Editor’s note:
Currently, the choice of second-line antiretroviral therapy (ART) for children infected with HIV is extremely limited. At the recently concluded 12th International AIDS Society HIV Science Conference (IAS 2023), researchers announced the results of a significant clinical study, the CHAPAS-4 (Conference Abstract No.: OALBB0503), focusing on the long-term treatment outcomes of second-line therapy in children with HIV infections. We specially invited Professor Wang Hui from National Clinical Research Center for Infectious Diseases, The Third People’s of Shenzhen and The Second Affilliated Hospital of Southern University of Science and Technology, China to provide a brilliant review of this research.Research Content:
In this 2×4 factorial trial, children with HIV from Uganda, Zambia, and Zimbabwe were randomized to receive second-line tenofovir alafenamide/emtricitabine (TAF/FTC) or standard of care (SOC) backbone drugs, abacavir (ABC) or zidovudine (AZT) combined with lamivudine (3TC) (randomization 1), and one of four core drugs: dolutegravir (DTG) or ritonavir-boosted darunavir (DRV/r), atazanavir (ATV/r) or lopinavir (LPV/r) (randomization 2). The primary endpoint was a viral load (VL) of <400 copies/mL at week 96, analyzed using logistic regression based on intention-to-treat.
Research Results:
The study enrolled 919 children aged 3-15 years, 54% male, with a median viral load of 17,573 copies/mL and CD4 positive cell count of 669 cells/mL. All participants switched from an NNRTI-based ART regimen to a different second-line treatment group. At week 96, the proportion of VL<400 copies/mL in the TAF/FTC group was 89.4% (406/454), statistically indistinguishable from 83.3% (378/454) in the SOC group. In the second randomization treatments, the percentages were 92.0% (208/226) for the DTG group, 88.3% (203/230) for the DRV/r group, 84.3% (193/229) for the ATV/r group, and 80.7% (180/223) for the LPV/r group. Analysis indicated the TAF/FTC group outperformed the SOC group, the DTG group surpassed both the LPV/r and ATV/r groups, and the DRV/r group tended to perform better than both the LPV/r and ATV/r groups. The ATV/r group’s efficacy was not inferior to the LPV/r group (see Table 1). Table 1. Comparison of VL at 96 weeks across antiretroviral treatment groups.
By week 144, the proportions of VL<60 copies/mL and VL<1000 copies/mL were similar to those at week 48. All groups showed improvements in CD4 counts. In terms of safety, the ATV/r group experienced more grade 3/4 adverse events (AEs), primarily characterized by hyperbilirubinemia (P<0.0001) than the LPV/r group. The DTG group had fewer AEs compared to the LPV/r group (P=0.02). There was no evidence that treatment regimens containing DTG±TAF led to excessive weight gain in children. The growth parameters of children in the TAF group were significantly improved compared to the SOC group. Kidney and bone health statuses were similar across the DTG, DRV/r, ATV/r, and LPV/r groups. During the study, one child died, which was unrelated to the treatment, and only 3% of children experienced serious adverse events.
Research Conclusion:
Treatment regimens containing TAF/FTC and DTG performed virologically better than regimens with SOC backbone drugs and boosted PIs (ATV/r, LPV/r), and they exhibited good safety profiles. The results of this study suggest that antiretroviral treatment combinations of TAF/FTC (±DTG or boosted DRV or ATV) are very beneficial for children with HIV, and these drugs will increase the chances of these children accessing safe and effective second-line ART medications.
Expert Review:
AIDS is a contagious disease caused by the human immunodeficiency virus (HIV), mainly spread through sexual contact, blood, and mother-to-child transmission. Children infected with HIV can face various health issues, including growth delays, malnutrition, and opportunistic infections. Therefore, timely and effective antiretroviral treatment is crucial for these children. Although significant progress has been made in the antiretroviral treatment of children with HIV in recent years, there are still pressing issues to address. In many countries, a significant portion of children with HIV still cannot access timely antiretroviral treatments, leading to worsening conditions and increased risks of complications. On the other hand, genetic variations and disease progression in different children can result in varying drug responses. Tailoring treatments according to each child’s specific situation is essential, but the drug choices for treating children with HIV are limited. Deciding on medications that do not compromise the efficacy and safety of antiretroviral treatments based on the physiological characteristics and metabolic differences of children is paramount. Many countries have yet to establish antiretroviral treatment regimens and monitoring systems specifically for children, posing challenges to clinical practice. This clinical study, addressing current challenges in the antiretroviral treatment of children with HIV, compared the efficacy and safety of multiple antiretroviral treatments over 96 weeks. The proposed TAF/FTC, DTG, or boosted PI options could serve as alternatives for second-line antiretroviral treatments for children with HIV. This offers a solution to the problem of suboptimal results or severe side effects from the first-line regimen, holding significant clinical guidance value. In conclusion, children with HIV require long-term antiretroviral treatments and lifestyle guidance to reduce morbidity and mortality. However, many countries and regions lack the medical resources and professionals to support this demand. Antiretroviral treatments for children with HIV continue to face challenges. We hope that medical institutions and research institutes will work together to strengthen policy-making, technological innovation, and resource investment, jointly improving the prognosis and survival of children with HIV.
Reference:
V. Musiime, A.J. Szubert, M. Bwakura Dangarembizi, et al. Increasing second-line antiretroviral therapy options for children with HIV in Africa: week-96 efficacy and safety results of the CHAPAS-4 randomized trial. IAS 2023 Abstract OALBB0503.
Professor Wang Hui
Director of the AIDS Medical Center, Affiliated Second Hospital of Southern University of Science and Technology (Shenzhen Third People’s Hospital)
