Prevalence and Virologic Consequences of Transmitted HIV-1 Drug Resistance in Uganda

Abstract

Few reports have examined the impact of HIV-1 transmitted drug resistance (TDR) in resource-limited settings where there are fewer regimen choices and limited pretherapy/posttherapy resistance testing. In this study, we examined TDR prevalence in Kampala and Mbarara, Uganda and assessed its virologic consequences after antiretroviral therapy initiation. We sequenced the HIV-1 protease/reverse transcriptase from n = 81 and n = 491 treatment-naive participants of the Uganda AIDS Rural Treatment Outcomes (UARTO) pilot study in Kampala (AMU 2002(AMU -2004 and main cohort in Mbarara (MBA 2005(MBA -2010. TDR-associated mutations were defined by the WHO 2009 surveillance mutation list. Posttreatment viral load data were available for both populations. Overall TDR prevalence was 7% (Kampala) and 3% (Mbarara) with no significant time trend. There was a slight but statistically nonsignificant trend indicating that the presence of TDR was associated with a worse treatment outcome. Virologic suppression (£ 400 copies/ml within 6 months posttherapy initiation) was achieved in 87% and 96% of participants with wildtype viruses versus 67% and 83% of participants with TDR (AMU, MBA p = 0.2 and 0.1); time to suppression (log-rank p = 0.3 and p = 0.05). Overall, 85% and 96% of study participants achieved suppression regardless of TDR status. Surprisingly, among the TDR cases, approximately half still achieved suppression; the presence of pretherapy K103N while on nevirapine and fewer active drugs in the first regimen were most often observed with failures. The majority of patients benefited from the local HIV care system even without resistance monitoring. Overall, TDR prevalence was relatively low and its presence did not always imply treatment failure.

Prevalence and clinical impacts of HIV-1 intersubtype recombinants in Uganda revealed by near-full-genome population and deep sequencing approaches

“…A sample R script on the definitions and data extraction for virologic outcome is available in Gist (https://gist.github.com/guineverelee/public). Transmitted drug resistance data for this cohort was defined by the WHO list [16] and was previously published by our group [17]. Post-treatment drug resistance was defined using Stanford HIVdb [18].…”

“…The Uganda AIDS Rural Treatment Outcomes (UARTO) cohort consists of over 500 HIV-infected patients in Mbarara, Uganda, where HIV-1 subtypes A1 and D co-circulate [9–11]. Plasma samples were available before and after treatment initiation, and virologic and immunologic outcome data were collected for over seven years post-therapy.…”

HIV Drug Resistance Testing by High-Multiplex “Wide” Sequencing on the MiSeq Instrument

“…Plasma samples were collected from Canadian patients (n ϭ 759) or from participants in the Uganda AIDS Rural Treatment Outcomes (UARTO) study (n ϭ 349) (32). Samples from Canadian patients were collected in 2013 and 2014, as part of routine physician-ordered genotypic HIV drug resistance testing at the British Columbia Centre for Excellence in HIV/AIDS (BCCfE) (Vancouver, Canada).…”

“…Samples from Canadian patients were collected in 2013 and 2014, as part of routine physician-ordered genotypic HIV drug resistance testing at the British Columbia Centre for Excellence in HIV/AIDS (BCCfE) (Vancouver, Canada). Samples from the UARTO cohort consisted of baseline samples collected at the time of enrollment and samples collected for longitudinal virological monitoring following the initiation of ART, up to 7.5 years postinitiation (32). Plasma samples were stored at Ϫ20°C prior to extraction.…”

Brief Report: Should Abacavir Be a First-Line Alternative for Adults With HIV in Sub-Saharan Africa?

“…Participants were enrolled just prior to the start of ART, and were longitudinally monitored with study visits approximately every three months. Infections were predominantly subtype A1 (49%) and D (43%) [14]. The first 581 subjects enrolled underwent HLA-typing.…”