First-Line Antiretroviral Therapy Less Effective in Patients With 100,000 HIV-1 Copies/mL or More at Baseline: Presented at AIDS 2012

By Brian Hoyle
WASHINGTON, DC -- July 27, 2012 -- First-line antiretroviral (ART) compounds have poor efficacy against HIV-1 infection at 48 weeks of treatment in patients with a baseline HIV-1 ribonucleic acid (RNA) level of 100,000 copies/mL or greater, researchers reported here at the 19th AIDS Conference.
The findings were consistent in a meta-analysis involving over 12,000 patients treated with a broad array of ART compounds with different nucleoside analogues and treatment classes.
“In this meta-analysis of 21 randomised trials, patients with baseline HIV-1 RNA levels ·100,000 copies/mL were significantly less likely to have full suppression to The trials were identified in a MEDLINE search of articles that addressed ART efficacy at a baseline HIV-1 RNA level under 100,000 copies/mL (designated the low subgroup) versus 100,000 copies/mL or higher (the high subgroup). The standardised efficacy endpoint used in the meta-analysis was the percentage of patients with HIV-1 RNA levels under 50 copies/mL at week 48 of treatment. The statistical analysis was concerned with the association between the baseline condition and the efficacy endpoint.
The assessed studies involved the nucleoside analogues tenofovir, emtricitabine (FTC), lamivudine (3TC), zidovudine (ZDV), stavudine (d4T), and abacavir (ABC); the non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz, nevirapine, etravirine, and rilpivirine; the protease inhibitors (PIs) lopinavir/ritonavir (r), darunavir/r, atazanavir/r, and fosamprenavir/r; the integrase inhibitors raltegravir and elvitegravir/cobicistat; and the CCR5 antagonist maraviroc.
Only 8 trials evaluated NNRTI-based treatment, 8 evaluated PI-based treatment, and 5 evaluated different treatment classes. Seven of the trials included TDF/FTC as the NRTI backbone, while 12 included either ABC/3TC (n = 7), ZDV/3TC (n = 4), or d4T/3TC (n = 1).
Across all trials, HIV-1 RNA was reduced to less than 50 copies/mL at week 48 in 5,322 of 6,814 (81.5%) patients in the low subgroup and in 3,949 of 5,556 (72.6%) patients in the high subgroup.
Stratifying by trial revealed an absolute difference in efficacy between the low and high subgroups of 7.3% (95% confidence interval [CI], 5.9%-8.9%, P <.001 this subgroup-related efficacy difference held in the nnrti-based trials ci and pi-based integrase- or ccr5-based> The difference in efficacy was maintained when including only the 7 trials using TDF/FTC as the NRTI backbone (difference = 9.8%, 95% CI, -7.3% to -12.3%). There was no evidence for heterogeneity of this difference between trials concerning the classes of drugs used or the NRTI backbone.
The reduced treatment efficacy with high viral load and the lack of discernible benefit between different NRTI backbones and treatment classes indicates that the outcome in terms of viral suppression for those with a high baseline viral load is not optimistic.
[Presentation title: Effects of Baseline HIV-1 RNA Levels on the 48 Week Efficacy of First-Line Antiretroviral Treatment for HIV: A Meta-Analysis of 10,962 Patients in 19 Randomised Clinical Trials. Abstract TUPE085]

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