HIV-1 suppression and rare dolutegravir resistance in antiretroviral-experienced people with HIV in Liberia

Introduction

Antiretroviral (ARV) drug resistance among persons with HIV-1 (PWH) is a threat to ending the HIV epidemic^1,2. Since early 2000s, non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens have been recommended as first-line treatment for PWH in Africa. However, NNRTIs such as efavirenz (EFV) and nevirapine (NVP) are not optimal because of their high rates of toxicity and low genetic barriers to resistance. As of 2020, an estimated 24% of adults and 45% of infants with HIV in low- or middle-income countries (LMIC) on antiretroviral therapy (ART) had NNRTI resistance². In 2018, the World Health Organization (WHO) recommended switching first-line ART from an NNRTI-based regimen to the integrase strand transfer inhibitor (InSTI) dolutegravir (DTG) plus two nucleos(t)ide reverse transcriptase inhibitors (NRTIs)³. The WHO also recommended that HIV programs conduct routine surveillance of population-level HIV drug resistance (HIVDR) to inform public health decision-making². However, data on HIVDR are lacking for many countries in sub-Saharan Africa, which account for two-thirds of HIV cases globally. As of 2021, only 9 of the 54 countries in Africa, and none from West Africa, reported HIVDR data in adults to the WHO².

In Liberia, in the era of transition to DTG-based ART, prevalence of virologic failure and HIVDR have not been studied. Prior studies from Monrovia, which included small sample sizes and were conducted when plasma viral load (pVL) monitoring was unavailable, reported that 5.9% of ART-naïve patients, and >60% of those with viraemia while on first-line NNRTI-based therapy, had HIVDR^4,5. In 2018, following WHO’s recommendation, a fixed-dose combination of DTG, tenofovir (TDF), and lamivudine (3TC) was introduced as first-line therapy in Liberia. In addition, patients who were already on ART were switched to this regimen, regardless of pVL. Switching ART regimens without information on pVL or genotypic resistance profile may result in suboptimal treatment response. To date, despite an increasing proportion of Liberian PWH on ART (53% as of 2022)^6,7 and receiving pVL monitoring, challenges persist. Some clinics still lack resources for routine pVL testing, and drug resistance testing is unavailable^7,8. In PWH with virologic failure, little is known in Liberia about the proportion with HIVDR and, consequently, the appropriate intervention. Achieving the third 95 (95%...