Dr. Nancy HaigwoodMother-to-child transmission of HIV remains a significant problem in the resource-poor world. Given appropriate prenatal care, and continuation of antiretroviral therapy (ART) for mother and infant during breastfeeding, over 99% of HIV-positive women can expect to deliver a baby free of HIV. But there are still more than 200,000 infected infants born annually to HIV-positive mothers in countries where prenatal care and ART are not readily available. In addition, potentially less toxic interventions, not reliant on strict medication adherence, would clearly be welcomed.
amfAR-funded scientist Dr. Nancy Haigwood and colleagues at Oregon Health and Science University and the National Institutes of Health approached this problem through a monkey model. They examined mother-to-child transmission of a hybrid AIDS virus known as SHIV, which contains elements of both HIV and the simian AIDS virus, SIV. Writing in the April issue of the prominent journal Nature Medicine, Dr. Haigwood and her colleagues reported employing a “passive immunotherapy” strategy based on a cocktail of two potent monoclonal antibodies, isolated from patients with HIV, capable of neutralizing a broad spectrum of AIDS viruses.
One-month-old macaques were orally exposed to SHIV. The monkeys in the experimental group were injected with the antibodies under the skin at 1, 4, 7, and 10 days following exposure. The control monkeys, exposed to the virus but not given the antibodies, were found to have growing virus in their tissues as early as 24 hours following infection (it was previously thought that it takes several days for HIV to take hold in the body.) In contrast, all antibody-treated monkeys were found to be free of virus in their blood and tissues within 2 weeks and throughout a 6-month follow-up period.
From L to R: Philip Barnette, Nancy Haigwood, Jonah Sacha, Bill Sutton, Ann Hessell, Shilpi Pandey, and Tracy Cheever.
The study has important implications. The antibodies could potentially be a less toxic alternative to ART, if they prove to be effective in preventing early HIV infection in humans. This may be particularly important over the long periods of breastfeeding typical of many cultures. ART has a short half-life and requires strict adherence, while antibodies have very much longer periods of activity requiring far fewer doses. Ongoing studies should help define the window of opportunity for effective prevention of HIV transmission after exposure during birth.
But the clear potential for this work to impact cure strategies may be equally exciting. As the study authors note, “early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.” Anything that can affect HIV reservoirs is of strong interest to cure researchers.
Dr. Laurence is amfAR’s senior scientific consultant.