Abstract
BackgroundA comprehensive assessment of initial HIV-1 treatment success may inform study design and treatment guidelines.MethodsGroup-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.Outcome MeasuresAntiviral efficacy (undetectable plasma viral load) and premature cessation of therapy.Results114 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).ConclusionInitial 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).
Highlights
Combination antiretroviral therapy for human immunodeficiency virus (HIV)-1 infection typically comprises a ‘backbone’ – two nucleoside analogue reverse transcriptase inhibitors (NRTI) – and a third drug – either a non-nucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI) or an integrase strand-transfer inhibitor (INSTI).The United States Department of Health and Human Services (DHHS) guidelines form a major basis for HIV public policy in resource-rich settings
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)
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
Summary
When to commence cART remains guided by the clinical stage and CD4 lymphocyte count; pre-treatment plasma HIV viral load was removed as an indication for starting cART in 2007. While such recommendations arise from serial evaluation of individual studies by expert bodies, a systematic review of outcomes across multiple studies may reveal characteristics associated with success/failure, and so inform drug development, future study design, treatment guidelines and patient care. A comprehensive assessment of initial HIV-1 treatment success may inform study design and treatment guidelines
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
