Makerere University

About: Makerere University is a education organization based out in Kampala, Uganda. It is known for research contribution in the topics: Population & Acquired immunodeficiency syndrome (AIDS). The organization has 7220 authors who have published 12405 publications receiving 366520 citations. The organization is also known as: Makerere University Kampala & MUK.

Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1-Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda.

Abstract: Background Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings. Methods and Findings Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7–6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0–0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP. Conclusions Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of 5% per year.

Intimate partner violence is associated with incident Hiv infection in women in Uganda

Abstract: OBJECTIVES: To quantify the association between intimate partner violence (IPV) and incident HIV infection in women in the Rakai Community Cohort Study between 2000 and 2009. DESIGN AND METHODS: Data were from the Rakai Community Cohort Study annual surveys between 2000 and 2009. Longitudinal data analysis was used to estimate the adjusted incidence rate ratio (IRR) of incident HIV associated with IPV in sexually active women aged 15-49 years, using a multivariable Poisson regression model with random effects. The population attributable fraction was calculated. Putative mediators were assessed using Baron and Kenny's criteria and the Sobel-Goodman test. RESULTS: Women who had ever experienced IPV had an adjusted IRR of incident HIV infection of 1.55 (95% CI 1.25-1.94, P = 0.000), compared with women who had never experienced IPV. Risk of HIV infection tended to be greater for longer duration of IPV exposure and for women exposed to more severe and more frequent IPV. The adjusted population attributable fraction of incident HIV attributable to IPV was 22.2% (95% CI 12.5-30.4). There was no evidence that either condom use or number of sex partners in the past year mediated the relationship between IPV and HIV. CONCLUSION: IPV is associated with incident HIV infection in a population-based cohort in Uganda, although the adjusted population attributable fraction is modest. The prevention of IPV should be a public health priority, and could contribute to HIV prevention. Language: en

Treatment of hepatocellular carcinoma with adriamycin. Preliminary communication.

Abstract: In a Phase II clinical trial, 14 patients with histologically proven primary hepatocellular carcinoma were treated with adriamycin administered intravenously at a dose of 75 mg/m2 every 3 weeks All 11 evaluable patients responded with 3 exhibiting complete tumor regression after two, three, and five courses of adriamycin respectively The remission durations for these 3 were 3, 6, and 7 months, and their survivals were 8, 9, and 13 months, respectively The median survival of the evaluable patients is 8 months (range 1-13 months) The side effects encountered included myelosuppression, anorexia, nausea, vomiting, and alopecia Adriamycin seems to be an effective agent in hepatocellular carcinoma Further trials are underway to test its true efficacy both singly and in combination with other drugs in the management of this tumor

Global phylogeography and ancient evolution of the widespread human gut virus crAssphage

Abstract: Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome.

Polymorphisms in the Plasmodium falciparum pfcrt and pfmdr-1 Genes and Clinical Response to Chloroquine in Kampala, Uganda

Abstract: The molecular mechanism of chloroquine resistance in Plasmodium falciparum remains uncertain. Polymorphisms in the pfcrt and pfmdr-1 genes have been associated with chloroquine resistance in vitro, although field studies are limited. In evaluations of known polymorphisms in parasites from patients with uncomplicated malaria in Kampala, Uganda, the presence of 8 pfcrt mutations and 2 pfmdr-1 mutations did not correlate with clinical response to therapy with chloroquine. Most notably, the pfcrt lysinerthreonine mutation at position 76, which recently correlated fully with chloroquine resistance in vitro, was present in 100% of 114 isolates, of which about half were from patients who recovered clinically after chloroquine therapy. These results suggest that, although key pfcrt polymorphisms may be necessary for the elaboration of resistance to chloroquine in areas with high levels of chloroquine resistance, other factors, such as host immunity, may contribute to clinical outcomes. Resistance of the malaria parasite Plasmodium falciparum to commonly used antimalarial agents is a large and growing problem. In particular, resistance to chloroquine, which remains the standard therapy for malaria in most of Africa, is an urgent concern [1]. The molecular basis of chloroquine resistance remains uncertain. Chloroquine resistance has been correlated with mutations in a number of P. falciparum genes, although some results have been inconsistent [2]. In initial studies of the P. falciparum multidrug resistance gene (pfmdr-1), an AsnrTyr mutation at amino acid 86 (N86Y) and other mutations in this gene correlated with chloroquine resistance [3]. However, in several field studies, associations between pfmdr-1 point mutations and in vivo or in vitro chloroquine resistance were not consistent [2]. More recently, transfection studies showed that the replacement of mutant pfmdr-1 with the wild-type sequence in resistant parasites decreased chloroquine resistance from high to moderate levels [4]. Thus, it appears that, although mutations