Center for Global Health and Development Papers

P02-07. High Concentrations of Interleukin-15 and Low Concentrations of CCL5 in Breast Milk are Associated with Protection against Postnatal HIV Transmission

Thu, 22 Oct 2009 00:00:00 GMT

P02-07. High Concentrations of Interleukin-15 and Low Concentrations of CCL5 in Breast Milk are Associated with Protection against Postnatal HIV Transmission Walter, J; Ghosh, MK; Kuhn, L; Semrau, K; Sinkala, M; Kankasa, C; Thea, DM; Aldrovandi, GM

Restriction of HIV-1 Genotypes in Breast Milk Does Not Account for the Population Transmission Genetic Bottleneck That Occurs following Transmission

Tue, 20 Apr 2010 00:00:00 GMT

Restriction of HIV-1 Genotypes in Breast Milk Does Not Account for the Population Transmission Genetic Bottleneck That Occurs following Transmission Heath, Laura; Conway, Susan; Jones, Laura; Semrau, Katherine; Nakamura, Kyle; Walter, Jan; Decker, W. Don; Hong, Jason; Chen, Thomas; Heil, Marintha; Sinkala, Moses; Kankasa, Chipepo; Thea, Donald M.; Kuhn, Louise; Mullins, James I.; Aldrovandi, Grace M. BACKGROUND. Breast milk transmission of HIV-1 remains a major route of pediatric infection. Defining the characteristics of viral variants to which breastfeeding infants are exposed is important for understanding the genetic bottleneck that occurs in the majority of mother-to-child transmissions. The blood-milk epithelial barrier markedly restricts the quantity of HIV-1 in breast milk, even in the absence of antiretroviral drugs. The basis of this restriction and the genetic relationship between breast milk and blood variants are not well established. METHODOLOGY/PRINCIPAL FINDINGS. We compared 356 HIV-1 subtype C gp160 envelope (env) gene sequences from the plasma and breast milk of 13 breastfeeding women. A trend towards lower viral population diversity and divergence in breast milk was observed, potentially indicative of clonal expansion within the breast. No differences in potential N-linked glycosylation site numbers or in gp160 variable loop amino acid lengths were identified. Genetic compartmentalization was evident in only one out of six subjects in whom contemporaneously obtained samples were studied. However, in samples that were collected 10 or more days apart, six of seven subjects were classified as having compartmentalized viral populations, highlighting the necessity of contemporaneous sampling for genetic compartmentalization studies. We found evidence of CXCR4 co-receptor using viruses in breast milk and blood in nine out of the thirteen subjects, but no evidence of preferential localization of these variants in either tissue. CONCLUSIONS/SIGNIFICANCE. Despite marked restriction of HIV-1 quantities in milk, our data indicate intermixing of virus between blood and breast milk. Thus, we found no evidence that a restriction in viral genotype diversity in breast milk accounts for the genetic bottleneck observed following transmission. In addition, our results highlight the rapidity of HIV-1 env evolution and the importance of sample timing in analyses of gene flow.

Economic Outcomes of Patients Receiving Antiretroviral Therapy for HIV/AIDS in South Africa Are Sustained through Three Years on Treatment

Tue, 14 Sep 2010 00:00:00 GMT

Economic Outcomes of Patients Receiving Antiretroviral Therapy for HIV/AIDS in South Africa Are Sustained through Three Years on Treatment Rosen, Sydney; Larson, Bruce; Brennan, Alana; Long, Lawrence; Fox, Matthew; Mongwenyana, Constance; Ketlhapile, Mpefe; Sanne, Ian BACKGROUND. Although the medical outcomes of antiretroviral therapy (ART) for HIV/AIDS are well described, less is known about how ART affects patients' economic activities and quality of life, especially after the first year on ART. We assessed symptom prevalence, general health, ability to perform normal activities, and employment status among adult antiretroviral therapy patients in South Africa over three full years following ART initiation. METHODOLOGY/PRINCIPAL FINDINGS. A cohort of 855 adult pre-ART patients and patients on ART for <6 months was enrolled and interviewed an average of 4.4 times each during routine clinic visits for up to three years after treatment initiation using an instrument designed for the study. The probability of pain in the previous week fell from 74% before ART initiation to 32% after three years on ART, fatigue from 66% to 12%, nausea from 28% to 4%, and skin problems from 55% to 10%. The probability of not feeling well physically yesterday fell from 46% to 23%. Before starting ART, 39% of subjects reported not being able to perform their normal activities sometime during the previous week; after three years, this proportion fell to 10%. Employment rose from 27% to 42% of the cohort. Improvement in all outcomes was sustained over 3 years and for some outcomes increased in the second and third year. CONCLUSIONS/SIGNIFICANCE. Improvements in adult ART patients' symptom prevalence, general health, ability to perform normal activities, and employment status were large and were sustained through the first three years on treatment. These results suggest that some of the positive economic and social externalities anticipated as a result of large-scale treatment provision, such as increases in workforce participation and productivity and the ability of patients to carry on normal lives, may indeed be accruing.

The Global Health System: Lessons for a Stronger Institutional Framework

Tue, 26 Jan 2010 00:00:00 GMT

The Global Health System: Lessons for a Stronger Institutional Framework Moon, Suerie; Szlezák, Nicole A.; Michaud, Catherine M.; Jamison, Dean T.; Keusch, Gerald T.; Clark, William C.; Bloom, Barry R. In the last in a series of four articles highlighting the changing nature of global health institutions, Suerie Moon and colleagues propose future actions to strengthen these institutions.