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      An assessment of fishing communities around Lake Victoria, Uganda, as potential populations for future HIV vaccine efficacy studies: an observational cohort study

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          Abstract

          Background

          An effective HIV vaccine is still elusive. Of the 9 HIV preventive vaccine efficacy trials conducted to-date, only one reported positive results of modest efficacy. More efficacy trials need to be conducted before one or more vaccines are eventually licensed. We assessed the suitability of fishing communities in Uganda for future HIV vaccine efficacy trials.

          Methods

          A community-based cohort study was conducted among a random sample of 2191 participants aged 18–49 years. Data were collected on socio-demographic characteristics, HIV risky behaviors, and willingness to participate in future HIV vaccine trials (WTP). Venous blood was collected for HIV serological testing. Retention/follow rates and HIV incidence rates per 100 person years at-risk (pyar) were estimated. Adjusted prevalence proportion ratios (PPRs) of retention and odds ratios (ORs) of lack of WTP were estimated using log-binomial and logistic regression models respectively.

          Results

          Overall retention rate was 76.9% (1685/2191), highest (89%) among participants who had spent 5+ years in the community and lowest (54.1%) among those with <1 year stay. Significant predictors of retention included tribe/ethnicity, baseline HIV negative status, and longer than 1 year stay in the community. Overall WTP was 89.1% (1953/2191). Lack of WTP was significantly higher among women than men [adj.OR = 1.51 (95% CI, 1.14- 2.00)] and among participants who had stayed in fishing communities for 10 or more years relative to those with less than one year [adj.OR = 1.78 (95% CI, 1.11 - 2.88)]. Overall HIV incidence rate per 100 pyar was 3.39 (95% CI; 2.55 - 4.49). Participants aged 25–29 years had highest incidence rates (4.61 - 7.67/100 pyar) and high retention rates between 78.5 and 83.1%. In a combined analysis of retention and incidence rates participants aged 30+ years had retention rates ~80% but low incidence rates (2.45 - 3.57 per 100 pyar) while those aged 25–29 years had the highest incidence rates (4.61 - 7.67/100 pyar) and retention rates 78.5 - 83.1%.

          Conclusions

          There is high HIV incidence, retention and WTP among fishing communities around L. Victoria, Uganda which make these communities appropriate for future HIV prevention efficacy studies including vaccine trials.

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          Most cited references25

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          Applied Logistic Regression

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            HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis.

            In the Step Study, the MRKAd5 HIV-1 gag/pol/nef vaccine did not reduce plasma viraemia after infection, and HIV-1 incidence was higher in vaccine-treated than in placebo-treated men with pre-existing adenovirus serotype 5 (Ad5) immunity. We assessed vaccine-induced immunity and its potential contributions to infection risk. To assess immunogenicity, we characterised HIV-specific T cells ex vivo with validated interferon-gamma ELISPOT and intracellular cytokine staining assays, using a case-cohort design. To establish effects of vaccine and pre-existing Ad5 immunity on infection risk, we undertook flow cytometric studies to measure Ad5-specific T cells and circulating activated (Ki-67+/BcL-2(lo)) CD4+ T cells expressing CCR5. We detected interferon-gamma-secreting HIV-specific T cells (range 163/10(6) to 686/10(6) peripheral blood mononuclear cells) ex vivo by ELISPOT in 77% (258/354) of people receiving vaccine; 218 of 354 (62%) recognised two to three HIV proteins. We identified HIV-specific CD4+ T cells by intracellular cytokine staining in 58 of 142 (41%) people. In those with reactive CD4+ T cells, the median percentage of CD4+ T cells expressing interleukin 2 was 88%, and the median co-expression of interferon gamma or tumor necrosis factor alpha (TNFalpha), or both, was 72%. We noted HIV-specific CD8+ T cells (range 0.4-1.0%) in 117 of 160 (73%) participants, expressing predominantly either interferon gamma alone or with TNFalpha. Vaccine-induced HIV-specific immunity, including response rate, magnitude, and cytokine profile, did not differ between vaccinated male cases (before infection) and non-cases. Ad5-specific T cells were lower in cases than in non-cases in several subgroup analyses. The percentage of circulating Ki-67+BcL-2(lo)/CCR5+CD4+ T cells did not differ between cases and non-cases. Consistent with previous trials, the MRKAd5 HIV-1 gag/pol/nef vaccine was highly immunogenic for inducing HIV-specific CD8+ T cells. Our findings suggest that future candidate vaccines have to elicit responses that either exceed in magnitude or differ in breadth or function from those recorded in this trial.
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              Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group.

              The study tested the hypothesis that community-level control of sexually transmitted disease (STD) would result in lower incidence of HIV-1 infection in comparison with control communities. This randomised, controlled, single-masked, community-based trial of intensive STD control, via home-based mass antibiotic treatment, took place in Rakai District, Uganda. Ten community clusters were randomly assigned to intervention or control groups. All consenting residents aged 15-59 years were enrolled; visited in the home every 10 months; interviewed; asked to provide biological samples for assessment of HIV-1 infection and STDs; and were provided with mass treatment (azithromycin, ciprofloxacin, metronidazole in the intervention group, vitamins/anthelmintic drug in the control). Intention-to-treat analyses used multivariate, paired, cluster-adjusted rate ratios. The baseline prevalence of HIV-1 infection was 15.9%. 6602 HIV-1-negative individuals were enrolled in the intervention group and 6124 in the control group. 75.0% of intervention-group and 72.6% of control-group participants provided at least one follow-up sample for HIV-1 testing. At enrolment, the two treatment groups were similar in STD prevalence rates. At 20-month follow-up, the prevalences of syphilis (352/6238 [5.6%]) vs 359/5284 [6.8%]; rate ratio 0.80 [95% CI 0.71-0.89]) and trichomoniasis (182/1968 [9.3%] vs 261/1815 [14.4%]; rate ratio 0.59 [0.38-0.91]) were significantly lower in the intervention group than in the control group. The incidence of HIV-1 infection was 1.5 per 100 person-years in both groups (rate ratio 0.97 [0.81-1.16]). In pregnant women, the follow-up prevalences of trichomoniasis, bacterial vaginosis, gonorrhoea, and chlamydia infection were significantly lower in the intervention group than in the control group. No effect of the intervention on incidence of HIV-1 infection was observed in pregnant women or in stratified analyses. We observed no effect of the STD intervention on the incidence of HIV-1 infection. In the Rakai population, a substantial proportion of HIV-1 acquisition appears to occur independently of treatable STD cofactors.
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                Author and article information

                Contributors
                nkiwanuka@gmail.com
                jmpendo@iavi.or.ug
                analutaaya@iavi.or.ug
                mwambuzi@iavi.or.ug
                ananvubya@iavi.or.ug
                pkato@iavi.or.ug
                EMuyanja@iavi.or.ug
                jssempiira@iavi.or.ug
                ABalyegisawa@iavi.org
                assetaala@iavi.or.ug
                Journal
                BMC Public Health
                BMC Public Health
                BMC Public Health
                BioMed Central (London )
                1471-2458
                22 September 2014
                22 September 2014
                2014
                : 14
                : 1
                : 986
                Affiliations
                [ ]Uganda Virus Research Institute-International AIDS Vaccine Initiate HIV Vaccine Program, Entebbe, Uganda
                [ ]International AIDS Vaccine Initiative (IAVI), New York, USA
                [ ]Department of Epidemiology and Biostatistics, College of Health Sciences, School of Public Health, Makerere University, Kampala, Uganda
                Article
                7127
                10.1186/1471-2458-14-986
                4194358
                25242015
                fa3b174f-b4bc-4cda-b82c-f42e4781fe03
                © Kiwanuka et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 9 July 2014
                : 18 September 2014
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2014

                Public health
                hiv-1 incidence,retention,willingness to participate,fishing communities,uganda
                Public health
                hiv-1 incidence, retention, willingness to participate, fishing communities, uganda

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