High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa

摘要: Combination antiretroviral therapy (cART) has significantly reduced HIV morbidity and mortality in both developed developing countries. However, the sustainability of cART may be compromised by emergence viral drug resistance mutations (DRM) cellular persistence proviruses carrying these DRM. This is potentially a more serious problem resource limited settings. DRM were evaluated individuals with unsuppressed loads after first or multiple lines at two sites rural Limpopo, South Africa. Seventy-two patients of >1000 copies/ml recruited between March 2014 December 2015. Complete protease (PR) partial Reverse Transcriptase (RT) sequences amplified from plasma RNA paired proviral DNA 35 subjects. Amplicons directly sequenced to determine subtype using Stanford Drug Resistance Interpretation algorithm. Among 72 samples, 69 could PCR DNA. Sixty-five (94.2%) viruses C, while one was B (1.4%), recombinant K/C, C/B unclassified. Fifty-eight (84%) carried least DRM, 11 (15.9%) displayed no prevalence according class was: NRTI 60.8% NNRTI 65.2%, PI 5.8%. The most common DRMs were; M184V (51.7%), K103N (50%), V106M (20.6%), D67N (13.3%), K65R (12%). frequency tracked well use medications which predicted confer resistance. Interestingly, significant number subjects showed newer NNRTIs, etravirine (33%) rilpivirine (42%), are not yet available this setting. proportion mostly similar exception thymidine analogue (TAMs) D67N, K70R, K219QE; slightly prevalent than RNA. Subjects who had received for 5 years likely harbour >2 (p < 0.05) compared those treated shorter period. setting neighbouring urban We found very high Limpopo settings different durations treatment. higher reported dominance based late treatment supports regimens second line slight TAMs infected PBMCs virus requires further studies that should include suppressed virus. Such will improve our understanding pattern dynamics