Factors Associated With Viral Suppression and Drug Resistance in Children and Adolescents Living With HIV in Care and Treatment Programs in Southern Tanzania

Abstract

Background: Achieving viral suppression (VS) for persons living with HIV is key to reaching epidemic control. We assessed the prevalence of VS and the frequency of HIV drug resistance mutations (HIVDRM) among children and adolescents living with HIV (CALHIV) in the Southern Highland zone of Tanzania.

Methods: From 2019 to 2021, we enrolled CALHIV aged 1-19 years on ART for >6 months in a cross-sectional study. Participants had viral load (VL) testing; those with VL ≥ 1000 copies/mL underwent HIVDRM testing. VS (<1000 copies/mL) prevalence estimates were calculated and robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for associations with potential predictors of VS.

Results: Of 707 participants, 595 had VS (PR: 0.84, 95% CI: 0.81-0.87). Use of an integrase strand transfer inhibitor-containing regimen (aPR 1.15, 95% CI: 0.99-1.34), age 5-9 years (aPR 1.16, 95% CI: 1.07-1.26), and seeking care at a referral center (aPR 1.12, 95% CI: 1.04-1.21) were associated with VS. Factors inversely associated with VS included having one (aPR 0.82, 95% CI: 0.72-0.92) or two or more (aPR 0.79, 95% CI: 0.66-0.94) referrals for adherence counselling, and self-reporting missing one to two (aPR 0.88, 95% CI: 0.78-0.99) or three or more (aPR 0.77, 95% CI: 0.63-0.92) doses of ART in the past month. Of 74 participants with PRRT and INT sequencing done, 60 (81.1%) had HIVDRMs at the following frequencies: 71.6%, 67.6%, 1.4%, and 4.1% for major NNRTI, NRTI, PI, and INSTI respectively.

Conclusions: Higher rates of VS were observed in this cohort, and HIVDRMs were common in those without VS. This evidence supports ART optimization using dolutegravir-based regimens. However, better strategies to improve adherence are needed.

Keywords: children and adolescents; drug resistance; integrase inhibitors; viral suppression.

Figure 1.

Frequency of NNRTI, NRTI, PI, and INSTI resistance mutations among participants with viral load ≥1000 copies/mL. Plasma samples from participants with viral load ≥1000 copies/mL underwent sequencing of the Pol region using a laboratory-validated modification to the ViroSeq HIV-1 Genotyping System v2.0 (Abbott Molecular, Chicago, IL). Sequences were evaluated for major mutations conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) using the SmartGene Integrated Database Network System (SmartGene, Zug, Switzerland) to access mutation lists from the Stanford HIV Drug Resistance Database Version 8.8.0 (Stanford University, Stanford, CA). The prevalence of specific drug resistance mutations and categories of drug resistance mutations were calculated by dividing the number of participants with one or more mutations by the total number of participants genotyped.

Figure 2.

HIV-1 subtypes. HIV-1 subtype was inferred from the consensus evolutionary tree from SmartGene Integrated Database Network System, which utilizes the neighbor-joining method in MEGA4 software. The evolutionary distances were computed using the maximum composite likelihood method in units of the number of base substitutions per site. The tree was then generated by the neighbor-joining method from a nucleotide alignment.