Browsing by Author "Grabowski, Mary K."
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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 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 HIV viral suppression and geospatial patterns of HIV antiretroviral therapy treatment facility use in Rakai, Uganda(AIDS (London, England), 2018) Billioux, Veena G.; Grabowski, Mary K.; Ssekasanvu, Joseph; Reynolds, Steven J.; Berman, Amanda; Bazaale, Jeremiah; Patel, Eshan U.; Bugos, Eva; Ndyanabo, Anthony; Kisakye, Alice; Kagaayi, Joseph; Gray, Ronald H.; Nakigozi, Gertrude; Ssekubugu, Robert; Nalugoda, Fred; Serwadda, David; Wawer, Maria J.; Chang, Larry W.To assess geospatial patterns of HIV antiretroviral therapy (ART) treatment facility use and whether they were impacted by viral load (VL) suppression. Methods—We extracted data on the location and type of care services utilized by HIV-positive persons accessing ART between February 2015 and September 2016 from the Rakai Community Cohort Study (RCCS) in Uganda. The distance from RCCS households to facilities offering ART was calculated using the open street map road network. Modified Poisson regression was used to identify predictors of distance traveled and, for those traveling beyond their nearest facility, the probability of accessing services from a tertiary care facility. Results—1554 HIV-positive participants were identified, of whom 68% had initiated ART. The median distance from households to the nearest ART facility was 3.10 km (Interquartile range, IQR, 1.65–5.05), but the median distance traveled was 5.26 km (IQR, 3.00–10.03, p<0.001) and 57% of individuals travelled further than their nearest facility for ART. Those with higher education and wealth were more likely to travel further. 93% of persons on ART were virally suppressed, and there was no difference in the distance traveled to an ART facility between those with suppressed and unsuppressed VLs (5.26 km vs. 5.27 km, p=0.650). Conclusions—Distance traveled to HIV clinics was increased with higher socioeconomic status, suggesting that wealthier individuals exercise greater choice. However, distance traveled did not vary by those who were or were not virally suppressed.Item Human immunodeficiency virus care cascade among sub-populations in Rakai, Uganda: an observational study(Journal of the International AIDS Society, 2017) Billioux, Veena G.; Chang, Larry W.; Reynolds, Steven J.; Nakigozi, Gertrude; Ssekasanvu, Joseph; Grabowski, Mary K.; Ssekubugu, Robert; Nalugoda, Fred; Kigozi, Godfrey; Kagaayi, Joseph; Serwadda, David; Gray, Ronald H.; Wawer, Maria J.To assess progress towards the UNAIDS 90–90–90 initiative targets, we examined the HIV care cascade in the population-based Rakai Community Cohort Study (RCCS) in rural Uganda and examined differences between sub-groups. Methods: Self-reports and clinical records were used to assess the proportion achieving each stage in the cascade. Statistical inference based on a 2 test for categorical variables and modified Poisson regression were used to estimate prevalence risk ratios (PRRs) and 95% confidence intervals (CI) for enrolment into care and initiating antiretroviral therapy (ART). Results: From September 2013 through December 2015, 3,666 HIV-positive participants were identified in the RCCS. As of December 2015, 98% had received HIV Counseling and Testing (HCT), 74% were enrolled in HIV care, and 63% had initiated ART of whom 92% were virally suppressed after 12 months on ART. Engagement in care was lower among men than women (enrolment in care: adjPRR 0.84, 95% CI 0.77–0.91; ART initiation: adjPRR 0.75, 95% CI 0.69–0.82), persons aged 15–24 compared to those aged 30–39 (enrolment: adjPRR 0.72, 95% CI 0.63–0.82; ART: adjPRR 0.69, 95%CI 0.60–0.80), unmarried persons (enrolment: adjPRR 0.84, 95% CI 0.71–0.99; ART adjPRR 0.80, 95% CI 0.66–0.95), and new in-migrants (enrolment: adjPRR 0.75, 95% CI 0.67–0.83; ART: adjPRR 0.76, 95% CI 0.67–0.85). This cohort achieved 98–65–92 towards the UNAIDS “90–90–90” targets with an estimated 58% of the entire HIV-positive RCCS population virally suppressed. Conclusions: This cohort achieved over 90% in both HCT and viral suppression among ART users, but only 65% in initiating ART, likely due to both an ART eligibility criterion of <500 CD4 cells/mL and suboptimal entry into care among men, younger individuals, and in-migrants. Interventions are needed to promote enrolment in HIV care, particular for hard-to-reach subpopulations.Item Liver Stiffness Is Associated With Monocyte Activation in HIV-Infected Ugandans Without Viral Hepatitis(AIDS research and human retroviruses, 2013) Redd, Andrew D.; Wendel, Sarah K.; Grabowski, Mary K.; Ocama, Ponsiano; Kiggundu, Valerian; Bbosa, Francis; Boaz, Iga; Balagopal, Ashwin; Reynolds, Steven J.; Gray, Ronald H.; Serwadda, David; Kirk, Gregory D.; Quinn, Thomas C.; Stabinski, LaraA high prevalence of liver stiffness, as determined by elevated transient elastography liver stiffness measurement, was previously found in a cohort of HIV-infected Ugandans in the absence of chronic viral hepatitis. Given the role of immune activation and microbial translocation in models of liver disease, a shared immune mechanism was hypothesized in the same cohort without other overt causes of liver disease. This study examined whether HIV-related liver stiffness was associated with markers of immune activation or microbial translocation (MT). A retrospective case-control study of subjects with evidence of liver stiffness as defined by a transient elastography stiffness measurement ‡ 9.3 kPa (cases = 133) and normal controls (n = 133) from Rakai, Uganda was performed. Cases were matched to controls by age, gender, HIV, hepatitis B virus (HBV), and highly active antiretroviral therapy (HAART) status. Lipopolysaccharide (LPS), endotoxin IgM antibody, soluble CD14 (sCD14), C-reactive protein (CRP), and D-dimer levels were measured. Conditional logistic regression was used to estimate adjusted matched odds ratios (adjMOR) and 95% confidence intervals. Higher sCD14 levels were associated with a 19% increased odds of liver stiffness (adjMOR = 1.19, p = 0.002). In HIV-infected individuals, higher sCD14 levels were associated with a 54% increased odds of having liver stiffness (adjMOR = 1.54, p < 0.001); however, the opposite was observed in HIV-negative individuals (adjMOR = 0.57, p = 0.001). No other biomarker was significantly associated with liver stiffness, and only one subject was found to have detectable LPS. Liver stiffness in HIV-infected Ugandans is associated with increased sCD14 indicative of monocyte activation in the absence of viral hepatitis or microbial translocation, and suggests that HIV may be directly involved in liver disease.Item Migration and risk of HIV acquisition in Rakai, Uganda: a population-based cohort study(The lancet HIV, 2018) Olawore, Oluwasolape; Tobian, Aaron A. R.; Kagaayi, Joseph; Bazaale, Jeremiah M.; Nantume, Betty; Kigozi, Grace; Nankinga, Justine; Nalugoda, Fred; Nakigozi, Gertrude; Kigozi, Godfrey; Gray, Ronald H.; Wawer, Maria J.; Ssekubugu, Robert; Santelli, John S.; Reynolds, Steven J.; Chang, Larry W.; Serwadda, David; Grabowski, Mary K.In sub-Saharan Africa, migrants typically have higher HIV prevalence than non-migrants; however, whether HIV acquisition typically precedes or follows migration is unknown. We aimed to investigate the risk of HIV after migration in Rakai District, Uganda. Methods In a prospective population-based cohort of HIV-negative participants aged 15–49 years in Rakai, Uganda, between April 6, 1999, and Jan 30, 2015, we assessed the association between migration and HIV acquisition. Individuals were classified as recent in-migrants (≤2 years in community), non-recent in-migrants (>2 years in community), or permanent residents with no migration history. The primary outcome was incident HIV infection. We used Poisson regression to estimate incidence rate ratios (IRRs) of HIV associated with residence status with adjustment for demographics, sexual behaviours, and time. Data were also stratified and analysed within three periods (1999–2004, 2005–11, and 2011–15) in relation to the introduction of combination HIV prevention (CHP; pre-CHP, early CHP, and late CHP). Findings Among 26 995 HIV-negative people who participated in the Rakai Community Cohort Study survey, 15 187 (56%) contributed one or more follow-up visits (89 292 person-years of follow-up) and were included in our final analysis. 4451 (29%) were ever in-migrants and 10 736 (71%) were permanent residents. 841 incident HIV events occurred, including 243 (29%) among in-migrants. HIV incidence per 100 person-years was significantly increased among recent in-migrants compared with permanent residents, for both women (1·92, 95% CI 1·52–2·43 vs 0·93, 0·84–1·04; IRR adjusted for demographics 1·75, 95% CI 1·33–2·33) and men (1·52, 0·99–2·33 vs 0·84, 0·74–0·94; 1·74, 1·12–2·71), but not among non-recent in-migrants (IRR adjusted for demographics 0·94, 95% CI 0·74–1·19 for women and 1·28, 0·94–1·74 for men). Between the pre-CHP and late-CHP periods, HIV incidence declined among permanent resident men (p<0·0001) and women (p=0·002) and non-recent in-migrant men (p=0·031), but was unchanged among non-recent in-migrant women (p=0·13) and recent in-migrants (men p=0·76; women p=0·84) Interpretation The first 2 years after migration are associated with increased risk of HIV acquisition. Prevention programmes focused on migrants are needed to reduce HIV incidence in sub-Saharan Africa. Funding National Institute of Mental Health, the National Institute of Allergy and Infectious Diseases, the National Institute of Child Health and Development, the National Institute for Allergy and Infectious Diseases Division of Intramural Research, National Institutes of Health; the Centers for Disease Control and Prevention; the Bill & Melinda Gates Foundation; and the Johns Hopkins University Center for AIDS Research.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 Vaginal Cytomegalovirus Shedding Before and After Initiation of Antiretroviral Therapy in Rakai, Uganda(The Journal of infectious diseases, 2015) Gianella, Sara; Redd, Andrew D.; Grabowski, Mary K.; Tobian, Aaron A. R.; Serwadda, David; Newell, Kevin; Patel, Eshan U.; Kalibbala, Sarah; Ssebbowa, Paschal; Gray, Ronald H.; Quinn, Thomas C.; Reynolds, Steven J.Vaginal shedding of cytomegalovirus (CMV) DNA was determined longitudinally among 96 women coinfected with human immunodeficiency virus (HIV), herpes simplex virus 2, and CMV starting antiretroviral therapy (ART) during a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Vaginal CMV was detected in 75 of 96 women (78.0%) and 379 of 1080 individual visits (35.1%). ART status, higher HIV RNAviral load before ART initiation, and younger age were significantly associated with increased frequency of CMV shedding (P < .01). Compared to pre- ART, CMV shedding peaked from month 2 to month 4 after ART initiation, suggesting possible immune reconstitution inflammatory syndrome. Further studies need to determine the clinical significance of asymptomatic CMV shedding.