Browsing by Author "Laeyendecker, Oliver"
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Item Age-Disparate Relationships and HIV Prevalence among Never Married Women in Rakai, Uganda(Journal of acquired immune deficiency syndromes, 2018) Mwinnyaa, George; Gray, Ronald H.; Grabowski, Mary K.; Ssekasanvu, Joseph; Ndyanabo, Anthony; Ssekubugu, Robert; Kagaayi, Joseph; Kigozi, Godfrey; Nakigozi, Gertrude; Serwadda, David M.; Laeyendecker, OliverAge-disparate relationships are associated with increased HIV prevalence. We determined whether the frequency of age-disparate relationships in never married women changed over time and whether they are associated with HIV prevalence in Rakai, Uganda. Methods: 10,061 never married women, aged 15–49 in the Rakai Community Cohort Study provided information on the age of their male sexual partners from 1997 to 2013. Logistic regression was used to assess trends in age-disparate relationships (≥5 years) between never married women and their male partners. Log-binomial regression was used to estimate adjusted prevalence ratios (adjPR) of HIV prevalence associated with age-disparate relationships. Results: 2,992 women (30%) had a male partner ≥5 years older which remained stable over time. The prevalence of HIV among women in age-disparate relationships was 14%, 10% for women in relationships with men 0–4 years older (adjPR 1.36, 95% CI 1.22, 1.53) not controlling women’s age, however after age adjustment the impact of age-disparate relationships on HIV prevalence was attenuated. Age-disparate relationships were associated with increased HIV prevalence among women aged 15–17 (adjPR 1.83, 95% CI 1.10, 3.19), but not in other age groups. Conclusions: The frequency of age-disparate relationships among never married women were unchanged over a 15-year period in Rakai, Uganda. Age-disparate relationships were associated with increased HIV prevalence among adolescents 15–17, but not older women.Item 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.Item 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, LaraA 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.Item 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, LaraThe 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.Item 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, OliverIndeterminate 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.Item Inferring HIV-1 transmission networks and sources of epidemic spread in Africa with deep-sequence phylogenetic analysis(Nature communications, 2019) Ratmann, Oliver tophe Fraser; Grabowski, M. Kate; Hall, Matthew; Golubchik, Tanya; Wymant, Chris; Abeler-Dörner, Lucie; Bonsall, David; Hoppe, Anne; Leigh Brown, Andrew; Oliveira, Tulio de; Gall, Astrid; Kellam, Paul; Pillay, Deenan; Kagaayi, Joseph; Kigozi, Godfrey; Quinn, Thomas C.; Wawer, Maria J.; Laeyendecker, Oliver; Serwadda, David; Gray, Ronald H.To prevent new infections with human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa, UNAIDS recommends targeting interventions to populations that are at high risk of acquiring and passing on the virus. Yet it is often unclear who and where these ‘source’ populations are. Here we demonstrate how viral deep-sequencing can be used to reconstruct HIV-1 transmission networks and to infer the direction of transmission in these networks. We are able to deep-sequence virus from a large population-based sample of infected individuals in Rakai District, Uganda, reconstruct partial transmission networks, and infer the direction of transmission within them at an estimated error rate of 16.3% [8.8–28.3%]. With this error rate, deep-sequence phylogenetics cannot be used against individuals in legal contexts, but is sufficiently low for population-level inferences into the sources of epidemic spread. The technique presents new opportunities for characterizing source populations and for targeting of HIV-1 prevention interventions in Africa.Item Microbial translocation, the innate cytokine response, and HIV-1 disease progression in Africa(National Academy of Sciences, 2009) Redd, Andrew D.; Dabitao, Djeneba; Bream, Jay H.; Charvat, Blake; Laeyendecker, Oliver; Kiwanuka, Noah; Lutalo, Tom; Kigozi, Godfrey; Tobian, Aaron A. R.; Gamiel, Jordyn; Neal, Jessica D.; Oliver, Amy E.; Margolick, Joseph B.; Reynolds, Steven J.; Sewankambo, Nelson K.; Wawer, Maria J.; Serwadda, David; Gray, Ronald H.; Quinn, Thomas C.Reports from the United States have demonstrated that elevated markers of microbial translocation from the gut may be found in chronic and advanced HIV-1 infection and are associated with an increase in immune activation. However, this phenomenon’s role in HIV-1 disease in Africa is unknown. This study examined the longitudinal relationship between microbial translocation and circulating inflammatory cytokine responses in a cohort of people with varying rates of HIV-1 disease progression in Rakai, Uganda. Multiple markers for microbial translocation (lipopolysaccharide, endotoxin antibody, and sCD14) did not change significantly during HIV-1 disease progression. Moreover, circulating immunoreactive cytokine levels either decreased or remained virtually unchanged throughout disease progression. These data suggest that microbial translocation and its subsequent inflammatory immune response do not have a causal relationship with HIV-1 disease progression in Africa.Item Pregnancy Does Not Affect HIV Incidence Test Results Obtained Using the BED Capture Enzyme Immunoassay or an Antibody Avidity Assay(PLoS One, 2010) Laeyendecker, Oliver; Church, Jessica D.; Oliver, Amy E.; Mwatha, Anthony; Owen, S. Michele; Donnell, Deborah; Brookmeyer, Ron; Musoke, Philippa; Jackson, J. Brooks; Guay, Laura; Nakabiito, Clemesia; Quinn, Thomas C.; Eshleman, Susan H.Accurate incidence estimates are needed for surveillance of the HIV epidemic. HIV surveillance occurs at maternal-child health clinics, but it is not known if pregnancy affects HIV incidence testing.We used the BED capture immunoassay (BED) and an antibody avidity assay to test longitudinal samples from 51 HIV-infected Ugandan women infected with subtype A, C, D and intersubtype recombinant HIV who were enrolled in the HIVNET 012 trial (37 baseline samples collected near the time of delivery and 135 follow-up samples collected 3, 4 or 5 years later). Nineteen of 51 women were also pregnant at the time of one or more of the follow-up visits. The BED assay was performed according to the manufacturer's instructions. The avidity assay was performed using a Genetic Systems HIV-1/HIV-2 + O EIA using 0.1M diethylamine as the chaotropic agent.During the HIVNET 012 follow-up study, there was no difference in normalized optical density values (OD-n) obtained with the BED assay or in the avidity test results (%) when women were pregnant (n = 20 results) compared to those obtained when women were not pregnant (n = 115; for BED: p = 0.9, generalized estimating equations model; for avidity: p = 0.7, Wilcoxon rank sum). In addition, BED and avidity results were almost exactly the same in longitudinal samples from the 18 women who were pregnant at only one study visit during the follow-up study (p = 0.6, paired t-test).These results from 51 Ugandan women suggest that any changes in the antibody response to HIV infection that occur during pregnancy are not sufficient to alter results obtained with the BED and avidity assays. Confirmation with larger studies and with other HIV subtypes is needed.Item Prevalence and Predictors of Persistent Human Immunodeficiency Virus Viremia and Viral Rebound After Universal Test and Treat: A Population-Based Study(The Journal of infectious diseases, 2021) Grabowski, M. Kate; Patel, Eshan U.; Nakigozi, Gertrude; Ssempijja, Victor; Ssekubugu, Robert; Ssekasanvu, Joseph; Ndyanabo, Anthony; Kigozi, Godfrey; Nalugoda, Fred; Gray, Ronald H.; Kalibbala, Sarah; Serwadda, David M.; Laeyendecker, Oliver; Wawer, Maria J.; Chang, Larry W.; Quinn, Thomas C.; Kagaayi, Joseph; Tobian, Aaron A. R.; Reynolds, Steven J.UNAIDS targets for human immunodeficiency virus (HIV) epidemic control by 2030 include that 86% of all HIV-positive persons be on antiretroviral therapy (ART) and achieve HIV viral load (VL) suppression [1]. The major policy initiative underpinning this target is universal test and treat (UTT), whereby all HIV-positive persons, irrespective of CD4 count or severity of illness, are immediately prescribed ART [2]. In sub-Saharan Africa, which accounts for more than half of all new HIV diagnoses globally, there has been considerable progress in increasing ART coverage [Item Previously Transmitted HIV-1 Strains Are Preferentially Selected During Subsequent Sexual Transmissions(The Journal of infectious diseases, 2012) Redd, Andrew D.; Collinson-Streng, Aleisha N.; Chatziandreou, Nikolaos; Mullis, Caroline E.; Laeyendecker, Oliver; Martens, Craig; Ricklefs, Stacy; Kiwanuka, Noah; Hninn Nyein, Phyu; Grabowski, Mary K.; Kong, Xiangrong; Manucci, Jordyn; Sewankambo, Nelson; Wawer, Maria J.; Gray, Ronald H.; Porcella, Stephen F.; Fauci, Anthony S.; Sagar, Manish; Serwadda, David; Quinn, Thomas C.A genetic bottleneck is known to exist for human immunodeficiency virus (HIV) at the point of sexual transmission. However, the nature of this bottleneck and its effect on viral diversity over time is unclear. Methods. Interhost and intrahost HIV diversity was analyzed in a stable population in Rakai, Uganda, from 1994 to 2002. HIV-1 envelope sequences from both individuals in initially HIV-discordant relationships in which transmission occurred later were examined using Sanger sequencing of bulk polymerase chain reaction (PCR) products (for 22 couples), clonal analysis (for 3), and next-generation deep sequencing (for 9). Results. Intrahost viral diversity was significantly higher than changes in interhost diversity (P < .01). The majority of HIV-1–discordant couples examined via bulk PCR (16 of 22 couples), clonal analysis (3 of 3), and next-generation deep sequencing (6 of 9) demonstrated that the viral populations present in the newly infected recipient were more closely related to the donor partner’s HIV-1 variants found earlier during infection as compared to those circulating near the estimated time of transmission (P = .03). Conclusions. These findings suggest that sexual transmission constrains viral diversity at the population level, partially because of the preferential transmission of ancestral as opposed to contemporary strains circulating in the transmitting partner. Future successful vaccine strategies may need to target these transmitted ancestral strains.Item SARS-CoV-2 seroprevalence among blood donors in Uganda: 2019–2022(John Wiley & Sons, Ltd, 2023-05-16) Bloch, Evan M; Kyeyune, Dorothy; White, Jodie L; Ddungu, Henry; Ashokkumar, Swetha; Habtehyimer, Feben; Baker, Owen; Kasirye, Ronnie; Patel, Eshan U.; Grabowski, M. Kate; Musisi, Ezra; Moses, Khan; Hume, Heather A; Lubega, Irene; Shrestha, Ruchee; Motevalli, Mahnaz; Fernandez, Reinaldo E; Reynolds, Steven J; Redd, Andrew D; Wambongo Musana, Hellen; Dhabangi, Aggrey; Ouma, Joseph; Eroju, Priscilla; Lange, Telsa; Fowler, Mary Glenn; Musoke, Philippa; Stramer, Susan L.; Whitby, Denise; Zimmerman, Peter A; McCullough, Jeffrey; Sachithanandham, Jaiprasath; Pekosz, Andrew; Goodrich, Raymond; Quinn, Thomas C; Ness, Paul M.; Laeyendecker, Oliver; Tobian, Aaron A. R.Abstract Abstract Background The true burden of COVID‐19 in low‐ and middle‐income countries remains poorly characterized, especially in Africa. Even prior to the availability of SARS‐CoV‐2 vaccines, countries in Africa had lower numbers of reported COVID‐19 related hospitalizations and deaths than other regions globally. Methods Ugandan blood donors were evaluated between October 2019 and April 2022 for IgG antibodies to SARS‐CoV‐2 nucleocapsid (N), spike (S), and five variants of the S protein using multiplexed electrochemiluminescence immunoassays (MesoScale Diagnostics, Rockville, MD). Seropositivity for N and S was assigned using manufacturer‐provided cutoffs and trends in seroprevalence were estimated by quarter. Statistically significant associations between N and S antibody seropositivity and donor characteristics in November–December 2021 were assessed by chi‐square tests. Results A total of 5393 blood unit samples from donors were evaluated. N and S seropositivity increased throughout the pandemic to 82.6% in January–April 2022. Among seropositive individuals, N and S antibody levels increased ≥9‐fold over the study period. In November–December 2021, seropositivity to N and S antibody was higher among repeat donors (61.3%) compared with new donors (55.1%; p = .043) and among donors from Kampala (capital city of Uganda) compared with rural regions ( p = .007). Seropositivity to S antibody was significantly lower among HIV‐seropositive individuals (58.8% vs. 84.9%; p = .009). Conclusions Despite previously reported low numbers of COVID‐19 cases and related deaths in Uganda, high SARS‐CoV‐2 seroprevalence and increasing antibody levels among blood donors indicated that the country experienced high levels of infection over the course of the pandemic.