STUDY REVEALS HIGH PREVALENCE OF ANTIRETROVIRAL DRUG RESISTANCE AMONG CHILDREN LIVING WITH HIV AND THEIR MOTHERS
A study conducted at the Manhiça Health Research Centre (CISM) identified a high prevalence of mutations associated with antiretroviral drug resistance among children living with HIV and their mothers, highlighting the importance of making drug resistance testing and treatment response monitoring more accessible, particularly in low-income settings. The article published in the Pediatric Infectious Disease Journal analysed data from 79 children living with HIV, of whom 31 had valid results from genetic drug resistance tests. Samples from 10 of their mothers were also analysed.
The participants were part of a subcohort of the EARTH (Early Anti-Retroviral Treatment in Children) study, conducted under the international EPIICAL consortium (Early-treated Perinatally HIV-infected Individuals: Improving Children's Actual Life with Novel Immunotherapeutic Strategies).
The study involved collaboration between CISM, the Ariel Glaser Foundation Against Pediatric AIDS and the National Institute of Health (INS) in Maputo Province. The children were diagnosed and initiated antiretroviral treatment early, in accordance with the national guidelines in force. They were followed up from before treatment initiation and throughout a follow-up period of up to 50 months.
Genetic analysis of mutations associated with resistance to different antiretroviral drugs was conducted at INS in Maputo using next-generation sequencing techniques.
Drug resistance mutations identified in children and mothers
Among the children analysed, almost two-thirds (18 cases, 58.1%) had at least one mutation associated with antiretroviral drug resistance. The most frequent mutations were associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs), a class of drugs used in HIV treatment.
Among the mothers, resistance mutations were detected in half of the cases (five out of 10, 50%). More importantly, shared resistance mutations were identified in three mother-child pairs, corresponding to 30% of the pairs assessed. This finding raises the possibility of the transmission of drug resistance from mother to child and highlights the need to better understand resistance dynamics in the context of mother-to-child HIV transmission.
One of the findings considered particularly relevant by the researchers was the absence of mutations associated with resistance to integrase strand transfer inhibitors (INSTIs), both in children and in mothers. According to the authors, this finding is likely explained by the period during which participants were recruited, between 2018 and 2021, before integrase inhibitor-based treatment regimens became widely used in Mozambique.
The results therefore support Mozambique's transition to dolutegravir-containing regimens, which are now included in the national HIV treatment guidelines.
According to David Torres-Fernandez, the study's first author, “the results show a high prevalence of resistance mutations in both children and mothers, including shared mutations in some pairs. This highlights the importance of improving access to drug resistance testing for children and mothers in order to prevent mortality and poor clinical outcomes.”
Challenges in treatment response and the importance of integrated follow-up
Beyond drug resistance mutations, the study identified important challenges related to clinical outcomes and continuity of treatment.
Of the 79 children followed up, 16 (20.3%) died during the follow-up period. Only 12 of the 47 children with available data (25.5%) achieved sustained virological suppression, meaning they were able to maintain control of the amount of virus in their blood over time. Additionally, 43 children (54.4%) had suboptimal adherence to antiretroviral treatment.
These findings highlight the importance of strengthening clinical follow-up, viral load monitoring and treatment adherence support, even when treatment is initiated early.
For Tacilta Nhampossa, coordinator of CISM's Maternal and Child Health area and one of the study's investigators, the findings demonstrate the need to address antiretroviral drug resistance through an integrated approach that considers both maternal and child health.
“The absence of resistance mutations to integrase inhibitors is an encouraging finding and supports the use of dolutegravir-containing regimens as first-line treatment for children. At the same time, these results highlight the importance of monitoring treatment response, particularly through viral load testing. A child's health cannot be separated from the mother's health and treatment history. An integrated approach is essential, from preventing mother-to-child transmission to the diagnosis, treatment and follow-up of both mother and child over time.”
Contributions to improving HIV treatment
The study highlights the importance of expanding access to antiretroviral drug resistance testing to support better-informed treatment decisions and contribute to improved clinical outcomes, particularly among children living with HIV.
The researchers nevertheless acknowledge some limitations, particularly those related to the sample size and the availability of samples for drug resistance testing. They therefore recommend prospective studies involving larger samples to deepen understanding of resistance patterns and their possible transmission between mothers and children.
The study concludes that the high prevalence of resistance mutations observed in mother-child pairs, combined with the high occurrence of adverse clinical outcomes among children, demonstrates the potential value of making drug resistance testing more accessible to mothers and children in low-income countries.
Reference
Torres-Fernandez D, Fernández-Luis S, Domínguez-Rodríguez S, Nhampossa T, López-Varela E, Lain MG, Naniche D, Vaz P, Ismael N, Spyer MJ, Byott M, Nastouli E, Bassat Q, Rojo P, Rossi P, Giaquinto C, Tagarro A; EPIICAL Consortium. HIV-1 Drug Resistance in Mother-Infant Pairs in Southern Mozambique. Pediatr Infect Dis J. 2026 Sep 28. doi: 10.1097/INF.0000000000005426. Epub ahead of print. PMID: 42802382.
