Impact of Pre-antiretroviral Therapy CD4 Counts on Drug Resistance and Treatment Failure: A Systematic Review.

Abstract

The continuous rising of HIV drug resistance in low- and middle-income countries and its impact on treatment failure is a growing threat for the HIV treatment response. This review aimed to document pre-antiretroviral therapy (ART) CD4 counts, emerging drug resistance, and treatment failure in HIV-infected individuals initiating ART. We performed an online search in PubMed, Embase, Web of Science, African Index Medicus, Cochrane library, and The National Institute for Health Clinical Trials Registry of relevant articles published from January 1996 to June 2019. Of 1755 original studies retrieved, 28 were retained for final analysis. Treatment failure varied between 5% (95% confidence interval [CI]: 2.7-7.4) and 72% (95% CI: 55-89.6), while resistance varied between 1% (95% CI: 0.47-1.5) and 48% (95% CI: 28.4-67.6). Participants with a pre-ART CD4 count below 200 cell/μl and low adherence showed higher percentages of resistance and failure, while those with CD4 count above 200 showed lower resistance and failure regardless adherence levels. Most frequent resistance mutations included the M184I/V for the nucleoside reverse-transcriptase inhibitors (NRTIs), K103N, and Y181 for the non-NRTIs (NNRTIs), and L90M for the Protease inhibitors. Pre-ART CD4 count and adherence to treatment could play a key role in reducing drug resistance and treatment failure. The increased access to ART in resources limited settings should be accompanied by regular CD4 count testing, drug resistance monitoring, and continuous promotion of adherence. In addition, the rising of resistance mutations associated with NRTIs and NNRTIs, suggest that alternative ART regimens should be considered. (AIDS Rev. 2020;22:<FP>-0).