Pre-treatment drug resistance data for infants newly diagnosed with HIV from nationally representative surveys conducted between 2011 and 2016 in nine sub-Saharan African countries showed high levels of resistance to NRTIs in first-line paediatric antiretroviral (ART) regimens, reports Aidsmap. Dr Seth Inzaule of the World Health Organisation (WHO) and colleagues at Tufts University School of Medicine – Boston, Malawi Ministry of Health – Lilongwe, Centres for Disease Control & Prevention – Lilongwe, University of Lomé, Lomé, Lagos University Teaching Hospital, College of Medicine of the University of Lagos, Instituto Nacional de Saúde, National Institute for Communicable Diseases –South Africa; Uganda Virus Research Institute, Amsterdam UMC, University of Amsterdam, Johns Hopkins University School of Medicine, have reported these findings.
Resistance was more common in surveys conducted after the introduction of lifelong maternal ART (Option B+). Infants whose mothers had taken ART during pregnancy had consistently higher levels of NRTI resistance than infants whose only exposure was infant prophylaxis.
Pre-treatment HIV drug resistance limits infants’ treatment options. It is linked to a poor response to first-line treatment and further accumulation of drug resistant mutations. Paediatric drug resistance may become a barrier to achieving the third pillar of 90-90-90.
Using data from the nine surveys undertaken in Eswatini, Uganda, Mozambique, Togo, Zimbabwe, Cameroon, South Africa, Nigeria and Malawi the authors looked at the prevalence of resistance to the NRTI drug class among ART naive infants aged 18 months or younger newly diagnosed with HIV through early infant diagnosis programmes.
These findings have implications for the paediatric regimens recommended in the 2019 WHO guidelines, specifically the integrase inhibitors raltegravir (for neonates) and dolutegravir (for children weighing more than 20 kg). Raltegravir, with its low genetic barrier for resistance, in newborns with NRTI resistance may compromise future use of dolutegravir.
The authors advise caution when considering using dolutegravir with abacavir and lamivudine/emtricitabine in young children in countries with a high prevalence of resistance to these drugs, given the limited evidence of dolutegravir in infants with NRTI resistance.
They recommend studies to estimate the prevalence of NRTI resistance in infants with mothers on dolutegravir-based regimens. Dolutegravir concentrations ingested through breastmilk may select for both dolutegravir and NRTI resistance.
Exposure of infants to antiretroviral drugs for prevention of mother-to-child transmission can induce resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). Data from nine national surveys of pretreatment drug resistance in children newly diagnosed with HIV show high levels of resistance to NRTIs included in first-line antiretroviral treatment (ART) regimens (dual abacavir-lamivudine/emtricitabine resistance). Additional research is needed to determine the impact of NRTI resistance on treatment response and optimize infant ART.
Inzaule, Seth C; Jordan, Michael R; Bello, George; Wadonda-Kabondo, Nellie; Mounerou, Salou; Mbulli, Innocent A; Akanmu, Sulaimon A; Vubil, Adolfo; Hunt, Gillian; Kaleebu, Pontiano; Mthethwa-Hleza, Simangele; Dzangare, Janet; Njukeng, Patrick; Penazzato, Martina; de Wit, Tobias F Rinke; Eshleman, Susan H; Bertagnolio, Silvia, for the Infant HIV Drug Resistance Survey Team
Full Aidsmap report