Viral Suppression After Transition From Nonnucleoside Reverse Transcriptase Inhibitor- to Dolutegravir-based Antiretroviral Therapy

A Prospective Cohort Study in Lesotho (DO-REAL Study)

Jennifer A. Brown; Bienvenu L. Nsakala; Kuena Mokhele; Itumeleng Rakuoane; Josephine Muhairwe; Lorena Urda; Alain Amstutz; Nadine Tschumi; Thomas Klimkait; Niklaus D. Labhardt

Disclosures

HIV Medicine. 2022;23(3):287-293. 

In This Article

Abstract and Introduction

Abstract

Objectives: Since 2018, the World Health Organization has recommended dolutegravir (DTG)-containing antiretroviral therapy (ART) for most people living with HIV. Country programmes across Africa have subsequently transitioned from other, mostly nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART to DTG-based ART. This study aims to assess the virological impact of programmatic transitioning to DTG-based ART in Lesotho.

Methods: The prospective Dolutegravir in Real-Life in Lesotho (DO-REAL) cohort enrols people living with HIV initiating or transitioning to DTG-based ART in Lesotho. Here, we present data from participants who transitioned from NNRTI- to DTG-based ART between February and December 2020. Blood samples collected at transition and at 16 weeks' follow-up (window 8–32 weeks) were used for viral load (VL) and resistance testing.

Results: Among 1347 participants, follow-up data was available for 1225. The majority (60%) were female, median age at transition was 47 years [interquartile range (IQR): 38–56], and median (IQR) time since ART initiation was 5.9 (3.5–9.0) years. Among those with complete VL data, the rate of viral suppression to < 100 copies/mL was 1093/1116 (98%) before, 1073/1116 (96%) at, and 1098/1116 (98%) after transition. Even among those with a VL ≥ 100 copies/mL at transition, 42/44 (95%) achieved suppression to < 100 copies/mL at follow-up. Seven participants had a VL ≥ 1000 copies/mL at follow-up and did not harbour any integrase mutations associated with resistance to DTG.

Conclusions: The high levels of viral suppression observed are encouraging regarding virological outcomes upon programmatic transitioning from NNRTI- to DTG-based ART.

Introduction

Antiretroviral therapy (ART) containing dolutegravir (DTG) is recommended as the preferred regimen type of most people living with HIV.[1,2] DTG-based ART leads to superior[3–5] or non-inferior[6–9] virological outcomes and faster viral suppression[3,4,7] compared with commonly available NNRTI-based regimens, has a high barrier to development of drug resistance,[3,10] and a favourable tolerability profile.[3] For these reasons, countries including Lesotho are recommending DTG-containing regimens not only for people newly diagnosed with HIV, but also for people transitioning from other, mostly nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens to DTG-containing ART.[11]

While DTG-containing ART has good virological outcomes when used in triple and dual drug regimens,[3–10,12,13] DTG monotherapy is associated with the development of drug resistance and treatment failure,[10] and should therefore be restricted to special circumstances.[14] This has caused concerns that DTG functional monotherapy among ART-experienced people – which could occur through just substituting the NNRTI for DTG in the case of viral resistance to the other two drugs in a three-drug regimen – might likewise adversely impact treatment outcomes.[10,15] Moreover, instances of mutations associated with resistance to DTG have been described in randomized trials even in the context of triple therapy in people with and without prior exposure to first-generation integrase strand transfer inhibitors (INSTIs).[10,16]

Consequently, there is uncertainty regarding the optimal modality for the roll-out of DTG, with open questions including the requirement for previous viral suppression, the viral load (VL) threshold allowing for transition, and the timing of VL measurement before transition. This study aims to assess virological outcomes upon programmatic transitioning from NNRTI- to DTG-based ART in a routine care setting in Lesotho, southern Africa.

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