BACKGROUND: Individual randomized trials of first-line antiretroviral treatment do not consistently show an association between higher baseline HIV-1 RNA and lower efficacy. METHODS: A MEDLINE search identified 21 HIV clinical trials with published analyses of antiretroviral efficacy by baseline HIV-1 RNA, using a standardized efficacy endpoint of HIV-1 RNA suppression <50 copies/mL at week 48. RESULTS: Among 21 clinical trials identified, eight evaluated only nonnucleoside reverse transcriptase inhibitor (NNRTI)-based combinations, eight evaluated only protease inhibitor-based regimens and five compared different treatment classes. Ten of the trials included tenofovir (TDF)/emtricitabine (FTC) as only nucleoside reverse transcriptase inhibitor (NRTI) backbone, in addition but not restricted to abacavir (ABC)/lamivudine (3TC) (n = 7), zidovudine (ZDV)/3TC (n = 4) and stavudine (d4T)/3TC (n = 1). Across trials, the mean percentage of patients achieving HIV-1 RNA < 50 copies/mL at week 48 was 81.5% (5322 of 6814) for patients with baseline HIV-1 RNA < 100 000, vs. 72.6% (3949 of 5556) for patients with HIV-1 RNA > 100 000 copies/mL. In the meta-analysis, the absolute difference in efficacy between low and high HIV-1 RNA subgroups was 7.4% [95% confidence interval (CI) 5.9-8.9%; P < 0.001]. This difference was consistent in trials of NNRTI-based treatments (difference = 6.9%; 95% CI 4.3-9.6%), protease inhibitor-based treatments (difference = 8.4%; 95% CI 6.0-10.8%) and integrase or chemokine (C-C motif) receptor 5 (CCR5)-based treatments (difference = 6.0%; 95% CI 2.1-9.9%) and for trials using TDF/FTC (difference = 8.4%; 95% CI 6.0-10.8%); there was no evidence for heterogeneity of this difference between trials (Cochran's Q test; not significant). CONCLUSIONS: In this meta-analysis of 21 first-line clinical trials, rates of HIV-1 RNA suppression at week 48 were significantly lower for patients w ith baseline HIV-1 RNA > 100 000 copies/mL (P < 0.001). This difference in efficacy was consistent across trials of different treatment classes and NRTI backbones.
BACKGROUND: Individual randomized trials of first-line antiretroviral treatment do not consistently show an association between higher baseline HIV-1 RNA and lower efficacy. METHODS: A MEDLINE search identified 21 HIV clinical trials with published analyses of antiretroviral efficacy by baseline HIV-1 RNA, using a standardized efficacy endpoint of HIV-1 RNA suppression <50 copies/mL at week 48. RESULTS: Among 21 clinical trials identified, eight evaluated only nonnucleoside reverse transcriptase inhibitor (NNRTI)-based combinations, eight evaluated only protease inhibitor-based regimens and five compared different treatment classes. Ten of the trials included tenofovir (TDF)/emtricitabine (FTC) as only nucleoside reverse transcriptase inhibitor (NRTI) backbone, in addition but not restricted to abacavir (ABC)/lamivudine (3TC) (n = 7), zidovudine (ZDV)/3TC (n = 4) and stavudine (d4T)/3TC (n = 1). Across trials, the mean percentage of patients achieving HIV-1 RNA < 50 copies/mL at week 48 was 81.5% (5322 of 6814) for patients with baseline HIV-1 RNA < 100 000, vs. 72.6% (3949 of 5556) for patients with HIV-1 RNA > 100 000 copies/mL. In the meta-analysis, the absolute difference in efficacy between low and high HIV-1 RNA subgroups was 7.4% [95% confidence interval (CI) 5.9-8.9%; P < 0.001]. This difference was consistent in trials of NNRTI-based treatments (difference = 6.9%; 95% CI 4.3-9.6%), protease inhibitor-based treatments (difference = 8.4%; 95% CI 6.0-10.8%) and integrase or chemokine (C-C motif) receptor 5 (CCR5)-based treatments (difference = 6.0%; 95% CI 2.1-9.9%) and for trials using TDF/FTC (difference = 8.4%; 95% CI 6.0-10.8%); there was no evidence for heterogeneity of this difference between trials (Cochran's Q test; not significant). CONCLUSIONS: In this meta-analysis of 21 first-line clinical trials, rates of HIV-1 RNA suppression at week 48 were significantly lower for patients w ith baseline HIV-1 RNA > 100 000 copies/mL (P < 0.001). This difference in efficacy was consistent across trials of different treatment classes and NRTI backbones.
Authors: Lei Wang; Jing Tang; Andrew D Huber; Mary C Casey; Karen A Kirby; Daniel J Wilson; Jayakanth Kankanala; Jiashu Xie; Michael A Parniak; Stefan G Sarafianos; Zhengqiang Wang Journal: Eur J Med Chem Date: 2018-07-17 Impact factor: 6.514
Authors: Liesbeth Van Wesenbeeck; David D'Haese; Jeroen Tolboom; Hanne Meeuws; Dominic E Dwyer; Mark Holmes; Michael G Ison; Kevin Katz; Allison McGeer; Jerald Sadoff; Gerrit Jan Weverling; Lieven Stuyver Journal: Open Forum Infect Dis Date: 2015-11-03 Impact factor: 3.835
Authors: David I Dolling; Ruth L Goodall; Michael Chirara; James Hakim; Peter Nkurunziza; Paula Munderi; David Eram; Dinah Tumukunde; Moira J Spyer; Charles F Gilks; Pontiano Kaleebu; David T Dunn; Deenan Pillay Journal: BMC Infect Dis Date: 2017-02-21 Impact factor: 3.090
Authors: Françoise Barré-Sinoussi; Salim S Abdool Karim; Jan Albert; Linda-Gail Bekker; Chris Beyrer; Pedro Cahn; Alexandra Calmy; Beatriz Grinsztejn; Andrew Grulich; Adeeba Kamarulzaman; Nagalingeswaran Kumarasamy; Mona R Loutfy; Kamal M El Filali; Souleymane Mboup; Julio Sg Montaner; Paula Munderi; Vadim Pokrovsky; Anne-Mieke Vandamme; Benjamin Young; Peter Godfrey-Faussett Journal: J Int AIDS Soc Date: 2018-07 Impact factor: 5.396
Authors: Chloe Orkin; Kathleen E Squires; Jean-Michel Molina; Paul E Sax; Wing-Wai Wong; Otto Sussmann; Richard Kaplan; Lisa Lupinacci; Anthony Rodgers; Xia Xu; Gina Lin; Sushma Kumar; Peter Sklar; Bach-Yen Nguyen; George J Hanna; Carey Hwang; Elizabeth A Martin Journal: Clin Infect Dis Date: 2019-02-01 Impact factor: 9.079