NRU :: Browsing by Author "Reynolds, Steven J."

Browsing by Author "Reynolds, Steven J."

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Alcohol use and alcohol-related consequences are associated with not being virally suppressed among persons living with HIV in the Rakai region of Uganda
(Drug and Alcohol Dependence, 2021) Miller, Amanda P.; Pitpitan, Eileen V.; Kiene, Susan M.; Raj, Anita; Jain, Sonia; Luisa Zuniga, Marıa; Nabulaku, Dorean; Nalugoda, Fred; Ssekubugu, Robert; Nantume, Betty; Kigozi, Godfrey; Sewankambo, Nelson K.; Kagaayi, Joseph; Reynolds, Steven J.; Grabowski, Kate; Wawer, Maria; Wagman, Jennifer A.
Background: Alcohol use is common among persons living with HIV (PWH) in Uganda and associated with poor HIV care outcomes; findings regarding the relationship between alcohol use and viral suppression (VS) have been inconclusive. Methods: Data from two rounds (2017-2020) of the Rakai Community Cohort Study, an open population-based cohort study in the Rakai region, Uganda, were analyzed. Two alcohol exposures were explored: past year alcohol use and alcohol-related consequences. Multivariable models (GEE) were used to estimate associations between alcohol exposures and VS for the overall sample and stratified by sex, adjusting for repeated measurement. Causal mediation by ART use was explored. Results: Over half (55%) of participants (n=3,823 PWH) reported alcohol use at baseline; 37.8% of those reporting alcohol use reported alcohol-related consequences. ART use and VS at baseline significantly differed by alcohol use with person reporting alcohol use being less likely to be on ART or VS. Alcohol use was significantly associated with decreased odds of VS among women but not men (adj. OR 0.72 95% CI 0.58-0.89, p=0.0031). However, among males who use alcohol, experiencing alcohol-related consequences was significantly associated with decreased odds of VS (adj. OR 0.69 95% CI 0.54-0.88, p=0.0034). The relationships between both alcohol exposures and VS were not significant in models restricted to persons on ART. Conclusions: We provide sex-stratified estimates of associations between two alcohol measures and VS in the context of current HIV treatment guidelines. This study confirms that alcohol use is adversely associated with VS but ART use mediates this pathway, suggesting that initiation and retention on ART are critical steps to addressing alcohol-related disparities in VS.
Antiretroviral concentration measurements as an additional tool to manage virologic failure in resource limited settings: a case control study
(AIDS research and therapy, 2019) Buzibye, Allan; Musaazi, Joseph; Braun, Amrei von; Nanzigu, Sarah; Sekaggya‑Wiltshire, Christine; Kambugu, Andrew; Fehr, Jan; Lamorde, Mohammed; Gutteck, Ursula; Muller, Daniel; Sowinski, Stefanie; Reynolds, Steven J.; Castelnuovo, Barbara
Several studies demonstrate a correlation between sub-therapeutic concentrations of antiretroviral drugs and virologic failure. We examined the sensitivity, specificity and predictive values of sub-therapeutic drug levels in predicting viralogic failure. Methods: This was a case control study with cases being samples of participants with virologic failure, and controls samples of participants with virologic suppression. We analyzed samples obtained from participants that had been on antiretroviral treatment (ART) for at least 6 months. Virologic failure was defined as HIV-RNA viral load ≥ 1000 copies/ ml. Sub-therapeutic drug levels were defined according to published reference cutoffs. The diagnostic validity of drug levels for virologic failure was assessed using plasma viral loads as a gold standard. Results: Sub-therapeutic ART concentrations explained only 38.2% of virologic failure with a probability of experiencing virologic failure of 0.66 in a patient with low drug levels versus 0.25 for participants with measurements within or above the normal range. Approximately 90% of participants with ART concentrations above the lower clinical cut off did not have virologic failure. Conclusions: These results support prior indication for therapeutic drug monitoring in cases of suspected virologic failure.
Antiretroviral Therapy is Highly Effective Against Incident Hepatitis B Disease Acquisition Among HIV-Infected Adults in Rakai, Uganda
(American Society of Clinical Oncology, 2016) Seremba, Emmanuel; Ssempijja, Victor; Kalibbala, Sarah; Gray, Ronald; Wawer, Maria; Nalugoda, Fred; Casper, Corey; Phipps, Warren T.; Ocama, Ponsiano; Thomas, David L.; Reynolds, Steven J.
Co-infection with HepatitisB(HBV) and HIV iscommonin sub-Saharan Africa (SSA) and accelerates progression of liver disease to cirrhosis, hepatocellular carcinoma (HCC) andother complications. About 60% of HCC in Africa is attributed to HBV. In Uganda, 80% of HCC patients have HBVand20%have HIV/HBV coinfection.HCCis the 4th commonest cancer among Ugandan males and the 6th commonest in females. It is almost always a fatal malignancy in SSA. Prevention of HBV is best achieved through vaccination. Vaccination of HIV-infected adults for HBV is standard of care in developed countries but not in SSA where HBV is believed to be acquired in childhood and where there is lack of HBV incidence data. We investigated the incidence and risk factors associated with HBV among HIV-infected adults in Rakai, Uganda.
Association of Medical Male Circumcision and Antiretroviral Therapy Scale-up With Community HIV Incidence in Rakai,Uganda
(American Medical Association, 2016) Kong, Xiangrong; Kigozi, Godfrey; Ssekasanvu, Joseph; Nalugoda, Fred; Nakigozi, Gertrude; Ndyanabo, Anthony; Lutalo, Tom; Reynolds, Steven J.; Ssekubugu, Robert; Kagaayi, Joseph; Bugos, Eva; Chang, Larry W.; Nanlesta, Pilgrim; Mary, Grabowski; Berman, Amanda; Quinn, Thomas C.; Serwadda, David; Wawer, Maria J.; Gray, Ronald H.
Randomized trials have shown that medical male circumcision( MMC)reduces maleHIVacquisition by50% to 60%,1-3 and that early initiation of antiretroviral therapy (ART) reduces HIV transmission by more than90%in HIV-discordant couples.4Mathematical modeling suggests that these interventions could mitigate the HIV epidemic in sub- Saharan Africa,5-7 but there is limited empirical evidence for the population-level effects of these interventions on HIV incidence in real-world programs. MMC provides direct protection against male HIV acquisition by removing the foreskin, which is rich in HIV target cells.8-10 The potential effect ofMMCon population-level HIV incidence depends on this biological effect, the level ofMMC coverage, risk profiles ofmenacceptingMMC,and whether behavioral disinhibition occurs following circumcision.
A case-control study of Burkitt lymphoma in East Africa: are local health facilities an appropriate source of representative controls?
(Infectious Agents and Cancer, 2012) Baik, Sonya; Mbaziira, Mike; Williams, Makeda; Ogwang, Martin D.; Kinyera, Tobias; Emmanuel, Benjamin; Ziegler, John L.; Reynolds, Steven J.; Mbulaiteye, Sam M.
We investigated the feasibility and appropriateness of enrolling controls for Burkitt lymphoma (BL) from local health facilities in two regions in Uganda. Methods: BL case data were compiled from two local hospitals with capacity to diagnose and treat BL in Northwest and North-central regions of Uganda during 1997 to 2009. Local health facility data were compiled from children attending four representative local health facilities in the two regions over a two week period in May/June 2010. Age and sex patterns of BL cases and children at local facilities were compared and contrasted using frequency tables. Results: There were 999 BL cases diagnosed in the study area (92% of all BL cases treated at the hospitals): 64% were from North-central and 36% from North-west region. The mean age of BL cases was 7.0 years (standard deviation [SD] 3.0). Boys were younger than girls (6.6 years versus 7.2 years, P = 0.004) and cases from North-central region were younger than cases from North-west region (6.8 years versus 7.3 years, P = 0.014). There were 1012 children recorded at the four local health facilities: 91% at facilities in North-central region and 9% from facilities in North-west region. Daily attendance varied between 1 to 75 children per day. The mean age of children at health facilities was 2.2 years (SD 2.8); it did not differ by sex. Children at North-central region facilities were younger than children at North-west region facilities (1.8 years versus 6.6 years, P < 0.001). Conclusions: While many children attend local health facilities, confirming feasibility of obtaining controls, their mean age is much lower than BL cases. Health facilities may be suitable for obtaining young, but not older, controls.
The Challenge of HIV-1 Antiretroviral Resistance in Africa in the Era of HAART
(AIDS reviews, 2009) Sendagire, Hakim; Easterbrook, Philippa J.; Nankya, Immaculate; Arts, Eric; Thomas, David; Reynolds, Steven J.
Antiretroviral therapy programs in Africa are currently providing treatment for almost two million people. The long-term success of large scale antiretroviral therapy programs in sub-Saharan Africa remains uncertain because of the limited information currently available on rates of virologic failure and selection for drug-resistant variants in the different HIV subtypes. This article provides a comprehensive review of the published literature on the prevalence of primary and secondary HIV drug resistance with different subtypes and in various settings across sub-Saharan Africa.
Dynamics Of Pre-Exposure (PrEP) Eligibility due to Waxing and Waning of HIV Risk in Rakai, Uganda
(JAIDS Journal of Acquired Immune Deficiency Syndromes, 2022) Ssempijja, Victor; Ssekubugu, Robert; Kigozi, Godfrey; Nakigozi, Gertrude; Kagaayi, Joseph; Nalugoda, Fred; Nantume, Betty; Batte, James; Kigozi, Grace; Nakawooya, Hadijja; Serwadda, David; Reynolds, Steven J.
We conducted a retrospective population-based study to describe longitudinal patterns of prevalence, incidence, discontinuation, resumption, and durability of substantial HIV risk behaviors (SHR) for PrEP eligibility.The study was conducted among HIV-negative study participants aged 15-49 years that participated in survey rounds of the Rakai Community Cohort Study between August 2011 and June 2018. SHR was defined based on the Uganda national PrEP eligibility as either reporting sexual intercourse with >1 partner of unknown HIV status, non-marital sex without a condom or having transactional sex. Resumption of SHR meant resuming of SHR after stopping SHR, while persistence of SHR meant SHR on >1 consecutive visit. We used generalized estimation equations (GEE) with log-binomial regression models and robust variance to estimate survey-specific prevalence ratios (PR); GEE with modified Poisson regression models and robust variance to estimate incidence ratios for incidence, discontinuation, and resumption of PrEP eligibility.PrEP use should be tailored to the dynamic nature of PrEP eligibility. Preventive-effective adherence should be adopted for assessment of attrition in PrEP programs.
The Effect of Antiretroviral Therapy Initiation on the Vaginal Microbiome in HIV-Infected Women
(The Journal of infectious diseases, 2021) Liu, Cindy M.; Packman, Zoe R.; Abraham, Alison G.; Serwadda, David M.; Nalugoda, Fred; Aziz, Maliha; Prodger, Jessica L.; Kaul, Rupert; Kalibbala, Sarah; Gray, Ronald H.; Price, Lance B.; Quinn, Thomas C.; Tobian, Aaron A.R.; Reynolds, Steven J.
The impact of antiretroviral therapy (ART) initiation on the vaginal microbiome is unknown. This is of particular importance among women living in sub-Saharan Africa. Understanding this relationship could help elucidate if and how the host immune system interacts with the vaginal microbiome. Methods. The vaginal microbiome of HIV-1/HSV-2-coinfected women (n = 92) in Uganda was evaluated from self-collected vaginal swabs 1 month pre-ART and at 4 and 6 months post–ART initiation. The vaginal microbiome was characterized by 16S rRNA genebased sequencing and quantitative polymerase chain reaction. Vaginal community state types (CSTs) were identified using proportional abundance data. Changes in microbiome composition were assessed with permutational analyses of variance (PerMANOVA).
Effect of Peer Health Workers on AIDS Care in Rakai, Uganda: A Cluster-Randomized Trial
(PloS one, 2010) Chang, Larry W.; Kagaayi, Joseph; Nakigozi, Gertrude; Ssempijja, Victor; Packer, Arnold H.; Serwadda, David; Quinn, Thomas C.; Gray, Ronald H.; Bollinger, Robert C.; Reynolds, Steven J.
Human resource limitations are a challenge to the delivery of antiretroviral therapy (ART) in low-resource settings. We conducted a cluster randomized trial to assess the effect of community-based peer health workers (PHW) on AIDS care of adults in Rakai, Uganda. Methodology/Principal Findings: 15 AIDS clinics were randomized 2:1 to receive the PHW intervention (n = 10) or control (n = 5). PHWtasks included clinic and home-based provision of counseling, clinical, adherence to ART, and social support. Primary outcomes were adherence and cumulative risk of virologic failure (.400 copies/mL). Secondary outcomes were virologic failure at each 24 week time point up to 192 weeks of ART. Analysis was by intention to treat. FromMay 2006 to July 2008, 1336 patients were followed. 444 (33%) of these patients were already on ART at the start of the study. No significant differences were found in lack of adherence (,95% pill count adherence risk ratio [RR] 0.55, 95% confidence interval [CI] 0.23–1.35; ,100% adherence RR 1.10, 95% CI 0.94–1.30), cumulative risk of virologic failure (RR 0.81, 95% CI 0.61–1.08) or in shorter-term virologic outcomes (24 week virologic failure RR 0.93, 95% CI 0.65–1.32; 48 week, RR 0.83, 95% CI 0.47–1.48; 72 week, RR 0.81, 95% CI 0.44–1.49). However, virologic failure rates$96 weeks into ART were significantly decreased in the intervention armcompared to the control arm (96 week failure RR 0.50, 95% CI 0.31–0.81; 120 week, RR 0.59, 95% CI 0.22–1.60; 144 week, RR 0.39, 95% CI 0.16–0.95; 168 week, RR 0.30, 95% CI 0.097–0.92; 192 week, RR 0.067, 95% CI 0.0065–0.71). Conclusions/Significance: A PHW intervention was associated with decreased virologic failure rates occurring 96 weeks and longer into ART, but did not affect cumulative risk of virologic failure, adherence measures, or shorter-term virologic outcomes. PHWs may be an effective intervention to sustain long-term ART in low-resource settings
Effectiveness of Voluntary Medical Male Circumcision for Human Immunodeficiency Virus Prevention in Rakai, Uganda
(Clinical Infectious Diseases, 2021) Loevinsohn, Gideon; Kigozi, Godfrey; Kagaayi, Joseph; Wawer, Maria J.; Nalugoda, Fred; Chang, Larry W.; Quinn, Thomas C.; Serwadda, David; Reynolds, Steven J.; Nelson, Lisa; Mills, Lisa; Alamo, Stella; Nakigozi, Gertrude; Kabuye, Geoffrey; Ssekubugu, Robert; Tobian, Aaron A. R.; Gray, Ronald H.; Grabowski, M. Kathryn
The efficacy of voluntary male medical circumcision (VMMC) for human immunodeficiency virus (HIV) prevention in men was demonstrated in 3 randomized trials. This led to the adoption of VMMC as an integral component of the United States President’s Emergency Plan for AIDS Relief (PEPFAR) combination HIV prevention program in sub-Saharan Africa. However, evidence on the individual-level effectiveness of VMMC programs in real-world, programmatic settings is limited. A cohort of initially uncircumcised, non-Muslim, HIV-uninfected men in the Rakai Community Cohort Study in Uganda was followed between 2009 and 2016 during VMMC scale-up. Self-reported VMMC status was collected and HIV tests performed at surveys conducted every 18 months. Multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) of HIV acquisition in newly circumcised vs uncircumcised men.
Evaluation of current rapid HIV test algorithms in Rakai, Uganda
(Journal of virological methods, 2013) Galiwango, Ronald M.; Musoke, Richard; Lubyayi, Lawrence; Ssekubugu, Robert; Kalibbala, Sarah; Ssekweyama, Viola; Mirembe, Viola; Nakigozi, Gertrude; Reynolds, Steven J.; Serwadda, David; Gray, Ronald H.; Kigozi, Godfrey
Rapid HIV tests are a crucial component of HIV diagnosis in resource limited settings. In Uganda, the Ministry of Health allows for both serial and parallel HIV rapid testing using Determine, Stat- Pak and Uni-Gold. In serial testing, a non-reactive result on Determine ends testing. The performance of serial and parallel algorithms with Determine and Stat-Pak test kits was assessed. A cross-sectional diagnostic test accuracy evaluation using three rapid HIV test kits as per the recommended parallel test algorithm was followed by EIA-WB testing with estimates of the performance of serial testing algorithm. In 2520 participants tested by parallel rapid algorithms, 0.6% had weakly reactive result. Parallel testing had 99.7% sensitivity and 99.8% specificity. If Stat-Pak was used as the first screening test for a serial algorithm, the sensitivity was 99.6% and specificity 99.7%. However, if Determine was used as the screening test, sensitivity was 97.3% and specificity 99.9%. Serial testing with Stat-Pak as the initial screening test performed as well as parallel testing, but Determine was a less sensitive screen. Serial testing could be cost saving.
Failure of immunologic criteria to appropriately identify antiretroviral treatment failure in Uganda
(AIDS, 2009) Reynolds, Steven J.; Nakigozi, Gertrude; Newell, Kevin; Ndyanabo, Anthony; Galiwongo, Ronald; Iga, Boaz; Quinn, Thomas C.; Gray, Ron; Wawer, Maria; Serwadda, David
Most antiretroviral treatment program in resource-limited settings use immunologic or clinical monitoring to measure response to therapy and to decide when to change to a second line regimen. Our objective was to evaluate immunologic failure criteria against gold standard virologic monitoring. Design—Observation cohort Methods—Participants enrolled in an antiretroviral treatment program in rural Uganda who had at least 6 months of follow-up were included in this analysis. Immunologic monitoring was performed by CD4 cell counts every 3 months during the first year, and every 6 months thereafter. HIV-1 viral loads were performed every 6 months. Results—1133 participants enrolled in the Rakai Health Sciences Program antiretroviral treatment program between June 2004 and September 2007 were followed for up to 44.4 months (median follow-up 20.2 months; IQR 12.4–29.5 months). WHO immunologic failure criteria were reached by 125 (11.0%) participants. A virologic failure endpoint defined as HIV-1 viral load (VL) >400 copies/ml on two measurements was reached by 112 participants (9.9%). Only 26 participants (2.3%) experienced
Failure of immunologic criteria to appropriately identify antiretroviral treatment failure in Uganda
(AIDS (London, England), 2009-03) Reynolds, Steven J.; Nakigozi, Gertrude; Newell, Kevin; Ndyanabo, Anthony; Ronald, Galiwongo; Iga, Boaz; . Quinn, Thomas C; Gray, Ron; Wawer, Maria; Serwadda, David
Objective—Most antiretroviral treatment program in resource-limited settings use immunologic or clinical monitoring to measure response to therapy and to decide when to change to a second line regimen. Our objective was to evaluate immunologic failure criteria against gold standard virologic monitoring. Design—Observation cohort Methods—Participants enrolled in an antiretroviral treatment program in rural Uganda who had at least 6 months of follow-up were included in this analysis. Immunologic monitoring was performed by CD4 cell counts every 3 months during the first year, and every 6 months thereafter. HIV-1 viral loads were performed every 6 months. Results—1133 participants enrolled in the Rakai Health Sciences Program antiretroviral treatment program between June 2004 and September 2007 were followed for up to 44.4 months (median follow-up 20.2 months; IQR 12.4–29.5 months). WHO immunologic failure criteria were reached by 125 (11.0%) participants. A virologic failure endpoint defined as HIV-1 viral load (VL) >400 copies/ml on two measurements was reached by 112 participants (9.9%). Only 26 participants (2.3%) experienced both an immunologic and virologic failure endpoint (2 VL>400 copies/ml) during follow-up. Conclusions—Immunologic failure criteria performed poorly in our setting and would have resulted in a substantial proportion of participants with suppressed HIV-1 VL being switched unnecessarily. These criteria also lacked sensitivity to identify participants failing virologically. Periodic viral load measurements may be a better marker for treatment failure in our setting
Hepatitis B virus and sexual behavior in Rakai, Uganda
(Journal of medical virology, 2011) Stabinski, Lara; Reynolds, Steven J.; Ocama, Ponsiano; Laeyendecker, Oliver; Serwadda, David; Gray, Ron H.; Wawer, Maria; Thomas, David L.; Quinn, Thomas C.; Kirk, Gregory D.
HIV and hepatitis B virus (HBV) co-infection poses important public health considerations in resource-limited settings. Demographic data and sera from adult participants of the Rakai Health Sciences Program Cohort in Southwestern Uganda were examined to determine HBV seroprevalence patterns in this area of high HIV endemicity prior to the introduction of antiretroviral therapy. Commercially available EIAs were used to detect prevalent HBV infection (positive for HBV core antibody [anti-HBc] and/or positive HBV surface antigen [HBsAg]), and chronic infection (positive for HBsAg). Of 438 participants, 181 (41%) had prevalent HBV infection while 21 (5%) were infected chronically. Fourteen percent of participants were infected with HIV. Fifty three percent showed evidence of prevalent HBV infection compared to 40% among participants infected with HIV (p=0.067). Seven percent of participants infected with HIV were HBsAg positive compared to 4% among participants not infected with HIV (p=0.403). The prevalence of prevalent HBV infection was 55% in adults aged >50 years old, and 11% in persons under 20 years. In multivariable analysis, older age, HIV status and serologic syphilis were significantly associated with prevalent HBV infection. Transfusion status and receipt of injections were not significantly associated with HBV infection. Contrary to expectations that HBV exposure in Uganda occurred chiefly during childhood, prevalent HBV infection was found to increase with age and was associated sexually transmitted diseases (HIV and syphilis.) Therefore vaccination against HBV, particularly susceptible adults with HIV or at risk of HIV/STDs should be a priority.
Hepatitis E Virus Seroprevalence and Correlates of Anti-HEV IgG Antibodies in the Rakai District, Uganda
(The Journal of Infectious Diseases, 2018) Boon, Denali; Redd, Andrew D.; Laeyendecker, Oliver; Engle, Ronald E.; Nguyen, Hanh; Ocama, Ponsiano; Boaz, Iga; Ndyanabo, Anthony; Kiggundu, Valerian; Reynolds, Steven J.; Gray, Ronald H.; Wawer, Maria J.; Purcell, Robert H.; Kirk, Gregory D.; Quinn, Thomas C.; Stabinski, Lara
A cross-sectional study was conducted of 500 human immunodeficiency virus (HIV)-infected adults frequency matched on age, sex, and community to 500 HIV-uninfected individuals in the Rakai District, Uganda to evaluate seroprevalence of anti-hepatitis E virus (HEV) IgG antibodies. HEV seroprevalence was 47%, and 1 HIV-infected individual was actively infected with a genotype 3 virus. Using modified Poisson regression, male sex (prevalence ratios [PR] = 1.247; 95% confidence interval [CI], 1.071–1.450) and chronic hepatitis B virus infection (PR = 1.377; 95% CI, 1.090–1.738) were associated with HEV seroprevalence. HIV infection status (PR = 0.973; 95% CI, 0.852–1.111) was not associated with HEV seroprevalence. These data suggest there is a large burden of prior exposure to HEV in rural Uganda.
Heterogeneity of the HIV epidemic in agrarian, trading, and fi shing communities in Rakai, Uganda: an observational epidemiological study
(The lancet HIV, 2016) Chang, Larry W.; Grabowsk, Mary K.; Ssekubugu, Robert; Nalugoda, Fred; Kigozi, Godfrey; Nantume, Betty; Lessler, Justin; Moore, Sean M.; Quinn, Thomas C.; Reynolds, Steven J.; Gray, Ronald H.; Serwadda, David; Wawer, Maria J.
Understanding the extent to which HIV burden diff ers across communities and the drivers of lo cal disparities is crucial for an eff ective and targeted HIV response. We assessed community-level variations in HIV prevalence, risk factors, and treatment and prevention service uptake in Rakai, Uganda. Methods The Rakai Community Cohort Study (RCCS) is an open, population-based cohort of people aged 15–49 years in 40 communities. Participants are HIV tested and interviewed to obtain sociodemographic, behavioural, and health information. RCCS data from Aug 10, 2011, to May 30, 2013, were used to classify communities as agrarian (n=27), trading (n=9), or lakeside fi shing sites (n=4). We mapped HIV prevalence with Bayesian methods, and characterised variability across and within community classifi cations. We also assessed diff erences in HIV risk factors and uptake of antiretroviral therapy and male circumcision between community types. Findings 17 119 individuals were included, 9215 (54%) of whom were female. 9931 participants resided in agrarian, 3318 in trading, and 3870 in fi shing communities. Median HIV prevalence was higher in fi shing communities (42%, range 38–43) than in trading (17%, 11–21) and agrarian communities (14%, 9–26). Antiretroviral therapy use was signifi cantly lower in both men and women in fi shing communities than in trading (age-adjusted prevalence risk ratio in men 0·64, 95% CI 0·44–0·97; women 0·53, 0·42–0·66) and agrarian communities (men 0·55, 0·42–0·72; women 0·65, 0·54–0·79), as was circumcision coverage among men (vs trading 0·48, 0·42–0·55; vs agrarian 0·64, 0·56–0·72). Self-reported risk behaviours were signifi cantly higher in men than in women and in fi shing communities than in other community types. Interpretation Substantial heterogeneity in HIV prevalence, risk factors, and service uptake in Rakai, Uganda, emphasises the need for local surveillance and the design of targeted HIV responses. High HIV burden, risk behaviours, and low use of combination HIV prevention in fi shing communities make these populations a priority for intervention. Funding National Institute of Mental Health, the National Institute of Allergy and Infectious Diseases, the National Institute of Child Health and Development, and the National Institute for Allergy and Infectious Diseases Division of Intramural Research, National Institutes of Health; the Bill & Melinda Gates Foundation; and the Johns Hopkins University Center for AIDS Research.
High Frequency of False-Positive Hepatitis C Virus Enzyme-Linked Immunosorbent Assay in Rakai, Uganda
(Clinical infectious diseases, 2013) Mullis, Caroline E.; Laeyendecker, Oliver; Reynolds, Steven J.; Ocama, Ponsiano; Quinn, Jeffrey; Boaz, Iga; Gray, Ronald H.; Kirk, Gregory D.; Thomas, David L.; Quinn, Thomas C.; Stabinski, Lara
The prevalence of hepatitis C virus (HCV) infection in sub- Saharan Africa remains unclear. We tested 1000 individuals from Rakai, Uganda, with the Ortho version 3.0 HCV enzyme-linked immunosorbent assay. All serologically positive samples were tested for HCV RNA. Seventy-six of the 1000 (7.6%) participants were HCV antibody positive; none were confirmed by detection of HCV RNA.
High Rates of Pre-exposure Prophylaxis Eligibility and Associated HIV Incidence in a Population With a Generalized HIV Epidemic in Rakai, Uganda
(Journal of Acquired Immune Deficiency Syndromes, 2022) Ssempijja, Victor; Nakigozi, Gertrude; Ssekubugu, Robert; Kagaayi, Joseph; Kigozi, Godfrey; Nalugoda, Fred; Nantume, Betty; Batte, James; Kigozi, Grace; Nakawooya, Hadijja; Serwadda, David; Cobelens, Frank; Reynolds, Steven J.
The utility of using pre-exposure prophylaxis (PrEP) eligibility assessments to identify eligibility in general populations has not been well studied in sub-Saharan Africa. We used the Rakai Community Cohort Study to conduct a cross-sectional analysis to estimate PrEP eligibility and a cohort analysis to estimate HIV incidence associated with PrEP eligibility. Based on Uganda's national PrEP eligibility tool, we defined eligibility as reporting at least one of the following HIV risks in the past 12 months: sexual intercourse with more than one partner of unknown HIV status; nonmarital sex act without a condom; sex engagement in exchange for money, goods, or services; or experiencing genital ulcers. We used log-binomial and modified Poisson models to estimate prevalence ratios for PrEP eligibility and HIV incidence, respectively.
HIV Infection in Uncircumcised Men is Associated with Altered CD8 T-cell Function but Normal CD4 T-cell Numbers in the Foreskin
(The Journal of infectious diseases, 2014) Prodger, Jessica L.; Hirbod, Taha; Gray, Ronald; Kigozi, Godfrey; Nalugoda, Fred; Galiwango, Ronald; Reynolds, Steven J.; Huibner, Sanja; Wawer, Maria J.; Serwadda, David; Kaul, Rupert; Rakai, Genital Immunology Research Group
Human immunodeficiency virus (HIV)–infected (HIV+) men are more susceptible to sexually transmitted infections, and may be superinfected by HIV. We hypothesized that HIV induces immune alterations in the foreskin that may impact the subsequent acquisition/clearance of genital coinfections. Methods. Foreskin tissue and blood were obtained from 70 HIV-uninfected and 20 HIV+ men undergoing circumcision. T cells were characterized by flow cytometry, immunohistochemistry, and polymerase chain reaction. Results. There was substantial influx of CD8 T-cells into the foreskins of HIV+ men (108.8 vs 23.1 cells/mm2; P < .001); but foreskin CD4 T-cell density was unchanged (43.0 vs 33.7/mm2; P = .67), despite substantial blood depletion (409.0 vs 877.8 cells/μL; P < .001). While frequencies of foreskin C-C chemokine receptor type 5+ (CCR5+) T cells, T regulatory cells, and T-helper 17 cells were unaltered in HIV+ men, CD8 T-cell production of tumor necrosis factor α (TNFα) was decreased. HIV-specific CD8 T cells were present in the foreskins of HIV+ men, although their frequency and function was reduced compared to the blood. Conclusions. Foreskin CD4 T-cell density and CCR5 expression were not reduced during HIV infection, perhaps explaining susceptibility to HIV superinfection. Foreskin CD8 T-cell density was increased, but decreased production of TNFα may enhance susceptibility to genital coinfections in HIV+ men.
HIV serologically indeterminate individuals: Future HIV status and risk factors
(PLoS ONE, 2020) Mwinnyaa, George; Grabowski, Mary K.; Gray, Ronald H.; Wawer, Maria; Chang, Larry W.; Ssekasanvu, Joseph; Kagaayi, Joseph; Kigozi, Godfrey; Kalibbala, Sarah; Galiwango, Ronald M.; Ndyanabo, Anthony; Serwadda, David; Quinn, Thomas C.; Reynolds, Steven J.; Laeyendecker, Oliver
Indeterminate HIV test results are common, but little is known about the evolution of indeterminate serology and itssociodemographic and behavioral correlates. We assessed future HIV serological outcomes for individuals with indeterminate results and associated factors in Rakai, Uganda. Methods 115,944 serological results, defined by two enzyme immunoassay (EIAs), among 39,440 individuals aged 15–49 years in the Rakai Community Cohort Study were assessed. Indeterminate results were defined as contradictory EIAs. Modified Poisson regression models with generalized estimating equations were used to assess prevalence ratios (PRs) of subsequent HIV serological outcomes and factors associated with HIV indeterminate results.

Browsing by Author "Reynolds, Steven J."

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