Challenges of scale-up to dolutegravir-based regimens in sub-Saharan Africa

Abstract

Objective: Evaluate the potential effectiveness of the implementation of dolutegravir (DTG)-based regimens in patients on failing current antiretroviral treatment (ART) given the high levels of nucleoside reverse transcriptase inhibitor (NRTI) resistance in Togo. Design: Patients on ART attending health facilities for routine follow-up visits and for whom HIV viral load test was performed were consecutively included. Methods: Protease, reverse transcriptase and integrase fragments were sequenced and analyzed for presence of drug resistance mutations for patients with viral load more than 1000 copies/ml. Results: Among 1681 patients, 320 (19.04%) had viral load more than 1000 copies/ml and 200 were tested for drug resistance mutations. Reverse transcriptase gene was successfully sequenced for 181/200 (90.5%) patients; 140/181 (77.4%) were resistant to NRTIs and non-NRTIs, 4/181 (2.2%) to NRTIs only and 18/181 (9.9%) to non-NRTIs only. Many viral strains accumulated mutations predicting resistance to NRTIs recommended in first and second-line DTG-based ART regimens. ART switch to a DTG-based regimen after viral load testing (viral load >1000 copies/ml) or blind switch without prior viral load testing to a new DTG-based first line, estimated 31% and 47.6% of patients to be potentially on functional DTG monotherapy respectively. Conclusion: Overall, our results predict that, at the scale of sub-Saharan Africa a significant proportion of patients could be on functional monotherapy. To achieve the third 90 of UNAIDS objectives, implementation of DTG-based regimens should be accompanied with an accelerated scaling up of access to viral load. Studies designed to quantify the implications of use of suboptimal DTG-based regimens are also needed.

Virologic Outcomes and ARV Switch Profiles 2 Years After National Rollout of Dolutegravir to Children Less Than 15 Years in Southern Mozambique

“…28,29 There has been concern that NRTI resistance associated with prior failing ART regimens may result in functional monotherapy with DTG in ART-experienced, virally unsuppressed individuals who switch to DTG and maintain the NRTI backbone of the failing regimen, potentially resulting in DTG failure and development of INSTI resistance. 30,31 However, meaningful differences in VLS between children who maintained or switched NRTI backbones at the time of the DTG switch were not observed in our study. This supports other evidence that found no difference among children virally unsuppressed before the single-drug switch to DTG when comparing small numbers on ABC, AZT or TDF-based backbones.…”

Tenofovir, Lamivudine, and Dolutegravir Among Rural Adolescents in Zimbabwe: A Cautionary Tale

“…20 Similarly, up to 31% and 47.6% of patients after VL failure and ART switch to a DTG-based or blind switching without prior VL testing respectively were estimated to be on functional DTG monotherapy in a recent (2020) study carried out in Togo. 21 Although, we found high rate of VS on TLD, one of the limitations of our study is that the study follow-up period was short (median = 6.9 months). Therefore, the long-term effect of DTG-based regimens on viral suppression in this cohort is yet to be evaluated.…”

Disparities in dolutegravir utilisation in children, adolescents and young adults (0-24 years) living with HIV. An analysis of the IeDEA Paediatric West African cohort

“…Suboptimal adherence to ART has long been identified as a major contributor to the development of drug resistance among people living with HIV [27,28]. Despite the higher genetic barrier in DTG, several studies have reported on the emergence of integrase inhibitor drug resistance and reduced efficacy in patients on DTG receiving functional monotherapy [29,30]. Viral failure in children and adolescents living with perinatally acquired HIV can be either the result of poor adherence, frequent in this population, or also often the consequence of pre-treatment drug resistance caused by suboptimal maternal ART regimens [31].…”