Early ART Is Safe, Key to Suppressing HIV to Undetectable Levels in Infants

Recent research published in The Lancet HIV further contributed to evidence that giving antiretroviral therapy (ART) to newborns with HIV within the first days of life, instead of within weeks or months, can safely suppress HIV in the blood to undetectable levels. ART can help control the virus, preventing it from progressing to AIDS.

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According to the authors, an individual living with HIV who is not receiving ART has a 15% to 45% chance of transmitting HIV during pregnancy, childbirth, or breast-feeding. This chance decreases to less than 1% if women with HIV receive ART during pregnancy.

“We sought proof of the concept that if you can safely treat babies with a 3-drug regimen within 48 hours of life, you can limit the buildup of these reservoirs and get them to very low levels that may lead to ART-free remission, where the virus doesn’t come back quickly if the ART is stopped in later phases of the trial,” said study co-leader Deborah Persaud, MD, physician-scientist and research at Johns Hopkins Children’s Center, in the press release.

Standard treatment of babies with HIV typically starts at 2 to 3 months of age, according to the authors. This often is due to delays in testing and receiving results, especially outside of the United States where the burden of HIV is highest and ART drugs aren’t as accessible. In addition, the adverse effects of ART—anemia, nausea, vomiting, and diarrhea—are a concern for some patients.

To stop the formation of hard-to-treat viral reservoirs, the authors sought to replicate what is believed to be the first documented case of HIV remission in a child born with HIV and started infants on treatment within the first 48 hours after birth. The reservoirs consist of cells that carry genetic material of latent viruses and antiviral drugs are unable to reach them, causing HIV to survive in the body.

“If you treat at 2 to 3 months of age, when most children start a regimen, very, very, very few kids would actually get to this undetectable stage by 2 years of age,” said Persaud in the press release. “It would actually take them until 5 years of age and older to get to a low HIV DNA level, and it’s never to this undetectable level.”

A total of 54 newborns were enrolled in the study and placed in 2 groups. One group of 34 infants whose mothers were not on ART during pregnancy were started on a 3-drug oral ART regimen that consisted of azidothymidine (Retrovir; Wellcome PLC) or abacavir (Ziagen; ViiV Healthcare), lamivudine (Epivir; ViiV Healthcare Company), and nevirapine (Viramune; Boehringer Ingelheim) within 2 days of life. Previously, the drugs had shown to help prevent HIV transfer to newborns. The second group of 20 infants whose mothers had HIV and were on ART during pregnancy were started on the same 3-drug regimen; however, a lower dose of nevirapine was introduced shortly after birth. In addition, infants in this group were switched to the same study regimen as the first group by 10 days of age.

A fourth medicine, lopinavir-ritonavir, was added to the regimen for all enrolled infants who were HIV positive after reaching 14 days of age. Further, both groups remained on ART through the infants’ first 2 years of life.

The results indicated that infants in group 1 and group 2 had a 33% and 57% chance, respectively, of reaching and maintaining undetectable plasma levels of HIV in the blood beyond 2 years of age. In addition, among the participants who remained with virologic suppression, 83% in group 1 and 100% in group 2 tested negative for HIV antibodies, and 64% in group 1 and 71% in group 2 had no detectable HIV DNA. Approximately 19% of all enrolled infants met the study’s criteria for becoming eligible to stop treatment in later phases of the trial.

The results indicate that early ART is safe and is key to suppressing HIV to undetectable levels during early childhood periods of rapid growth. Further, this very early treatment strategy can be a first step toward getting more infants in remission, allowing them to remain off antiretroviral drugs for longer periods, according to the authors. Persaud also explains that, when grown up, the children will not need to face the stigma of taking daily HIV medicine.

“Overall, these 4 drugs are not the most potent ART regimen, but they were the only drugs approved for the prevention of HIV in newborns and treatment of infants, at the time of the study,” said Persaud in the press release.

Reference

Johns Hopkins Medicine. Study affirms benefit of very early antiretroviral therapy within hours of birth for newborns with HIV. News release. December 5, 2023. Accessed December 7, 2023. https://www.eurekalert.org/news-releases/1010127