Antiretroviral adherence, elevated viral load and drug resistant mutations in HIV-infected women initiating treatment in pregnancy: a nested case-control study.

BACKGROUND: Elevated viral load (VL) early after antiretroviral therapy (ART) initiation appears frequently in pregnant and postpartum women living with HIV, however the relative contributions of pre-ART drug-resistant mutations (DRM) versus non-adherence in the aetiology of elevated VL are unknown.

METHODS: Within a cohort of women initiating ART during pregnancy in Cape Town, South Africa, we compared women with elevated VL after initial suppression (cases, n=80) incidence-density matched to women who maintained suppression over time (controls, n=87). Groups were compared on pre-ART DRM and detection of antiretrovirals in stored plasma.

RESULTS: The prevalence of pre-ART DRM was 10% in cases and 5% in controls (adjusted odds ratio [OR], 1.53; 95% confidence intervals [CI]:0.40-5.86); all mutations were to non-nucleoside reverse transcriptase inhibitors. At the time of elevated VL, 19% of cases had antiretrovirals detected in plasma, compared to 87% of controls who were suppressed at a matched time point (aOR, 131.43; 95% CI:32.75-527.40). Based on these findings we estimate that <10% of all elevated VL in the cohort may be attributable to pre-ART DRM versus >90% attributable to ART non-adherence.

CONCLUSION: DRM account for a small proportion of all elevated VL among women occurring in the 12 months after ART initiation during pregnancy in this setting, with non-adherence appearing to drive most episodes of elevated VL. Alongside the drive for access to more robust antiretroviral agents in resource-limited settings there is an ongoing need for effective strategies to support ART adherence in this patient population.