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Johannesburg, South Africa

Hong H.A.,University of Witwatersrand | Paximadis M.,University of Witwatersrand | Gray G.E.,Perinatal HIV Research Unit | Kuhn L.,Columbia University | Tiemessen C.T.,University of Witwatersrand
Clinical Immunology

KIR2DS4 is the only activating gene within the A haplotype, and alleles of KIR2DS4 can encode either functional (KIR2DS4-f) or non-functional (KIR2DS4-v) variants. To establish the role of KIR2DS4 in the context of HIV-1 mother-to-child transmission, we KIR genotyped 145 HIV-1 non-transmitting mothers (NT) and their exposed uninfected infants (EU), and 72 HIV-1 transmitting mothers (TR) and their infected infants [intrapartum (IP), in utero (IU) or IU2 (an IU-enriched infected group)]. The frequency of KIR2DS4-v was significantly higher in IU2 infants compared to EU infants (P= 0.022, OR. = 2.88); this association was more significant amongst AA haplotypes (P= 0.004, OR. = 18.4). Possession of KIR2DS4-f in the mother with absence in the infant (M+I. - discordance) was associated with a higher risk of IP transmission (P= 0.005, OR. = 3.84); whilst in M. - I. + discordance, infant possession of KIR2DS4-v was associated with increased risk of IU acquisition (P= 0.002; OR. = 6.40). This study highlights the importance of KIR2DS4 in HIV-1 transmission/acquisition. © 2013 Elsevier Inc. Source

Egger M.,University of Bern | Spycher B.D.,University of Bern | Sidle J.,Moi University | Weigel R.,Lighthouse Trust | And 10 more authors.
PLoS Medicine

Background: The World Health Organization estimates that in sub-Saharan Africa about 4 million HIV-infected patients had started antiretroviral therapy (ART) by the end of 2008. Loss of patients to follow-up and care is an important problem for treatment programmes in this region. As mortality is high in these patients compared to patients remaining in care, ART programmes with high rates of loss to follow-up may substantially underestimate mortality of all patients starting ART. Methods and Findings: We developed a nomogram to correct mortality estimates for loss to follow-up, based on the fact that mortality of all patients starting ART in a treatment programme is a weighted average of mortality among patients lost to follow-up and patients remaining in care. The nomogram gives a correction factor based on the percentage of patients lost to follow-up at a given point in time, and the estimated ratio of mortality between patients lost and not lost to follow-up. The mortality observed among patients retained in care is then multiplied by the correction factor to obtain an estimate of programme-level mortality that takes all deaths into account. A web calculator directly calculates the corrected, programme-level mortality with 95% confidence intervals (CIs). We applied the method to 11 ART programmes in sub-Saharan Africa. Patients retained in care had a mortality at 1 year of 1.4% to 12.0%; loss to follow-up ranged from 2.8% to 28.7%; and the correction factor from 1.2 to 8.0. The absolute difference between uncorrected and corrected mortality at 1 year ranged from 1.6% to 9.8%, and was above 5% in four programmes. The largest difference in mortality was in a programme with 28.7% of patients lost to follow-up at 1 year. Conclusions: The amount of bias in mortality estimates can be large in ART programmes with substantial loss to follow-up. Programmes should routinely report mortality among patients retained in care and the proportion of patients lost. A simple nomogram can then be used to estimate mortality among all patients who started ART, for a range of plausible mortality rates among patients lost to follow-up. © 2011 Egger et al. Source

Hoffmann C.J.,Johns Hopkins University | Chaisson R.E.,Johns Hopkins University | Martinson N.A.,Johns Hopkins University | Martinson N.A.,Perinatal HIV Research Unit

Objectives: Many randomized and cohort studies have reported a survival benefit with cotrimoxazole prophylaxis without detecting a difference in tuberculosis (TB) incidence by cotrimoxazole status. However, several in vitro studies have reported that cotrimoxazole possesses anti-TB activity. We sought to compare TB incidence and TB diagnostic yield by cotrimoxazole use among participants in a well characterized cohort of HIV-infected adults living in a high TB prevalence region. Methods: We analyzed prospective data from a long-term longitudinal cohort of adults receiving HIV care and TB investigations in Soweto, South Africa. Using longitudinal analysis, we compared total and laboratory confirmed TB incidence by cotrimoxazole status as well as all-cause mortality. In addition, we compared TB culture results by cotrimoxazole status. Results: In a multivariable analysis, adjusted for sex, body mass index, WHO clinical stage, time-updated CD4 count, and antiretroviral therapy status, we observed an association between cotrimoxazole and an increase in TB incidence (hazard ratio 1.7, 95% CI: 1.2, 2.2). However, when restricted to laboratory-confirmed TB, there was no association between cotrimoxazole and TB incidence (hazard ratio: 0.97, 95% CI: 0.39, 2.4). In TB cases, we found no difference in the proportion of positive sputum cultures or days to culture positivity by cotrimoxazole status. Cotrimoxazole was associated with a reduction in mortality. Conclusions: In this cohort with a mortality benefit from cotrimoxazole, we found an increased risk of all TB among individuals using cotrimoxazole, likely a result of residual confounding, but no association between use of cotrimoxazole and laboratory-confirmed TB. Cotrimoxazole did not compromise TB diagnosis. © 2014 Hoffmann et al. Source

Van Rooyen H.,STIs and TB Unit | Van Rooyen H.,Human science Research Council | McGrath N.,London School of Hygiene and Tropical Medicine | McGrath N.,University of South Africa | And 7 more authors.
AIDS and Behavior

Mounting evidence exists that mobile voluntary counselling and testing (VCT) is able to extend coverage to new localities and populations. We describe two feasibility and acceptability pilot studies conducted in rural and urban South Africa in preparation for the larger NIMH Project Accept HIV prevention trial. A total of 1,015 individuals participated in the pilot studies. Participants in rural Vulindlela were younger (median 22 years) compared to urban Soweto (p < 0.001). Young people were more likely to be first time testers in both sites (p = 0.01 in Vulindlela, p < 0.001 in Soweto), with significantly more men likely to be first time testers than women (p = 0.01 in Vulindlela, p < 0.001 in Soweto). User satisfaction with mobile VCT was extremely high in both sites. Our study shows that providing mobile, high-quality and easy to access services in a high prevalence context is a feasible way to engage youth, men and more rural populations in HIV counselling and testing. © 2012 Springer Science+Business Media New York. Source

Tiemessen C.T.,South African National Institute for Communicable Diseases | Shalekoff S.,South African National Institute for Communicable Diseases | Meddows-Taylor S.,South African National Institute for Communicable Diseases | Schramm D.B.,South African National Institute for Communicable Diseases | And 5 more authors.
Journal of Infectious Diseases

Human immunodeficiency virus (HIV)-specific natural killer (CD3- cells), CD4, and CD8 T cellular responses were determined in 79 HIV-1-infected women in response to HIV-1 peptide pools (Gag, Pol, Nef, Reg, and Env) with use of a whole-blood intracellular cytokine staining assay that measures interferon-γ and/or interleukin-2. HIV-specific CD3- cell responses to any region (Env and Reg predominantly targeted) were associated with lower viral load (P = .031) and higher CD4 T cell count (P = .015). Env-specific CD3- cell responses were stronger in women who had both Gag CD4 and CD8 T cell responses and, in turn, was associated with lower viral load (P = .005). CD3- cell responders had significantly higher representation of CD4 T cell responses to Env and Reg (P = .012 and P = .015, respectively) and higher magnitudes of CD4 T cell responses (P = .017 and P = .037, respectively) than did nonresponders. Peptide-specific natural killer cells are associated with markers of less severe disease progression among HIV-1-infected women (lower viral load and higher CD4 T cell count) and with stronger HIV-specific T cell responses. © 2010 by the Infectious Diseases Society of America. All rights reserved. Source

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