Pretreatment Human Immunodeficiency Virus (HIV) Drug Resistance Among Treatment-Naive Infants Newly Diagnosed With HIV in 2016 in Namibia: Results of a Nationally Representative Study

Abstract

Background The World Health Organization (WHO) recommends routine surveillance of pretreatment HIV drug resistance (HIVDR) in children <18 months of age diagnosed with HIV through early infant diagnosis (EID). In 2016, 262 children <18 months of age were diagnosed with HIV in Namibia through EID. Levels of HIVDR in this population are unknown. Methods In 2016, Namibia surveyed pretreatment HIVDR among children aged <18 months following WHO guidance. Reverse transcriptase, protease, and integrase regions of HIV-1 were genotyped from remnant dried blood spot specimens from all infants diagnosed with HIV in Namibia in 2016. HIVDR was predicted using the Stanford HIVdb algorithm. Results Of 262 specimens genotyped, 198 HIV-1 protease and reverse transcriptase sequences and 118 HIV-1 integrase sequences were successfully amplified and analyzed. The prevalence of efavirenz/nevirapine (EFV/NVP), abacavir (ABC), zidovudine, lamivudine/emtricitabine (3TC/FTC), and tenofovir (TDF) resistance was 62.6%, 17.7%, 5.6%, 15.7%, and 10.1%, respectively. No integrase inhibitor resistance was detected. Conclusions The high level of EFV/NVP resistance is unsurprising; however, levels of ABC and TDF resistance are amongst the highest observed to date in infants in sub-Saharan Africa. The absence of resistance to dolutegravir (DTG) is reassuring but underscores the need to further study the impact of ABC and 3TC/FTC resistance on pediatric protease inhibitor and DTG-based regimens and accelerate access to other antiretroviral drugs. Results underscore the need for ART optimization and prompt management of high viral loads in infants and pregnant and breastfeeding women.

Optimizing antiretroviral therapy for children living with HIV: Experience from an observational cohort in Lesotho

“…Overall, 82.2% of participants attained viral suppression with a notably higher proportion (94.7%) of viral suppression seen among children who transitioned to DTG. Viral resistance to NVP and NNRTIs in general, has been widely known for the last two decades [6,[24][25][26], and yet, as shown in this cohort, nearly half of the children were initiated on EFV and NVP and continued to depend on these suboptimal medications in the absence of more effective child-appropriate options. ART optimization for children has traditionally lagged behind that of adults partly because evidence on the effectiveness and safety of new agents often comes from trials that exclude children; however, even when the evidence is available, development of appropriate formulations for children and ensuring their availability in places where they are needed often comes with additional delays.…”

Brief Report: Characterizing HIV Drug Resistance in Cases of Vertical Transmission in the VESTED Randomized Antiretroviral Treatment Trial

“…Given the duration of HIV infection sustained by children, preserving HIV susceptibility to NNRTI provides an additional rationale for utilization of more potent and long-acting antiretrovirals or antibodies for infant prophylaxis. 7,36,37,[94][95][96][97][98][99]…”