Characterization of human immunodeficiency virus drug-resistance mutations among individuals with low-level-viremia in low-income and middle-income countries: A meta-analysis

Abstract

BACKGROUND

Low-level viremia (LLV) defined as [human immunodeficiency virus (HIV)-RNA 51-999 copies/mL] has been associated with an increased risk of drug resistance and treatment failure. Advances in next-generation sequencing enabled the detection of drug resistance mutations (DRM) among people with LLV. However, evidences remain limited in low-income and middle-income countries (LMIC) where surveillance is most needed to inform global epidemic control strategies.

AIM

To determine the prevalence of HIV DRM among people living with HIV who have LLV in low- and middle-income countries.

METHODS

PubMed, Cochrane Library, and EMBASE were systematically searched for articles published between January 2015 and May 2025. Studies were included if they reported DRM among adolescents and/or adults with LLV in LMIC. Mutations were interpreted using Stanford University HIV Drug Resistance Database. Prevalence of DRM was computed as the proportion of resistance mutations among successfully sequenced samples. Pooled estimates of resistance mutation and 95%CI were calculated using random-effects models with stratified analyses comparing mutations by geographic location (Africa vs Asia).

RESULTS

Twenty studies including 7613 people with LLV were included. Of these, 5252 (73.9%) had their samples successfully sequenced. Eleven studies were from Africa and nine from Asia. Overall, the pooled prevalence of DRM was 50.4% (95%CI: 38.3-62.5) with a significantly higher prevalence observed among Africa studies compared to Asia’s (58.0% vs 40.7%; P < 0.0001). The prevalence of mutations associated with nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor were 44.6% (95%CI: 34.8-54.4), and 50.9% (95%CI: 41.4-60.4) respectively and were significantly higher in Africa than in Asia. Protease inhibitor associated mutations were also common in Africa than in Asia (7.3% vs 4.1%; P < 0.001), though the overall prevalence remains low.

CONCLUSION

Most individuals with LLV have resistance mutations and remain on a failed regimen over an extended period. Because resistance testing is not routinely performed in LMIC, lowering the viral failure threshold may improve timely switching to effective regimens, preserve treatment options, and reduce resistance accumulation in high HIV burden regions.

Keywords: Low level viremia; Antiretroviral therapy; Drug resistance mutations; Human immunodeficiency virus; Low-income and middle-income countries

Core Tip: Next-generation sequencing enabled successful sequencing and determined drug resistance mutations (DRM) among people with low-level viremia (LLV). Data on the DRM among people with LLV in low-income and middle-income countries (LMIC) is limited and may help achieve human immunodeficiency virus epidemic control. This systematic review and meta-analysis analyzed 7613 people living with human immunodeficiency virus who had LLV from 20 studies conducted in LMIC between 2015 and 2025. Overall, the pooled prevalence of DRM was 50.4%. Pooled prevalence of nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor and protease inhibitor-associated mutations were 44.6%, 50.9% and 5.1% respectively. In LMIC, most patients with LLV have resistance mutations and remain on a failed regimen over an extended period. Because resistance testing is not routinely performed in LMIC, lowering the viral failure threshold may hasten patients switch to effective drugs.