Objectives: To assess viral suppression rates, to assess prevalence of acquired HIV drug resistance and to characterize the spectrum of HIV-1 drug resistance mutations (HIV-DRM) in HIV-1-infected patients in a rural Tanzanian HIV cohort.

Methods: This was a cross-sectional study nested within the Kilombero and Ulanga Antiretroviral Cohort. Virological failure was defined as HIV-1 RNA ≥50 copies/mL. Risk factors associated with virological failure and with the development of HIV-DRM were assessed using logistic regression.

Results: This study included 304 participants with a median time on ART of 3.5 years (IQR = 1.7–5.3 years); 91% were on an NNRTI-based regimen and 9% were on a boosted PI-based regimen. Viral suppression was observed in 277/304 patients (91%). Of the remaining 27 patients, 21 were successfully genotyped and 17/21 (81%) harboured ≥1 clinically relevant HIV-DRM. Of these, 13/17 (76.5%) had HIV-1 plasma viral loads of >1000 copies/mL. CD4 cell count <200 cells/mm³ at the time of recruitment was independently associated with a close to 8-fold increased odds of virological failure [adjusted OR (aOR) = 7.71, 95% CI = 2.86–20.78, P < 0.001] and with a >8-fold increased odds of developing HIV-DRM (aOR = 8.46, 95% CI = 2.48–28.93, P = 0.001).

Conclusions: High levels of viral suppression can be achieved in rural sub-Saharan Africa when treatment and care programmes are well managed. In the absence of routine HIV sequencing, the WHO-recommended threshold of 1000 viral RNA copies/mL largely discriminates virological failure secondary to HIV-DRM.