Efficacy of initial antiretroviral therapy for HIV-1 infection in adults: a systematic review and meta-analysis of 114 studies with up to 144 weeks' follow-up.
BACKGROUND
A comprehensive assessment of initial HIV-1 treatment success may inform study design and treatment guidelines.


METHODS
Group-based, systematic review and meta-analysis of initial antiretroviral therapy studies, in adults, of ≥ 48 weeks duration, reported through December 31, 2012. Size-weighted, intention-to-treat efficacy was calculated. Parameters of study design/eligibility, participant and treatment characteristics were abstracted. Multivariable, random effects, linear regression models with backwards, stepwise selection were then used to identify variables associated with efficacy.


METHODS
Antiviral efficacy (undetectable plasma viral load) and premature cessation of therapy.


RESULTS
114 studies were included (216 treatment groups; 40,124 participants; mean CD4 count 248 cells/µL [SD 81]; mean HIV-1 plasma viral load log10 4.9 [SD 0.2]). Mean efficacy across all groups was 60% (SD 16) over a mean 82 weeks' follow-up (SD 38). Efficacy declined over time: 66% (SD 16) at 48 weeks, 60% (SD 16) at 96 weeks, 52% (SD 18) at 144 weeks. The most common reason for treatment cessation was participant decision (11%, SD 6.6). Efficacy was higher with 'Preferred' than 'Alternative' regimens (as defined by 2013 United States antiretroviral guidelines): 75% vs. 65%, respectively, difference 10%; 95%CI 7.6 to 15.4; p<0.001. In 98 groups (45%) reporting efficacy stratified by pre-treatment viral load (< or ≥100,000 copies/mL), efficacy was greater for the lower stratum (70% vs. 62%, respectively, difference 8.4%; 95%CI 6.0 to 10.9; p<0.001). This difference persisted within 'Preferred' regimens. Greatest efficacy was associated with use of tenofovir-emtricitabine (vs. other nucleoside analogue backbones) and integrase strand transfer inhibitors (vs. other third drug classes).


CONCLUSIONS
Initial antiretroviral treatments for HIV-1 to date appear to have suboptimal long-term efficacy, but are more effective when commenced at plasma viral loads <100,000 copies/mL. Rising viral load should be considered an indication for starting treatment. Integrase inhibitors offer a treatment advantage (vs. other third drug classes).
Clinical Research Program, St. Vincent's Centre for Applied Medical Research, Sydney, Australia.
Frederick J
FJ
Lee
The Kirby Institute, University of New South Wales, Sydney, Australia.
Janaki
J
Amin
Clinical Research Program, St. Vincent's Centre for Applied Medical Research, Sydney, Australia; HIV, Immunology and Infectious Diseases Unit, St. Vincent's Hospital, Sydney, Australia.
Andrew
A
Carr
D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D016014:Linear Models; D015999:Multivariate Analysis; D017410:Practice Guidelines as Topic; D016896:Treatment Outcome; D014481:United States; D014483:United States Dept. of Health and Human Services; D019562:Viral Load
D044966:Anti-Retroviral Agents