Combination antiretroviral treatment (ART) initiated shortly after HIV infection may prevent seeding of a long-lasting reservoir of latently infected cells in some infants. We propose an interventional study in Botswana to screen for HIV infection from birth and provide immediate ART to infected infants. At 24 months from ART initiation, infants without viral reservoir detection will undergo a controlled treatment interrupton with close evaluation for viral rebound. We will enroll 50 HIV+ infants into two parallel early treatment cohorts: 30 infants who test HIV+ within 72 hours of birth and initiate ART at < 7 days of life, and 20 infants who test HIV- within 72 hours of birth but HIV+ within 42 days of life and initiate ART by 56 days of life. Primary study aims will evaluate safety and efficacy of early ART; virologic and immunologic outcomes with early ART; and the possibility of functional cure (or the dynamics of viral rebound) after ART interruption. In Botswana, an established research infrastructure allows rapid diagnosis of HIV infection and high rates of treatment adherence and follow-up. In Boston, specialized virologic and immunologic testing is available to study viral reservoirs and the immunologic impact of early treatment. This unique collaboration will allow for a detailed investigation of how cellular HIV reservoirs, immune responses, and mechanisms of viral long-term persistence can be manipulated through early ART initiation.
The recent description of an infant with functional cure of HIV infection after starting antiretroviral therapy (ART) in the first days of life raises the questionof whether early ART can prevent the seeding of a long-lasting reservoir of latently infected cells in some infants. We propose an interventional study in Botswana to replicate these conditions and study the virologic and immunologic outcomes. At 24 months, infants without viral reservoir detection will undergo a controlled treatment interruption to determine if this strategy can lead t functional cure of HIV infection.
| Kuo, Hsiao-Hsuan; Ahmad, Rushdy; Lee, Guinevere Q et al. (2018) Anti-apoptotic Protein BIRC5 Maintains Survival of HIV-1-Infected CD4+ T Cells. Immunity 48:1183-1194.e5 |
| Ibrahim, Maryanne; Moyo, Sikhulile; Mohammed, Terence et al. (2017) Brief Report: High Sensitivity and Specificity of the Cepheid Xpert HIV-1 Qualitative Point-of-Care Test Among Newborns in Botswana. J Acquir Immune Defic Syndr 75:e128-e131 |
| Gattinoni, Luca; Speiser, Daniel E; Lichterfeld, Mathias et al. (2017) T memory stem cells in health and disease. Nat Med 23:18-27 |
| Lee, Guinevere Q; Orlova-Fink, Nina; Einkauf, Kevin et al. (2017) Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells. J Clin Invest 127:2689-2696 |
| Orlova-Fink, Nina; Chowdhury, Fatema Z; Sun, Xiaoming et al. (2017) Preferential susceptibility of Th9 and Th2 CD4+ T cells to X4-tropic HIV-1 infection. AIDS 31:2211-2215 |
| Lee, Guinevere Q; Lichterfeld, Mathias (2016) Diversity of HIV-1 reservoirs in CD4+ T-cell subpopulations. Curr Opin HIV AIDS 11:383-7 |
| Kuritzkes, Daniel R (2016) Hematopoietic stem cell transplantation for HIV cure. J Clin Invest 126:432-7 |
| Paiardini, Mirko; Lichterfeld, Mathias (2016) Follicular T helper cells: hotspots for HIV-1 persistence. Nat Med 22:711-2 |
