Genotypic resistance testing (GRT) is recommended after virologic failure in resource-rich settings. By contrast, guidelines in sub-Saharan Africa promote adherence support and repeat virologic monitoring, in the absence of GRT, to guide treatment.
We conducted an open-label, randomized controlled trial to assess whether GRT improved virologic suppression after first-line antiretroviral therapy (ART) failure in sub-Saharan Africa. We enrolled adults in ambulatory care in South Africa and Uganda on first-line ART with an HIV-1 RNA viral load (VL)>1,000 copies/mL. We excluded those currently eligible for second-line or with prior known drug resistance. Individuals were randomized 1:1 to standard-of-care (SOC), with adherence counseling and virologic monitoring to determine management, or immediate GRT, with therapeutic decision making by clinic staff trained in GRT interpretation. The primary outcome was achievement of VL<200 copies/mL 9 months after enrollment. Analyses were intent-to-treat such that those deceased or lost from care were considered failures. Secondary outcomes included suppression less than assay, suppression while maintaining first-line ART, retention in care, mortality, and presence of drug resistance at study conclusion among those with a VL>1,000 copies/mL.
We enrolled 840 participants, divided equally by country and sex. The median age was 37 years, median ART duration was 3 years, and 82% were taking efavirenz-based ART. There was no difference in the proportion in care and achieving a VL<200 copies/mL at 9 months by arm (SOC: 256/423, 61%; RT: 263/417, 63%, OR 1.11, 95%CI 0.83-1.49, P=0.46). Results were similar in pre-defined sub-groups (Figure). Those with a VL>1,000 copies/mL at 9 months in the SOC arm were more likely to have drug resistance detected (SOC: 75/103 75%; GRT: 46/82 56%, OR 2.39, 95%CI 1.28-4.48, P=0.01), but we found no difference in 9-month mortality (SOC: 8/423, 2%; GRT: 14/417 4%, OR 0.55, 95% 0.23-1.33, P=0.19) or other secondary outcomes.
In public clinics in sub-Saharan Africa, the addition of GRT to routine care did not improve achievement of virologic suppression 9 months after first-line ART failure but did lower the likelihood of drug resistance in those with persistent viremia. Interventions that improve management of ART failure remain elusive and are of particular importance to enable prompt transition from efavirenz-based to dolutegravir-based therapy in the region.
