Medical Research Council MRC Uganda Virus Research Institute UVRI Uganda Research Unit on AIDS

Entebbe, Uganda

Medical Research Council MRC Uganda Virus Research Institute UVRI Uganda Research Unit on AIDS

Entebbe, Uganda

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PubMed | University of California at San Francisco, Emory University, Medical Research Council MRC Uganda Virus Research Institute UVRI Uganda Research Unit on AIDS, Zambia Emory HIV Research Project ZEHRP and Projet San Francisco PSF
Type: Journal Article | Journal: PloS one | Year: 2014

To investigate the effect of seasonal variation on adult clinical laboratory parameters in Rwanda, Zambia, and Uganda and determine its implications for HIV prevention and other clinical trials.Volunteers in a cross-sectional study to establish laboratory reference intervals were asked to return for a seasonal visit after the local season had changed from dry to rainy or vice versa. Volunteers had to be clinically healthy, not pregnant and negative for HIV, Hepatitis B and C, and syphilis infection at both visits. At each visit, blood was taken for measurement of hemoglobin, haematocrit, mean corpuscular volume, red blood cells, platelets, total white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils, CD4/CD8 T cells, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, direct bilirubin, total bilirubin, total immunoglobulin gamma, total protein, creatinine, total amylase, creatine phosphokinase and lactate dehydrogenase (LDH). Consensus dry season reference intervals were applied to rainy season values (and vice versa) and the proportion of out-of-range values determined. Percentage differences between dry and rainy season parameter mean values were estimated.In this cohort of 903 volunteers, less than 10.0% of consensus parameter (except LDH) values in one season were out-of-range in the other. Twenty-two (22) percent of rainy season LDH values fell outside of the consensus dry season interval with the higher values observed in the rainy season. Variability between consensus seasonal means ranged from 0.0% (total WBC, neutrophils, monocytes, basophils, and direct bilirubin) to 40.0% (eosinophils). Within sites, the largest seasonal variations were observed for monocytes (Masaka, 11.5%), LDH (Lusaka, 21.7%), and basophils (Kigali, 22.2%).Seasonality had minimal impact on adult clinical laboratory parameter values in Rwanda, Zambia, and Uganda. Seasonal variation may not be an important factor in the evaluation of adult clinical laboratory parameters in HIV prevention and other clinical trials in these countries.


Biraro S.,Medical Research Council MRC Uganda Virus Research Institute UVRI Uganda Research Unit on AIDS | Biraro S.,London School of Hygiene and Tropical Medicine | Ruzagira E.,Medical Research Council MRC Uganda Virus Research Institute UVRI Uganda Research Unit on AIDS | Kamali A.,Medical Research Council MRC Uganda Virus Research Institute UVRI Uganda Research Unit on AIDS | And 4 more authors.
PLoS ONE | Year: 2013

Background: Early initiation of antiretroviral therapy reduces risk of transmission to the uninfected partner in HIV discordant couples, but there are relatively little observational data on HIV transmission within couples from non-trial settings. The aims of this paper are to estimate HIV incidence among HIV discordant couples using longstanding observational data from a rural Ugandan population and to identify factors associated with HIV transmission within couples, including the role of HSV-2 infection. Methods: Using existing data collected at population-wide annual serological and behavioural surveys in a rural district in southwest Uganda between 1989 and 2007, HIV discordant partners were identified. Stored serum samples were tested for HSV-2 serostatus using the Kalon ELISA test. HIV seroconversion rates and factors association with HIV seroconversion were analysed using Poisson regression. Results: HIV status of both partners was known in 2465 couples and of these 259 (10.5%) were HIV serodiscordant. At enrolment, HSV-2 prevalence was 87.3% in HIV positive partners and 71.5% in HIV negative partners. Of the 259 discordant couples, 62 converted to HIV (seroconversion rate 7.11/100 PYAR, 95%CI; 5.54, 9.11) with the rate decreasing from 10.89 in 1990-1994 to 4.32 in 2005-2007. Factors independently associated with HIV seroconversion were female sex, non-Muslim religion, greater age difference (man older than woman by more than 15 years), higher viral load in the positive partner and earlier calendar period. HSV-2 was not independently associated with HIV acquisition (HR 1.62, 95%CI; 0.57, 4.55) or transmission (HR 0.61, 95%CI; 0.24, 1.57). No transmissions occurred in the 29 couples where the index partner was on ART during follow up (872 person-years on ART). Discussion: HIV negative partners in serodiscordant couples have a high incidence of HIV if the index partner is not on antiretroviral therapy and should be provided with interventions such as couple counselling, condoms and antiretroviral treatment. © 2013 Biraro et al.


PubMed | Medical Research Council MRC Uganda Virus Research Institute UVRI Uganda Research Unit on AIDS
Type: Journal Article | Journal: PloS one | Year: 2011

To determine the incidence of and risk factors for HIV acquisition in a cohort of HIV-uninfected partners from HIV discordant couples in Masaka, Uganda, and to establish its suitability for HIV vaccine trials.HIV-uninfected adults living in HIV discordant couple relationships were enrolled and followed for 2 years. Interviews, medical investigations, HIV counseling and testing, syphilis and urine pregnancy (women) tests were performed at quarterly visits. Sexual risk behaviour data were collected every 6 months.495 participants were enrolled, of whom 34 seroconverted during 786.6 person-years of observation (PYO). The overall HIV incidence rate [95% confidence interval (CI)] was 4.3 [3.1-6]; and 4.3 [2.8-6.4] and 4.4 [2.5-8] per 100 PYO in men and women respectively. Independent baseline predictors for HIV acquisition were young age [18-24 (aRR=4.1, 95% CI 1.6-10.8) and 25-34 (aRR=2.7, 95% CI 1.2-5.8) years]; alcohol use (aRR=2.6, 95% CI 1.1-6); and reported genital discharge (aRR=3.4, 95% CI 1.6-7.2) in the past year. Condom use frequency in the year preceding enrolment was predictive of a reduced risk of HIV acquisition [sometimes (aRR=0.4, 95% CI 0.2-0.8); always (aRR=0.1, 95% CI 0.02-0.9)]. In the follow-up risk analysis, young age [18-24 (aRR=6.2, 95% CI 2.2-17.3) and 25-34 (aRR=2.3, 95% CI 1.1-5.0) years], reported genital discharge (aRR=2.5, 95% CI 1.1-5.5), serological syphilis (aRR 3.2, 95% CI 1.3-7.7) and the partner being ART nave (aRR=4.8, 95% CI 1.4-16.0) were independently associated with HIV acquisition. There were no seroconversions among participants who reported consistent condom use during the study.The study has identified important risk factors for HIV acquisition among HIV discordant couples. HIV-uninfected partners in discordant couples may be a suitable population for HIV vaccine efficacy trials. However, recent confirmation that ART reduces heterosexual HIV transmission may make it unfeasible to conduct HIV prevention trials in this population.


PubMed | Medical Research Council MRC Uganda Virus Research Institute UVRI Uganda Research Unit on AIDS
Type: Journal Article | Journal: PloS one | Year: 2013

Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens.Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment.Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN- ELISPOT.Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen.Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing.Clinicaltrials.gov number NCT00931346.


PubMed | Medical Research Council MRC Uganda Virus Research Institute UVRI Uganda Research Unit on AIDS
Type: Journal Article | Journal: Tropical medicine & international health : TM & IH | Year: 2012

To investigate antiretroviral therapy (ART) uptake after its introduction in 2004 in a longitudinal population-based cohort and its nested clinical cohort in rural Uganda.A HIV serosurvey of all adults aged 15 years is conducted annually. Two intervals were selected for analysis. Interval 1 (November 2004-October 2006) provided 2 years of follow-up to prospectively evaluate access to HIV services. Interval 2 (November 2007-October 2008) was used to evaluate current coverage of services. Logistic regression was used to identify sociodemographic factors associated with ART screening within 2 years of diagnosis. ART coverage was assessed using Weibull survival models to estimate the numbers needing ART.In Interval 1, 636 HIV-positive adults were resident and 295 (46.4%) knew their status. Of those, 248 (84.1%) were screened for ART within 2 years of diagnosis. After adjusting for age, those who were widowed, separated or never married were more likely to be screened than those who were married. In Interval 2, 575 HIV-positive adults were residents, 322 (56.0%) knew their status, 255 (44.3%) had been screened for ART and 189 (32.9%) had started ART. Estimated ART coverage was 66%.In this cohort, ART access and uptake is very high once people are diagnosed. Owing to intensive screening in the study clinic, nearly all participants who were eligible initiated ART. However, this is unlikely to reflect coverage in the general population, intensified efforts are needed to promote HIV testing, and ART screening and uptake are needed among those found to be HIV-positive.


PubMed | Medical Research Council MRC Uganda Virus Research Institute UVRI Uganda Research Unit on AIDS
Type: | Journal: Health research policy and systems | Year: 2011

With rapidly increasing globalization, trends towards unhealthy diets, obesity, sedentary lifestyles and unhealthy habits are resulting in an increased worldwide burden of chronic non-communicable diseases (NCDs). In Africa this means that health systems face the challenge of an increasing burden of NCDs and of continuing high morbidity and mortality from communicable diseases. This health transition represents an enormous challenge to Africa as the region with the least resources for an effective response. Whereas previous epidemics, including HIV, have caught Africa unprepared, the opportunity now arises to take the advancing wave of health transition in Africa seriously. Health research has a key role to play in meeting health and development goals, and must be responsive to changing disease patterns, such as health transition. There is an urgent need for research on health transition in Africa to enable countries to respond effectively to rapidly changing health needs.Key areas of research include the following: epidemiological research so that a good understanding of the distribution in Africa of communicable and non-communicable diseases can inform health planning; research on the interactions between communicable and non-communicable diseases; health system research with a particular focus on new approaches to improve the primary care response to health transition; and policy research to evaluate the more upstream measures addressing the population-level determinants of NCDs. It is time to capitalise on the global policy environment, which is becoming more favourable to action on health transition in Africa, and implement a research agenda for health transition. Alliances have a key role to play in Africa as well as in other regions in implementing the research agenda on health transition by building research capacity and mobilizing the necessary investments.


PubMed | Medical Research Council MRC Uganda Virus Research Institute UVRI Uganda Research Unit on AIDS
Type: Journal Article | Journal: Journal of acquired immune deficiency syndromes (1999) | Year: 2011

The role of concurrent sexual partnerships in the HIV epidemic in sub-Saharan Africa is not well understood. Although most infections in Africa occur among married individuals, transmission may occur from both spousal and extraspousal partnerships. This article explores extraspousal partnerships as a form of concurrency, examining the association with HIV status, demographic characteristics, and sexual behaviors in a population-based cohort in rural Uganda.Prevalence of extraspousal partnerships was estimated using cross-sectional data from 2008, and adjusted odds ratios (aOR) were estimated for factors associated with the prevalence of extraspousal partnerships using logistic regression. Among men who were not in polygynous marriages, we used linked spousal data to investigate the association between extraspousal partnerships and wives serostatus.Extraspousal partnerships in the past year were reported by 17% of married men and 2% of married women. Among both men and women, extraspousal partnerships were associated with not knowing their partners HIV status (men: aOR = 1.74; 95% CI: 1.13 to 2.67; women: aOR = 1.76; 95% CI: 1.13 to 2.75), and extraspousal partnerships were also associated with increased condom use for men. There was no evidence that men reporting extraspousal partnerships were at increased risk of HIV (aOR = 0.98; 95% CI: 0.48 to 2.01), or that a womans risk of HIV was associated with her husband reporting extraspousal partnerships (aOR = 0.68; 95% CI: 0.29 to 1.57).For both men and women, extraspousal partnerships were associated with not knowing their partners HIV status. There was no evidence of an association of extraspousal partnerships with HIV serostatus in this cross-sectional analysis.


PubMed | Medical Research Council MRC Uganda Virus Research Institute UVRI Uganda Research Unit on AIDS
Type: Journal Article | Journal: The Lancet. Infectious diseases | Year: 2011

Cryptococcal disease remains an important cause of morbidity and mortality in HIV-infected individuals in sub-Saharan Africa, despite the introduction of antiretroviral therapy. We studied fluconazole as primary prophylaxis against cryptococcal disease in patients awaiting or starting antiretroviral therapy in Uganda.In this prospective, double-blind randomised controlled trial, we enrolled HIV-positive adults with CD4 counts less than 200 cells per L, cryptococcal antigen (CrAg)-negative, naive for antiretroviral therapy, and coming from five local AIDS organisations in Masaka district, Uganda. Enrolment took place between Sept 14, 2004, and Feb 1, 2008. Participants were randomly allocated to placebo or 200 mg fluconazole three times per week (1:1) in blocks of 40. Randomisation was done with ralloc procedure in Stata. Participants were reviewed after 4 weeks and referred for antiretroviral therapy, then seen every 8 weeks. Participants discontinued trial treatment when CD4 counts reached 200 cells per L (median 197 days). Primary endpoints were invasive cryptococcal disease and all-cause mortality. Secondary endpoints were time to first episode and incidence of oesophageal candidosis, time to first episode and incidence of oropharyngeal or vaginal candidosis, and time to first hospital admission or death. The primary safety endpoint was cessation of trial drug because of transaminase concentrations higher than five times the upper limit of normal (ULN), or other major adverse events. Analyses were done by intention to treat and included all participants enrolled in the trial. Participants and researchers were masked to group assignment. This trial is registered with controlled-trials.com, number ISRCTN 76481529.Of 1519 individuals enrolled, 760 participants received fluconazole and 759 received placebo. 19 developed cryptococcal disease, one in the fluconazole group and 18 in the placebo group (p=00001); adjusted HR (aHR) 187 (95% CI 25-1407). One case of cryptococcal disease could be prevented by treating 446 patients with baseline CD4 counts lower than 200 cells per L. Fluconazole was effective against cryptococcal disease both before (aHR=110 [14-853]) and after start of antiretroviral therapy (no cases in fluconazole vs seven cases on placebo). Seven participants died from cryptococcal disease, none in the fluconazole group. All-cause mortality (n=189) did not differ between the two groups (p=046). Fluconazole reduced the time to first episode of oesophageal, and oropharyngeal and vaginal candidosis, as well as the incidence of all candidosis (p<00001), but had no effect on hospital admission or death. The frequency of elevated transaminases (>5ULN) was similar between groups (aHR=094 [065-135]).Fluconazole was safe and effective as primary prophylaxis against cryptococcal disease, both before and during early antiretroviral treatment. Cryptococcal infection was less common than anticipated because of the rapid commencement of antiretroviral therapy and exclusion of those with positive CrAg. In patients with negative CrAg on screening, fluconazole prophylaxis can prevent cryptococcal disease while waiting for and in the early weeks of antiretroviral therapy, particularly in those with CD4 counts of less than 100 cells per L.Medical Research Council, UK, and Rockefeller Foundation.


PubMed | Medical Research Council MRC Uganda Virus Research Institute UVRI Uganda Research Unit on AIDS
Type: Journal Article | Journal: Tropical medicine & international health : TM & IH | Year: 2012

The choice of research method relevant to the evaluation of delivery of a health intervention is not always straightforward. We use the evaluation of HIV and tuberculosis community treatment supporters in promoting adherence to treatment in Africa as a case study to illustrate the pros and cons of operational research and randomised controlled trials. The choice of this intervention for the case study reflects the importance of maximising the benefits of unprecedented efforts to scale-up treatments of these two epidemics. International policy supporting the role of community treatment supporters in tuberculosis is largely based on the findings of operational research studies. This reflects the advantages that operational research is less costly than randomised controlled trials, provides more rapid answers to policy questions, enables standard evaluation of the intervention in real life conditions in several diverse settings and has in-built potential to influence policy and practice, because the research is conducted within health programmes. Recent evidence on the role of community treatment supporters in HIV is largely based on randomised trials. This reflects the advantages that randomised trials compared to operational research are more rigorous and generate a more convincing result. Operational research and randomised trials may be viewed as providing complementary findings to inform new policies and practice aimed at improving programme performance and patient outcomes. However, in practice, insufficient funds are likely to be made available for randomised trials to answer all the current research questions on delivery of programme interventions. In deciding on the type of research to evaluate a particular health intervention, dialogue is necessary with policy-makers to weigh up explicitly the trade-offs between research rigour and other factors such as cost, speed of implementation of research and speed of policy uptake and of change in programme practice.


PubMed | Medical Research Council MRC Uganda Virus Research Institute UVRI Uganda Research Unit on AIDS
Type: Journal Article | Journal: Sexually transmitted infections | Year: 2011

Recent publications suggest that fishing populations may be highly affected by the HIV epidemic. However, accurate data are scarce. The authors determined HIV and syphilis prevalence and associated risk factors in a fishing population of Lake Victoria in Uganda.10,188 volunteers aged 13 years from a census carried out in five fishing communities between February and August 2009 were invited to attend central study clinics established in each community. After informed consent, 2005 randomly selected volunteers responded to socio-demographic and risk assessment questions, provided blood for HIV testing and 1618 volunteers were also tested for syphilis. Risk factors were analysed using logistic regression.HIV and active syphilis (rapid plasma reagin titre 1:8) prevalences were 28.8% (95% CI 26.8 to 30.8) and 4.3% (95% CI 3.3 to 5.4), respectively, and high risk sexual behaviour was frequently reported. HIV prevalence was independently associated with female sex, increasing age, occupation (highest in fishermen), relationship to household head, self-reported genital sores and knowledge of an HIV infected partner. Alcohol consumption, syphilis and sexually transmitted infections (STIs) reported by health workers were associated with HIV in women, and genital discharge and inconsistent condom use in men. Syphilis prevalence was independently associated with age and alcohol consumption in women, and recent genital sores and sex under the influence of drugs in men.This fishing population characterised by a very high HIV prevalence, high syphilis prevalence and frequently reported sexual risk behaviours, urgently needs improved STI services and targeted behavioural interventions.

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