Browsing by Author "Gray, Ronald"
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Item 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.Item Assessment of Changes in Risk Behaviors During 3 Years of Posttrial Follow-up of Male Circumcision Trial Participants Uncircumcised at Trial Closure in Rakai, Uganda(American journal of epidemiology, 2012) Kong, Xiangrong; Kigozi, Godfrey; Nalugoda, Fred; Musoke, Richard; Kagaayi, Joseph; Latkin, Carl; Ssekubugu, Robert; Lutalo, Tom; Nantume, Betty; Iga, Boaz; Wawer, Maria; Serwadda, David; Gray, RonaldRisk compensation associated with male circumcision has been a concern for male circumcision scale-up programs. Using posttrial data collected during 2007–2011 on 2,137 male circumcision trial participants who were uncircumcised at trial closure in Rakai, Uganda, the authors evaluated their sexual behavioral changes during approximately 3 years’ follow-up after trial closure. Eighty-one percent of the men self-selected for male circumcision during the period, and their sociodemographic and risk profiles were comparable to those of men remaining uncircumcised. Linear models for marginal probabilities of repeated outcomes estimate that 3.3% (P < 0.0001) of the male circumcision acceptors reduced their engagement in nonmarital relations, whereas there was no significant change among men remaining uncircumcised. Significant decreases in condom use occurred in both male circumcision acceptors (−9.2% with all partners and −7.0% with nonmarital partners) and nonacceptors (−12.4% and −13.5%, respectively), and these were predominantly among younger men. However, the magnitudes of decrease in condom use were not significantly different between the 2 groups. Additionally, significant decreases in sex-related alcohol consumption were observed in both groups (−7.8% in male circumcision acceptors and −6.1% in nonacceptors), mainly among older men. In summary, there was no evidence of risk compensation associated with male circumcision among this cohort of men during 3 years of posttrial follow-up.Item Coercive sex in rural Uganda: Prevalence and associated risk factors(Social Science & Medicine, 2004) Koenig, Michael A.; Lutalo, Tom; Zhao, Feng; Nalugoda, Fred; Kiwanuka, Noah; Wabwire-Mangen, Fred; Kigozi, Godfrey; Sewankambo, Nelson; Wagman, Jennifer; Serwadda, David; Wawer, Maria; Gray, RonaldDespite growing recognition of the problem, relatively little is known about the issue of coercive sex in developing countries. This study presents findings from a community-based survey of 4279 reproductive-aged women in current partnerships in the Rakai District of Uganda carried out in 1998–99. One in four women in our study report having experienced coercive sex with their current male partner, with most women reporting its occasional occurrence. In a regression analysis of risk factors for coercive sex, conventional socio-demographic characteristics emerged as largely unpredictive of the risk of coercive sex. Behavioral risk factors—most notably, younger age of women at first intercourse and alcohol consumption before sex by the male partner—were strongly and positively related to the risk of coercive sex. Coercive sex was also strongly related to perceptions of the male partner’s HIV risk, with women who perceived their partner to be at highest risk experiencing almost three times the risk of coercive sex relative to low risk partnerships. Supplemental analysis of 1-year longitudinal data provides additional support for the hypothesis that coercive sex may frequently be a consequence of women’s perceptions of increased HIV risk for their male partner. The findings of this study are discussed in terms of the need for sexual violence prevention programs more generally in settings such as Uganda, and in terms of the possible importance of incorporating issues of sexual and physical violence within current HIV prevention programs.Item Domestic violence in rural Uganda: evidence from a community-based study(Bulletin of the world health organization, 2003) Koenig, Michael A.; Lutalo, Tom; Zhao, Feng; Nalugoda, Fred; Wabwire-Mangen, Fred; Kiwanuka, Noah; Wagman, Jennifer; Serwadda, David; Wawer, Maria; Gray, RonaldAlthough domestic violence is an increasing public health concern in developing countries, evidence from representative, community-based studies is limited. In a survey of 5109 women of reproductive age in the Rakai District of Uganda, 30% of women had experienced physical threats or physical abuse from their current partner—20% during the year before the survey. Three of five women who reported recent physical threats or abuse reported three or more specific acts of violence during the preceding year, and just under a half reported injuries as a result. Analysis of risk factors highlights the pivotal roles of the male partner’s alcohol consumption and his perceived human immunodeficiency virus (HIV) risk in increasing the risk of male against female domestic violence. Most respondents —70% of men and 90% of women—viewed beating of the wife or female partner as justifiable in some circumstances, posing a central challenge to preventing violence in such settings.Item Elevated liver stiffness without histological evidence of liver fibrosis in rural Ugandans(J Viral Hepat, 2019) Tibuakuu, Martin; Jjingo, Caroline; Dale Kirk, Gregory; Thomas, David Lee; Gray, Ronald; Ssempijja, Victor; Nalugoda, Fred; Serwadda, David; Ocama, Ponsiano; Opio, Christopher Kenneth; Kleiner, David Erwin; Charles Quinn, Thomas; Reynolds, Steven JamesLiver fibrosis may be assessed noninvasively with transient electrography (TE). Data on the performance of TE for detecting liver fibrosis in sub-Saharan Africa are limited. We evaluated the diagnostic accuracy of TE by performing liver biopsies on persons with liver fibrosis indicated by TE. We enrolled HIV-infected and HIV-uninfected participants with TE scores consistent with at least minimal disease (liver stiffness measurement [LSM]≥7.1 kPa). Biopsies were performed and staged using the Ishak scoring system. A concordant result was defined using accepted thresholds for significant fibrosis by TE (LSM ≥ 9.3 kPa) and liver biopsy (Ishak score ≥ 2). We used modified Poisson regression methods to quantify the univariate and adjusted prevalence risk ratios (PRR) of the association between covariates and the concordance status of TE and liver biopsy in defining the presence of liver fibrosis. Of 131 participants with valid liver biopsy and TE data, only 5 participants (3.8%) had Ishak score ≥ 2 of whom 4 had LSM ≥ 9.3 kPa (sensitivity = 80%); of the 126 (96.2%) with Ishak score < 2, 76 had LSM < 9.3 kPa (specificity = 61%). In multivariable analysis, discordance was associated with female gender (adjPRR = 1.80, 95%CI 1.1-2.9; P = .019), herbal medicine use (adjPRR 1.64, 95% CI = 1.0-2.5; P = .022), exposure to lake or river water (adjPRR 2.05, 95% CI = 1.1-3.7; P = .016), and current smoking (adjPRR 1.72, 95%CI 1.0-2.9; P = .045). These data suggest that TE among rural Ugandans has low specificity for detection of histologically confirmed liver fibrosis. Caution should be exercised when using this tool to confirm significant liver fibrosis.Item 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 GroupHuman 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.Item Knowledge on Voluntary Medical Male Circumcision in a Low uptake Setting in Northern Uganda(BMC public health, 2018) Nanteza, Barbara Marjorie; Serwadda, David; Kankaka, Edward Nelson; Mongo, Grace Bua; Gray, Ronald; Makumbi, Frederick EdwardFree VMMC services have been available in Uganda since 2010. However, uptake in Northern Uganda remains disproportionately low. We aimed to determine if this is due to men’s insufficient knowledge on VMMC, and if women’s knowledge on VMMC has any association with VMMC status of their male sexual partners.Item Mortality in HIV-Infected and Uninfected Children of HIV-Infected and Uninfected Mothers in Rural Uganda(JAIDS Journal of Acquired Immune Deficiency Syndromes, 2006) Brahmbhatt, Heena; Kigozi, Godfrey; Wabwire-Mangen, Fred; Lutalo, Tom; Serwadda, David; Nalugoda, Fred; Sewankambo, Nelson; Kiduggavu, Mohamed; Wawer, Maria J.; Gray, RonaldTo estimate 2-year mortality rates in HIV-1Yinfected and uninfected infants born to HIV+ and HIVj mothers. Methods: Data are from a prospective study in rural Rakai District, Uganda. Infant HIV status (determined by polymerase chain reaction) was evaluated at 1 to 6 weeks postpartum and during breastfeeding, and maternal HIV viral load and CD4 levels were measured at the postpartum visit. Multivariate Cox proportional hazards models and Kaplan-Meier survival analysis were used to assess survival of infants by maternal and infant HIV status and by quartiles of viral load. Log-rank tests were used to test the equality of survival functions. Results: Of the 4604 pregnant women, 16.9% were HIV+, and the proportion of children infected was 20.9%. Median survival of HIV-infected infants was 23 months. Two-year child mortality rates were 128 of 1000 children born to HIVj mothers, 165.5 of 1000 uninfected children born to HIV+ mothers, and 540.1 of 1000 HIVinfected children (P G 0.0001). Compared with children of HIVj mothers, the hazard of child mortality was 2.04 (P G 0.001) if the mother was HIV+and 3.78 (P G 0.001) if the infant was also infected. In the adjusted model, the highest quartiles of log10 HIV viral load in infants and mothers were associated with significantly increased hazard of child mortality (hazard ratio [HR] = 8.54 and HR = 2.50, respectively). Maternal CD4 counts G200 cells/mL were also significant predictors of child mortality (HR = 2.61). A total of 67.6% of HIV-infected children with viral loads above the median died by the age of 2 years and are in need of early antiretroviral therapy (ART).Item Personal and community benefits and harms of research: views from Rakai, Uganda(Aids, 2007) Thiessena, Carrie; Ssekubugu, Robert; Wagman, Jennifer; Kiddugavu, Mohammed; Wawer, Maria J.; Emanuel, Ezekiel; Gray, Ronald; Serwadda, David; Grady, ChristineTo assess what individuals in low-income countries perceive as benefits and harms of population-based HIV/STD research. Design: A total of 811 research participants, research decliners, and community opinion leaders in the Rakai District, Uganda were surveyed. Types of personal and community benefits and harms, as well as rates of reporting great personal and community benefit were assessed. Methods: Using logistic regression, demographic characteristics, participant and opinion leader status, use of Rakai Health Sciences Program (RHSP) services, and perceived research effects were entered as predictors of reported great personal and great community benefit. Results: Most respondents thought that RHSP research was of great personal (85%) and community (88%) benefit. The perception that the RHSP was a great personal benefit was correlated with female sex, post-secondary education, frequent use of RHSPsponsored medical services, health knowledge gains, and increased hope for future health improvements. Persons of non-Baganda ethnicity and 30–39 year-olds were less likely to believe research was personally beneficial. Regarding research as a great community benefit was associated with reported health knowledge gains, greater hope for Rakai residents’ future health, and local economic benefit. Decliners were the most likely to report a personal harm, while community opinion leaders identified community harms at the highest rates. Conclusions: The majority of Rakai residents report that HIV/STD research has enhanced their own and their communities’ welfare. Different factors were associated with the belief that research is a personal versus community benefit. Variations in participant, decliner, and community opinion leader perceptions highlight inadequacies of current community consultation mechanisms.Item Prevalence Of Protective Tetanus Antibodies And Immunological Response Following Tetanus Toxoid Vaccination Among Men Seeking Medical Circumcision Services In Uganda(PloS one, 2018) Makumbi, Fredrick; Byabagambi, John; Muwanika, Richard; Kigozi, Godfrey; Gray, Ronald; Galukande, Moses; Bagaya, Bernard; Ssebagala, Darix; Karamagi, Esther; Rahimzai, Mirwais; Kaggwa, Mugagga; Watya, Stephen; Mbonye, Anthony K.; Aceng, Jane Ruth; Musinguzi, Joshua; Kiggundu, Valerian; Njeuhmeli, Emmanuel; Nanteza, BarbaraTetanus infection associated with men who had male circumcision has been reported in East Africa, suggesting a need for tetanus toxoid-containing vaccines (TTCV).To determine the prevalence of tetanus toxoid antibodies following vaccination among men seeking circumcision. We enrolled 620 consenting men who completed a questionnaire and received TTCV at enrollment (day 0) prior to circumcision on day 28. Blood samples were obtained at day 0 from all enrollees and on days 14, 28 and 42 from a random sample of 237 participants. Tetanus toxoid (TT) IgG antibody levels were assayed using EUROIMMUN. Analyses included prevalence of TT antibodies at enrollment and used a mixed effects model to determine the immunological response.Mean age was 21.4 years, 65.2% had knowledge of tetanus, 56.6% knew how tetanus was contracted, 22.8% reported ever receipt of TTCV, and 16.8% had current/recently healed wounds. Insufficient tetanus immunity was 57.1% at enrollment, 7.2% at day 14, 3.8% at day 28, and 0% at day 42. Antibody concentration was 0.44IU/ml (CI 0.35–0.53) on day 0, 3.86IU/ml (CI 3.60–4.11) on day 14, 4.05IU/ml (CI 3.81–4.29) on day 28, and 4.48IU/ml (CI 4.28–4.68) on day 42. TT antibodies increased by 0.24IU/ml (CI 0.23, 0.26) between days 0 and 14 and by 0.023IU/ml (CI 0.015, 0.031) between days 14 and 42 days. Immunological response was poorer in HIV-infected clients and men aged 35+ years.Insufficient immunity was common prior to TTCV, and a protective immunological response was achieved by day 14. Circumcision may safely be provided 14 days after vaccination in HIV-uninfected men aged less than 35 years.Item Severe Acute Respiratory Syndrome Coronavirus-2 Seropositivity in South-Central Uganda, During 2019 - 2021(Research Square, 2021) Ssuuna, Charles; Galiwango, Ronald Moses; Kankaka, Edward Nelson; Kagaayi, Joseph; Ndyanabo, Anthony; Kigozi, Godfrey; Nakigozi, Gertrude; Lutalo, Tom; Ssekubugu, Robert; Wasswa, John Bosco; Mayinja, Anthony; Nakibuuka, Martina Cathy; Jamiru, Samiri; Oketch, John Baptist; Muwanga, Edward; Chang, Larry William; Grabowski, Mary Kate; Wawer, Maria; Gray, Ronald; Anderson, Mark; Serwadda, DavidGlobally, key subpopulations such as healthcare workers (HCWs) have a higher risk of contracting SARS-CoV-2. In Uganda, limited access to personal protective equipment amidst lack of clarity on the extent and pattern of the community disease burden may exacerbate this situation. We assessed SARS-CoV-2 antibody seroprevalence among high-risk sub-populations in South-central Uganda, including HCWs, persons within the general population previously reporting experiencing key COVID-19 like symptoms (fever, cough, loss of taste and smell) and archived plasma specimens collected between October 2019 – 18th March 2020, prior to confirmation of COVID-19 in Uganda.Item Use of a mixture of lignocaine and bupivacaine vs lignocaine alone for male circumcision under local anaesthesia in Rakai, Uganda(BJU international, 2012) Kigozi, Godfrey; Musoke, Richard; Anyokorit, Margaret; Nkale, James; Kighoma, Nehemiah; Ssebanenya, William; Mwinike, Joshua; Watya, Stephen; Nalugoda, Fred; Kagaayi, Joseph; Nalwoga, Grace; Nakigozi, Gertrude; Kiwanuka, Noah; Makumbi, Frederick; Lutalo, Tom; Serwadda, David; Wawer, Maria; Gray, RonaldMale circumcision (MC) has been shown to reduce the risk of HIV acquisition by 50 – 60% [ 1 – 3 ] and the WHO now recommends it as one of the proven methods for HIV prevention [ 4 ] . Several programmes in sub-Saharan Africa have initiated MC implementation. For MC to be effective at a community level there is need to achieve high MC coverage, and modelling suggests that the higher the prevalence of MC the greater the impact on HIV incidence [ 5 ] . One reason consistently cited by men for not accepting MC is fear of pain during surgery [ 6 – 10 ] . Our experience in Rakai is that when men are offered MC, only a few men initially come for surgery, and the majority, fearing pain, wait to hear the experiences of men who have had surgery.