Abstract
ObjectivesThe resistance profiles of patients receiving long-term ART in sub-Saharan Africa have been poorly described. This study obtained a sensitive assessment of the resistance patterns associated with long-term tenofovir-based ART in a programmatic setting where virological monitoring is yet to become part of routine care.MethodsWe studied subjects who, after a median of 4.2 years of ART, replaced zidovudine or stavudine with tenofovir disoproxil fumarate while continuing lamivudine and an NNRTI. Using deep sequencing, resistance-associated mutations (RAMs) were detected in stored samples collected at tenofovir introduction (T0) and after a median of 4.0 years (T1).ResultsAt T0, 19/87 (21.8%) subjects showed a detectable viral load and 8/87 (9.2%) had one or more major NNRTI RAMs, whereas 82/87 (94.3%) retained full tenofovir susceptibility. At T1, 79/87 (90.8%) subjects remained on NNRTI-based ART, 5/87 (5.7%) had introduced lopinavir/ritonavir due to immunological failure, and 3/87 (3.4%) had interrupted ART. Whilst 68/87 (78.2%) subjects maintained or achieved virological suppression between T0 and T1, a detectable viral load with NNRTI RAMs at T0 predicted lack of virological suppression at T1. Each treatment interruption, usually reflecting unavailability of the dispensary, doubled the risk of T1 viraemia. Tenofovir, lamivudine and efavirenz selected for K65R, K70E/T, L74I/V and Y115F, alongside M184V and multiple NNRTI RAMs; this resistance profile was accompanied by high viral loads and low CD4 cell counts.ConclusionsViraemia on tenofovir, lamivudine and efavirenz led to complex resistance patterns with implications for continued drug activity and risk of onward transmission.
Highlights
Viraemia on tenofovir, lamivudine and efavirenz led to complex resistance patterns with implications for continued drug activity and risk of onward transmission
Access to ART has been increasing in sub-Saharan Africa (SSA), where an estimated 25.5 million people live with HIV, of whom 36% (Western and Central Africa) to 61% (Eastern and Southern Africa) were receiving treatment in 2016.1 WHO recommends a public health approach to managing HIV in SSA, based upon rapid treatment initiation regardless of CD4 cell counts, and use of standardized regimens for first-line and second-line therapy.[2]
In 2009, WHO recommended phasing out stavudine in favour of less-toxic NRTIs, including tenofovir disoproxil fumarate.[3]
Summary
Access to ART has been increasing in sub-Saharan Africa (SSA), where an estimated 25.5 million people live with HIV, of whom 36% (Western and Central Africa) to 61% (Eastern and Southern Africa) were receiving treatment in 2016.1 WHO recommends a public health approach to managing HIV in SSA, based upon rapid treatment initiation regardless of CD4 cell counts, and use of standardized regimens for first-line and second-line therapy.[2]. NRTIs. In 2009, WHO recommended phasing out stavudine in favour of less-toxic NRTIs, including tenofovir disoproxil fumarate ( referred to as tenofovir).[3] Current WHO guidelines place tenofovir, in combination with lamivudine or emtricitabine, as the preferred NRTI backbone for the treatment of HIV infection in SSA, including the treatment of highly prevalent coinfection with HBV.[4] Use of tenofovir as part of ART has been increasing as a result.[5] In 2013, WHO recommended that plasma viral load monitoring should be adopted in SSA to guide treatment changes, replacing reliance on CD4 cell counts and clinical indicators of treatment failure.[6] implementation of viral load monitoring varies across the region, and even in settings with access to testing delays in identifying treatment failure are commonly reported.[7,8,9,10] HIV-positive individuals in SSA face additional
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