Education:
BA 1979 Political Science - McGill University, Montreal
BSc 1981 Physiology - McGill University, Montreal
MD CM 1985 Medicine - McGill University, Montreal
Postdoctoral Research Fellowship:
1989-1992 Harbor-UCLA Medical Center
Started at USC: 2003
Research Topics: Immunology, Virology
Research Description
Our laboratory has a broad-based program to investigate the transmission of HIV from mother to child and the pathogenesis of HIV in children. Last year according to the World Health Organization, 2,000 children a day became infected with HIV. Most of these children live in sub-Saharan Africa where most children are becoming infected through breast milk. Alternatives to breast-feeding in these countries are unaffordable, unsafe, and culturally unacceptable. We are involved in a large clinical trial in Africa and are using specimens collected from this well-characterized cohort to elucidate virologic and immunologic factors modulating transmission risk. Chronic HIV infection is associated with a complex, heterogeneous population of HIV variants. In contrast, a newly infected individual is usually infected with a single or a few variants. Although this transmission “bottleneck” was recognized over a decade ago, the biologic basis for this phenomenon has yet to be elucidated. Is this selection the result of an inefficient stochastic transmission event, or are these viruses selected for because of their replicative advantage in the transmitting compartment (genital secretions, breast milk, blood) and/or within the new host? We are characterizing the genotypic and functional characteristics of HIV strains transmitted via various routes. Since these early variants are the targets of preventative efforts, understanding their distinguishing features is central to vaccine development. We are also performing comprehensive virologic studies the effects of inflammation HIV evolution and transmissibility.
We have already established that breast milk is a distinct immunologic compartment. We are currently using state-of-the-art techniques to compare the cellular and humoral responses in blood and mucosal compartments and to determine their influence on transmission. These studies will help elucidate key to designing sustainable interventions to prevent mother-to-child transmission of HIV.
Selected Publications
Kuhn L, Aldrovandi GM, Sinkala M, Kankasa C, Semrau K, Mwiya M, Kasonde P, Scott N, Vwalika C, Walter J, Bulterys M, Tsai WY, Thea DM. - Effects of Early, Abrupt Weaning for HIV-free Survival of Children in Zambia. - N Engl J Med [ 2008 ] Jun 4; . PubMed
Semrau K, Ghosh M, Kankasa C, Sinkala M, Kasonde P, Mwiya M, Thea DM, Kuhn L, Aldrovandi GM. - Temporal and lateral dynamics of HIV shedding and elevated sodium in breast milk among HIV-positive mothers during the first 4 months of breast-feeding. - J Acquir Immune Defic Syndr [ 2008 ] Mar 1;47(3):320-8 . PubMed
Fox MP, Brooks D, Kuhn L, Aldrovandi G, Sinkala M, Kankasa C, Mwiya M, Horsburgh R, Thea DM. - Reduced mortality associated with breast-feeding-acquired HIV infection and breast-feeding among HIV-infected children in Zambia. - J Acquir Immune Defic Syndr [ 2008 ] May 1;48(1):90-6 . PubMed
Kuhn L, Sinkala M, Kankasa C, Semrau K, Kasonde P, Scott N, Mwiya M, Vwalika C, Walter J, Tsai WY, Aldrovandi GM, Thea DM. - High uptake of exclusive breastfeeding and reduced early post-natal HIV transmission. - PLoS ONE [ 2007 ] Dec 26;2(12):e1363 . PubMed
Kuhn L, Thea DM, Aldrovandi GM. - Bystander effects: children who escape infection but not harm. - J Acquir Immune Defic Syndr [ 2007 ] Dec 15;46(5):517-8 . PubMed
Chi BH, Sinkala M, Mbewe F, Cantrell RA, Kruse G, Chintu N, Aldrovandi GM, Stringer EM, Kankasa C, Safrit JT, Stringer JS. - Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trial. - Lancet [ 2007 ] Nov 17;370(9600):1698-705 . PubMed
Castelletti E, Lo Caputo S, Kuhn L, Borelli M, Gajardo J, Sinkala M, Trabattoni D, Kankasa C, Lauri E, Clivio A, Piacentini L, Bray DH, Aldrovandi GM, Thea DM, Veas F, Nebuloni M, Mazzotta F, Clerici M. - The mucosae-associated epithelial chemokine (MEC/CCL28) modulates immunity in HIV infection. - PLoS ONE [ 2007 ] Oct 3;2(10):e969 . PubMed
Dorosko SM, Thea DM, Saperstein G, Russell RM, Paape MJ, Hinckley LS, Decker WD, Semrau K, Sinkala M, Kasonde P, Kankasa C, Aldrovandi GM, Hamer DH. - Veterinary field test as screening tool for mastitis and HIV-1 viral load in breastmilk from HIV-infected Zambian women. - Breastfeed Med [ 2007 ] Sep;2(3):172-5 . PubMed
Walter J, Kuhn L, Ghosh MK, Kankasa C, Semrau K, Sinkala M, Mwiya M, Thea DM, Aldrovandi GM. - Low and undetectable breast milk interleukin-7 concentrations are associated with reduced risk of postnatal HIV transmission. - J Acquir Immune Defic Syndr [ 2007 ] Oct 1;46(2):200-7 . PubMed
Bennetto-Hood C, Aldrovandi GM, King JR, Woodman K, Ashouri N, Acosta EP. - Persistence of nevirapine in breast milk after discontinuation of treatment. - Clin Infect Dis [ 2007 ] Aug 1;45(3):391-4 . PubMed
