events (baseline to week 144: ATV, 41% vs 31%; ATV/r, 36% vs 43%; weeks 36 to 144: ATV, 14% vs 13%; ATV/r, 24% vs 23%); or proportion developing fasting lipid changes. Female and male virologic failure rates (ATV, 0 vs 5; ATV/r, 2 vs 4) and proportions completing the study were similar during the extension phase. Primary withdrawal reasons were loss to follow-up and pregnancy for females and loss to follow-up and other for males.

Conclusion

Over 144 weeks, no significant gender differences were observed in efficacy, safety, or fasting lipid changes with abacavir/lamivudine +ATV or abacavir/lamivudine +ATV/r.

Keywords:

• ARIES
• HIV-infected
• gender
• virologic efficacy

Supplementary material

Table S1 List of institutional review boards/independent ethics committee at each study site that approved the protocol

Acknowledgments

We wish to thank the subjects, study coordinators, and investigators who participated in this study and made this analysis possible. ARIES US investigators included B Akil, J Applebaum, N Bellos, D Berger, I Brar, C Brinson, F Carpio-Cedraro, P Cook, M Cuenca, E DeJesus, R Dretler, J Duggan, R Elion, T File, J Gathe, E Godofsky, R Greenberg, R Hao, K Henry, AM Khalsa, J Kort, P Kumar, P Lackey, A LaMarca, C Lucasti, C McDonald, P McLeroth, I Melendez-Rivera, A Mestre, J Morales-Ramirez, R Nahass, C Newman, W O’Brien, P O’Keefe, E Oldfield, H Olivet, T Overton, D Pearce, M Ramgopal, B Rashbaum, F Rhame, G Richmond, J Rodriguez, P Salvato, A Sanchez, J Sarria, L Santiago, K Sathasivam, P Sax, S Schneider, R Scott, A Scribner, G Sepulveda-Arzola, G Simon, D Siraj, J Slim, L Sloan, C Small, K Squires, K Tashima, P Tebas, M Thompson, J Torres, V Trivedi, T Vanig, D Ward, W Weinberg, M Weinert, and B Young. ARIES Canadian Investigators included JG Baril, D Murphy, M Potter, A Rachlis, G Smith, and S Walmsley. Contributors from GlaxoSmithKline included E Blackmon, N Figliola, V Garay, S LaBelle, D Margolis, D Percival, D Raimonde, M Schultz, B Wine, and all the GSK monitors. Bristol-Myers Squibb generously donated study medication.

Funding for this work was provided by ViiV Health-care. The sponsor developed the study design with input from prospective investigators. All listed authors meet the criteria for authorship set forth by the International Committee of Medical Journal Editors. The authors wish to acknowledge the following individual for editorial assistance during the development of this manuscript: Meredith MacPherson.

Author contributions

Substantial contributions to study conception and design were made by KES, BY, LLR, HHZ, and MSS. Substantial contributions to the analysis and interpretation of the data were made by HHZ, KES, LLR, BY, SLW, GEP, and MSS. Substantial contributions to acquisition of patient clinical study data were made by KES, BY, LS, RHD, and SLW. All authors had full access to the data and vouch for the accuracy and completeness of the data and analyses. The manuscript was written and approved by all of the authors, each of whom contributed to the drafts and revisions.

Disclosure

KES has received consultancy fees and/or research funding from Abbott, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Koronis, Merck, Pfizer, Schering-Plough, Tibotec, and Tobira. BY has received consultancy fees, speaking honoraria, and/or research funding from Gilead Sciences, GlaxoSmithKline, Merck, Monogram Biosciences, Pfizer, and ViiV Healthcare. LS has received consultancy fees, speaking honoraria, and/or research funding from Gilead Sciences, GlaxoSmith-Kline, Janssen, Merck, Pfizer, and ViiV Healthcare. RHD is employed by ID Specialists of Atlanta, GA, USA. SLW is employed by University Health Network, Toronto, ON, Canada and has served on advisory boards and spoken at CME events for AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck, and ViiV Healthcare. HHZ is employed by GlaxoSmithKline. LLR, GEP, and MSS are employed by ViiV Healthcare. The authors report no other conflicts of interest in this work.