There are limited data on the effectiveness of dolutegravir (DTG)-based combination antiretroviral therapy (ART) in real-life settings in southern Africa where HIV-1 subtype C predominates. We report a patient infected with HIV-1 subtype C on DTG-based ART previously exposed to raltegravir who developed multidrug resistance mutations to four antiretroviral classes. There is need for drug resistance monitoring and clinical vigilance to ensure effectiveness of HIV treatment programs even in the era of DTG-based ART.

Maintaining viral load suppression in people living with HIV (PLWHIV) is critical to ensure both the health of PLWHIV and prevent onward transmission of HIV to sexual partners [1–3]. Despite major advances in the development of antiretroviral (ARV) drugs and ARV therapy (ART) treatment guidelines [4–6], low and middle-income countries (LMICs) continue to face challenges such as poor ARTadherence, limited HIV care specialists, drug stock-outs, lack of ancillary healthcare services and so on [7–9]. These barriers to effective ART may lead to development of extensive HIV-1 drug resistance.

Dolutegravir (DTG) has recently been introduced as part of the first-line ART regimen in Botswana and may soon be adopted by other countries in sub-Saharan Africa (SSA) [10,11]. Therefore, there is a need to monitor the development of integrase strand transfer inhibitor (INSTI) resistance mutations. We report a case of a four-class drug-resistant HIV-1 subtype C in a 51-year-old man currently on DTG-based ART with persistent viremia.

Chart reviews of treatment-experienced patients not virologically suppressed while on salvage ART therapy were conducted at a local tertiary hospital as part of the Botswana Epidemiological ART Treatment (BEAT) cohort study. A case-file reported herein was identified and an analysis of the patient’s medical record was conducted with information gathered from September 2003 to November 2017. The patient provided written informed consent to complete the analysis for publication, and the BEAT study is approved by the human research and development council of Botswana.

Genotypic resistance testing (GRT) was performed using Sanger sequencing of the pol and envelope genes. Sequences obtained were assessed for drug resistance mutations using the Stanford University HIV Drug Resistance Database (https://hivdb.stanford.edu), International Antiviral Society USA 2017 mutational list [12] and coreceptor usage was determined using with geno2pheno_[coreceptor] [13]. All sequences generated were submitted to GenBank under accession numbers MG989439-MG989443, MH004049 and MH004050.

The patient was initiated on zidovudine (AZT), lamivudine and nevirapine on September 2003 as per the 2002 Botswana National ART guidelines. Apart from persistent viremias, his 14-year follow-up history has been clinically uneventful and devoid of opportunistic infections.

He intermittently achieved virological suppression between September 2003 and April 2014 (six HIV-1 RNA levels <400 copies/ml out of 67 tests) (Fig. 1). His ARTregimens while virologically suppressed were AZT/tenofovir (TDF)/ritonavir-boosted lopinavir from April 2007 and TDF/emtricitabine/ritonavir-boosted darunavir/raltegravir for the remaining aviremic episodes from February 2010. The majority of viral load revealed virological failure with viral load ranging between 2.61 log₁₀ and 5.88 log₁₀ copies/ml (Fig. 1). Nine switches in ARV medications were made from September 2003 to November 2017 (Fig. 1). Adherence to clinic appointments and medications was suboptimal, and he experienced one episode of drug stock-out of ARVs (darunavir) for approximately 2 weeks in March 2012. His social circumstances remained challenging, making it difficult for him to be adherent to his medications despite multiple counseling and adherence support sessions from healthcare providers

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