Rapid accumulation of nonnucleoside reverse transcriptase inhibitor-associated resistance: evidence of transmitted resistance in rural South Africa

Abstract

In a large cohort in rural South Africa, 73% of subtype-C-infected patients initiating highly active antiretroviral therapy achieved viral suppression. In patients with subsequent virological failure, an unexpected, rapid accumulation of nonnucleoside reverse transcriptase inhibitor-associated mutations was observed, whereas no thymidine analogue-associated mutations emerged. It appeared that several patients had drug-associated mutations prior to starting antiretrovirals, suggesting that transmission of resistance may have contributed to the accumulation of nonnucleoside reverse transcriptase inhibitor-mutations. Importantly, monitoring of HIV-RNA and prompt switch of treatment may prevent development of thymidine analogue-associated mutations.

HIV-1 Drug Resistance Mutations Are Present in Six Percent of Persons Initiating Antiretroviral Therapy in Lusaka, Zambia

“…19 Population surveys [7][8][9][10][11][12] and mathematical models 20 to date have reported low levels of drug-resistant infections in African populations with increasing selective ARV drug pressure, but recent preliminary reports have suggested transmission of resistant strains directly after national ARV rollout programs. 21,22 The predominance of NNRTI-associated DRMs (mostly Y181C and K103N/S) in this baseline study probably results from the widespread use of NNRTIs as part of standard first-line ART and PMTCT regimens. Most solitary NNRTIassociated DRMs cause a complete loss of activity of efavirenz and nevirapine, 23 which may compromise the initial response to the standard first-line therapy.…”

Accumulation of HIV Drug Resistance Mutations in Patients Failing First-Line Antiretroviral Treatment in South Africa

“…Patients who experienced toxicity to d4T were changed to zidovudine (AZT, n = 10) or tenofovir (TDF, n = 2). All patients were infected with HIV-1 subtype C. For 37 patients with prior VL tests, the median time between first detection of viremia and treatment switch was 7 months (IQR: [4][5][6][7][8][9][10][11][12][13].…”

“…[4][5][6] In contrast to other countries in sub-Saharan Africa, studies from South Africa have reported fewer thymidine analogue mutations (TAMs) at failure of first-line ART, likely to be related to the use of viral load (VL) monitoring in the public sector program. [5][6][7] A study from Malawi described complex resistance profiles in patients diagnosed with clinical and/or immunological treatment failure. 8 Similarly, a metaanalysis has also revealed a higher frequency of genotypic resistance in less frequently monitored patients in resourcelimited settings.…”

Highly Active Antiretroviral Therapy is Associated with Decreased Incidence of Sexually Transmitted Diseases in a Taiwanese HIV-Positive Population

“…16,17 A drug-resistant virus can emerge when patients do not adhere to HAART, leading to transmitted resistance and hindering the effect of preventive treatment. 18,19 In Taiwan, a cross-sectional report revealed that 56% of HIV-positive patients, especially men who have sex with men (MSM), practiced unprotected sexual behavior. 20 Other investigators in southern Taiwan showed that 17% of HIVpositive patients relapsed to sexual risk behavior after 1 year of enrollment in a case management (CM) program, and that the incidence for syphilis was 5.8 cases per 100 patient-years.…”