Very early HIV treatment may help babies live medication-free

Initiating antiretroviral therapy (ART) within 48 hours of life for infants born with HIV can lead to sustained viral suppression, as reflected by reduced HIV reservoirs by age 2 years, which suggests the possibility of an ART-free remission.

In an ongoing, phase I/II proof-of-concept study, the estimated probability of maintaining undetectable plasma RNA through age 2 years was 33 percent for infants born to mothers with untreated HIV-1 (cohort 1) and 57 percent for those born to mothers who were receiving pre-emptive triple antiretroviral prophylaxis outside of the study (cohort 2). The infants were started on a three-drug nevirapine-based ART regimen within 48 hours of life, with twice-daily coformulated oral ritonavir 75 mg/m² and lopinavir 300 mg/m² added within 2–4 weeks. [Lancet HIV 2023;doi:10.1016/S2352-3018(23)00236-9]

Among infants who maintained protocol-defined virologic control through week 108, seven of 11 (64 percent) infants in cohort 1 and five of seven (71 percent) in cohort 2 had undetectable HIV-1 DNA. Moreover, 10 of 12 (83 percent) infants in cohort 1 and all seven (100 percent) in cohort 2 tested negative for HIV-1 antibodies.

A total of 10 infants (19 percent), including six in cohort 1 and four in cohort 2, met all criteria for possible analytical treatment interruption.

As for safety, reversible grade 3 or 4 adverse events were documented in 44 percent of infants in cohort 1 and 35 percent of those in cohort 2.

“Moving away from reliance on daily ART to control HIV would be a huge improvement to the quality of life of these children,” said senior study author Dr Ellen Chadwick of Northwestern University Feinberg School of Medicine in Chicago, Illinois, US.

The proof-of-concept study serves to replicate the case of HIV remission seen in the “Mississippi baby,” who began ART at 30 hours of life, received treatment for 18 months, and achieved 27 months of ART-free remission before the virus rebounded. [J Int AIDS Soc 2014;17:19859]

The study was conducted in 11 countries (Brazil, Haiti, Kenya, Malawi, South Africa, Tanzania, Thailand, Uganda, US, Zambia, and Zimbabwe) and included 54 infants (61 percent girls), including 34 in cohort 1 and 20 in cohort 2, with confirmed in-utero HIV-1.

“With earlier treatment, we hope to limit or prevent the establishment of viral reservoirs in the body. These viral reservoirs hold small amounts of hidden virus which are hard to reach with ART. By shrinking these reservoirs, we expect to increase the amount of time that patients can be in remission, without needing daily ART,” explained study co-author Dr Jennifer Jao of Northwestern University Feinberg School of Medicine in Chicago, Illinois, US.

Additionally, smaller viral reservoirs may allow the use of newer treatments such as long-acting antibody therapies or therapeutic vaccines instead of daily ART, as Chadwick pointed out.

“Our results show a higher percentage of children might be eligible to interrupt therapy than we expected, and the next step is to stop ART and see how many children actually achieve remission. If even one child achieves remission, that would be considered a success,” said Chadwick.

“Today, newer more effective and better tolerated HIV medications are available for infants than when the study began, strengthening the prospect of limiting viral reservoirs and testing for possible remission in infants and children with HIV. Overall, this is an exciting advancement and an opportunity to change the course of paediatric HIV infection,” she added.