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Beardsley J.,University of Oxford | Wolbers M.,University of Oxford | Kibengo F.M.,UVRI Uganda Research Unit on AIDS | Ggayi A.-B.M.,UVRI Uganda Research Unit on AIDS | And 32 more authors.
New England Journal of Medicine | Year: 2016

BACKGROUND: Cryptococcal meningitis associated with human immunodeficiency virus (HIV) infection causes more than 600,000 deaths each year worldwide. Treatment has changed little in 20 years, and there are no imminent new anticryptococcal agents. The use of adjuvant glucocorticoids reduces mortality among patients with other forms of meningitis in some populations, but their use is untested in patients with cryptococcal meningitis. METHODS: In this double-blind, randomized, placebo-controlled trial, we recruited adult patients with HIV-associated cryptococcal meningitis in Vietnam, Thailand, Indonesia, Laos, Uganda, and Malawi. All the patients received either dexamethasone or placebo for 6 weeks, along with combination antifungal therapy with amphotericin B and fluconazole. RESULTS: The trial was stopped for safety reasons after the enrollment of 451 patients. Mortality was 47% in the dexamethasone group and 41% in the placebo group by 10 weeks (hazard ratio in the dexamethasone group, 1.11; 95% confidence interval [CI], 0.84 to 1.47; P = 0.45) and 57% and 49%, respectively, by 6 months (hazard ratio, 1.18; 95% CI, 0.91 to 1.53; P = 0.20). The percentage of patients with disability at 10 weeks was higher in the dexamethasone group than in the placebo group, with 13% versus 25% having a prespecified good outcome (odds ratio, 0.42; 95% CI, 0.25 to 0.69; P<0.001). Clinical adverse events were more common in the dexamethasone group than in the placebo group (667 vs. 494 events, P = 0.01), with more patients in the dexamethasone group having grade 3 or 4 infection (48 vs. 25 patients, P = 0.003), renal events (22 vs. 7, P = 0.004), and cardiac events (8 vs. 0, P = 0.004). Fungal clearance in cerebrospinal fluid was slower in the dexamethasone group. Results were consistent across Asian and African sites. CONCLUSIONS: Dexamethasone did not reduce mortality among patients with HIV-associated cryptococcal meningitis and was associated with more adverse events and disability than was placebo. © Copyright 2016 Massachusetts Medical Society.


Bond V.,London School of Hygiene and Tropical Medicine | Bond V.,University of Zambia | Hoddinott G.,Stellenbosch University | Viljoen L.,Stellenbosch University | And 4 more authors.
AIDS Patient Care and STDs | Year: 2016

Gauging community responses to the WHO 2015 recommendation to provide antiretroviral treatment (ART) to all people living with HIV (PLHIV) is critical. There is limited qualitative evidence on the acceptability of this Universal Test and Treat (UTT) strategy or community understanding of the impact of ART on reducing HIV transmission, promoted as Treatment as Prevention (TasP). This article explores early understanding of UTT and TasP in 21 urban communities in South Africa and Zambia in 2013 before a community randomized trial of combination prevention-HPTN 071 (PopART). It draws on participatory research conducted in each community, which carried out group discussions and interviews with 1202 respondents and 203 structured observations. Participants were largely unfamiliar with the concepts of UTT and TasP. They were concerned about an accompanying de-emphasis on sexual behavior change. Treatment and prevention seemed, at first glance, to be experienced separately. With the exception of the prevention of mother-to-child transmission, prevention seldom came into discussions about ART. This was partly because this science had not yet been explained to many and also because it was not an easy fit. Contemplating the link between treatment and prevention, participants emphasized both PLHIV taking care of themselves through good health and preventing disease progression and the moral responsibility of PLHIV to prevent HIV transmission. To avoid igniting moralizing and blaming when introducing UTT and TasP, we should capitalize on the "taking care of yourself" legacy while boosting public responsibility through broad antistigma education and patient empowerment efforts. © 2016 Virginia Bond et al. Published by Mary Ann Liebert, Inc.


Elliott A.M.,UVRI Uganda Research Unit on AIDS | Elliott A.M.,London School of Hygiene and Tropical Medicine | Mawa P.A.,UVRI Uganda Research Unit on AIDS | Webb E.L.,London School of Hygiene and Tropical Medicine | And 12 more authors.
Vaccine | Year: 2010

Some vaccines show poor efficacy in tropical countries. Within a birth cohort in Uganda, we investigated factors that might influence responses to BCG and tetanus immunisation. Whole blood assay responses to crude culture filtrate proteins of Mycobacterium tuberculosis (cCFP)) and tetanus toxoid (TT) were examined among 1506 and 1433 one-year-olds, respectively. Maternal Mansonella perstans infection was associated with higher interleukin (IL)-10 responses to both immunogens but no reduction in gamma interferon (IFN-γ), IL-5 and IL-13 responses; other maternal helminth infections showed little effect. Tetanus immunisation during pregnancy was associated with higher infant responses to TT; maternal BCG scar (from past immunisation) with lower infant IL-5 and IL-13 responses to cCFP. IFN-γ, IL-5 and IL-13 to TT were reduced in HIV-exposed-uninfected infants; infant malaria and HIV were associated with lower IFN-γ, IL-5 and IL-13 responses to both immunogens. We conclude that maternal helminth infections are unlikely to explain poor vaccine efficacy in the tropics. Effects of maternal immunisation on infant responses to vaccines should be explored. Prevention of infant malaria and HIV could contribute to effectiveness of immunisation programmes. © 2010 Elsevier Ltd.


Gilks C.F.,Imperial College London | Walker A.S.,MRC Clinical Trials Unit | Dunn D.T.,MRC Clinical Trials Unit | Gibb D.M.,MRC Clinical Trials Unit | And 11 more authors.
Antiviral Therapy | Year: 2012

Background: Boosted protease inhibitor (bPI) monotherapy (bPImono) potentially has substantial cost, safety and operational benefits. It has never been evaluated as second-line antiretroviral therapy (ART) in Africa. Methods: After 24 weeks of lopinavir/ritonavir-containing second-line therapy, DART participants were randomized to remain on combination therapy (CT), or change to bPImono maintenance (SARA trial; ISRCTN53817258). Joint primary end points were CD4+ T-cell changes 24 weeks later and serious adverse events (SAEs); retrospectively assayed viral load (VL) was a secondary end point. Analyses were intention-to-treat. Results: A total of 192 participants were randomized to CT (n=95) or bPImono (n=97) and followed for median 60 weeks (IQR 45-84). Participants received median 4.0 years (IQR 3.5-4.4) first-line ART. Median CD4+ T-cell count at first-line failure was 86 cells/mm 3 (47-136), increasing to 245 cells/mm3 (173-325) after 24-week induction when 77% had VL<50 copies/ml. Overall, 44 (23%) were receiving second-line therapy with bPI and nucleoside reverse transcriptase inhibitors (NRTI) only, and 148 (77%) with bPI plus non-NRTI (NNRTI) with or without NRTI. At 24 weeks after randomization to CT versus bPImono, mean CD4+ T-cell increase was 42 (CT, n=85) versus 49 cells/mm3 (bPImono, n=88; adjusted difference 13 [95% CI -15, 43], P=0.37; non-inferior compared with predetermined non-inferiority margin [-33]). Virological suppression was greater for CT versus bPImono (trend P=0.009): 77% (70/91) versus 60% (56/94) were <50 copies/ml, and 5% (5) versus 14% (13) were ≥1,000 copies/ml, respectively. A total of 0 (0%) versus 5 (5%) participants had major protease inhibitor mutations and 3 (3%) versus 0 (0%) new NNRTI/NRTI mutations were detected during follow-up. Two participants (1 CT and 1 bPImono) died >24 weeks after randomization, and 5 (2 CT and 3 bPImono) experienced SAEs (P=0.51). Conclusions: bPImono following a 24-week second-line induction was associated with similar CD4+ T-cell response, but increased low-level viraemia, generally without protease inhibitor resistance. Longer-term trials are needed to provide definitive evidence about effectiveness in Africa. ©2012 International Medical Press.


Mugisha J.O.,UVRI Uganda Research Unit on AIDS | Mugisha J.O.,London School of Hygiene and Tropical Medicine | Kuper H.,London School of Hygiene and Tropical Medicine | Seeley J.,UVRI Uganda Research Unit on AIDS | And 2 more authors.
Journal of Aging and Health | Year: 2014

Objective: To describe older people's perceptions of anemia in a rural Ugandan population. Method: Quantitative and qualitative data on anemia were collected from participants aged ≥50 years from January 2012 to January 2013 using questionnaires and in-depth interviews. Quantitative data were collected from 1,455 participants. Qualitative data were collected from 10 people who were purposively selected. Data were analyzed using STATA software and thematic content analysis. Results: 33.8% men and 17.4% women had anemia. Older people perceived themselves to be anemic because of symptoms and beliefs about causes. Those with anemia were more likely to perceive that they had anemia (18.4% vs. 10.2%, p <.001). Poor diet, diseases, poor living conditions, and over work were mentioned as causes of anemia. Use of traditional methods for treating anemia was common. Discussion: Anemia prevention and control programs in Uganda should target older people and correct misconceptions about the causes and treatment of anemia. © The Author(s) 2014.


Vandepitte J.,UVRI Uganda Research Unit on AIDS | Muller E.,South African National Institute for Communicable Diseases | Bukenya J.,UVRI Uganda Research Unit on AIDS | Nakubulwa S.,UVRI Uganda Research Unit on AIDS | And 5 more authors.
Journal of Infectious Diseases | Year: 2012

Background. The importance of Mycoplasma genitalium in human immunodeficiency virus (HIV)-burdened sub-Saharan Africa is relatively unknown. We assessed the prevalence and explored determinants of this emerging sexually transmitted infection (STI) in high-risk women in Uganda. Methods. Endocervical swabs from 1025 female sex workers in Kampala were tested for Mycoplasma genitalium using a commercial Real-TM polymerase chain reaction assay. Factors associated with prevalent Mycoplasma genitalium, including sociodemographics, reproductive history, risk behavior, and HIV and other STIs, were examined using multivariable logistic regression. Results. The prevalence of Mycoplasma genitalium was 14% and higher in HIV-positive women than in HIV-negative women (adjusted odds ratio [OR], 1.64; 95% confidence interval [CI], 1.12-2.41). Mycoplasma genitalium infection was less prevalent in older women (adjusted OR, 0.61; 95% CI,. 41-.90 for women ages 25-34 years vs <25 years; adjusted OR, 0.32; 95% CI,. 15-.71 for women ≥35 years vs those <25 years) and in those who had been pregnant but never had a live birth (adjusted OR, 2.25; 95% CI, 1.04-4.88). Mycoplasma genitalium was associated with Neisseria gonorrhoeae (adjusted OR, 1.84; 95% CI, 1.13-2.98) and with Candida infection (adjusted OR, 0.41; 95% CI,. 18-.91), and there was some evidence of association with Trichomonas vaginalis (adjusted OR, 1.56; 95% CI, 1.00-2.44). Conclusions. The relatively high prevalence of Mycoplasma genitalium and its association with prevalent HIV urgently calls for further research to explore the potential role this emerging STI plays in the acquisition and transmission of HIV infection. © 2011 The Author.


Kazooba P.,UVRI Uganda Research Unit on AIDS | Kasamba I.,UVRI Uganda Research Unit on AIDS | Baisley K.,London School of Hygiene and Tropical Medicine | Mayanja B.N.,UVRI Uganda Research Unit on AIDS | And 2 more authors.
Tropical Medicine and International Health | Year: 2012

Objectives 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. Methods A HIV serosurvey of all adults aged ≥15years is conducted annually. Two intervals were selected for analysis. Interval 1 (November 2004-October 2006) provided 2years 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 2years of diagnosis. ART coverage was assessed using Weibull survival models to estimate the numbers needing ART. Results 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 2years 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%. Conclusions 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. © 2012 Blackwell Publishing Ltd.


Webb E.L.,London School of Hygiene and Tropical Medicine | Mawa P.A.,UVRI Uganda Research Unit on AIDS | Ndibazza J.,UVRI Uganda Research Unit on AIDS | Kizito D.,UVRI Uganda Research Unit on AIDS | And 23 more authors.
The Lancet | Year: 2011

Helminth infections affect the human immune response. We investigated whether prenatal exposure to and treatment of maternal helminth infections affects development of an infant's immune response to immunisations and unrelated infections. In this randomised, double-blind, placebo-controlled trial, we enrolled 2507 women in the second or third trimester of pregnancy who were planning to deliver in Entebbe General Hospital, Entebbe, Uganda. With a computer-generated random number sequence in blocks of 100, we assigned patients to 440 mg albendazole and 40 mg/kg praziquantel (n=628), 440 mg albendazole and a praziquantel-matching placebo (n=625), 40 mg/kg praziquantel and an albendazole-matching placebo (n=626), or an albendazole-matching placebo and praziquantel-matching placebo (n=628). All participants and hospital staff were masked to allocation. Primary outcomes were immune response at age 1 year to BCG, tetanus, and measles immunisation; incidence of infectious diseases during infancy; and vertical HIV transmission. Analysis was by intention-to-treat. This trial is registered, number ISRCTN32849447. Data were available at delivery for 2356 women, with 2345 livebirths; 2115 (90) of liveborn infants remained in follow-up at 1 year of age. Neither albendazole nor praziquantel treatments affected infant response to BCG, tetanus, or measles immunisation. However, in infants of mothers with hookworm infection, albendazole treatment reduced interleukin-5 (geometric mean ratio 0·50, 95 CI 0·30-0·81, interaction p=0·02) and interleukin-13 (0·52, 0·34- 0·82, 0·0005) response to tetanus toxoid. The rate per 100 person-years of malaria was 40·9 (95 CI 38·3-43·7), of diarrhoea was 134·1 (129·2-139·2), and of pneumonia was 22·3 (20·4-24·4). We noted no effect on infectious disease incidence for albendazole treatment (malaria [hazard ratio 0·95, 95 CI 0·79-1.14], diarrhoea [1·06, 0·96-1·16], pneumonia [1·11, 0·90-1·38]) or praziquantel treatment (malaria [1·00, 0·84-1·20], diarrhoea [1·07, 0·98-1·18], pneumonia [1·00, 0·80-1·24]). In HIV-exposed infants, 39 (18) were infected at 6 weeks; vertical transmission was not associated with albendazole (odds ratio 0·70, 95 CI 0·35-1·42) or praziquantel (0·60, 0·29-1·23) treatment. These results do not accord with the recently advocated policy of routine antenatal anthelmintic treatment, and the value of such a policy may need to be reviewed. Wellcome Trust. © 2011 Elsevier Ltd.


Hjelmeland H.,Norwegian University of Science and Technology | Hjelmeland H.,Norwegian Institute of Public Health | Kinyanda E.,UVRI Uganda Research Unit on AIDS | Knizek B.L.,Norwegian University of Science and Technology
Medicine, Science and the Law | Year: 2012

Attempted suicide is still criminalized in Uganda. However, the Ministry of Health has asked the psychiatric community to help in the work to abolish this law. The purpose of this study was to investigate how Ugandan mental health workers view this law. We conducted a qualitative interview study of 30 mental health workers (psychiatrists, psychologists, psychiatric clinical officers and psychiatric nurses). We found that two-thirds of this sample wanted the law abolished, mainly because they view suicidal behaviour as a mental health issue. Some, however, wanted to keep the law because they viewed it as a suicide prevention in that it would deter people from killing themselves. A few were ambivalent. The findings indicate a need for increased awareness of the negative consequences of the law as well as educating mental health workers in understanding of suicidal behaviour and suicidal people.

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