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HIV Prevention Efforts and Incidence of HIV in Uganda.

ABSTRACT: BACKGROUND:To assess the effect of a combination strategy for prevention of human immunodeficiency virus (HIV) on the incidence of HIV infection, we analyzed the association between the incidence of HIV and the scale-up of antiretroviral therapy (ART) and medical male circumcision in Rakai, Uganda. Changes in population-level viral-load suppression and sexual behaviors were also examined. METHODS:Between 1999 and 2016, data were collected from 30 communities with the use of 12 surveys in the Rakai Community Cohort Study, an open, population-based cohort of persons 15 to 49 years of age. We assessed trends in the incidence of HIV on the basis of observed seroconversion data, participant-reported use of ART, participant-reported male circumcision, viral-load suppression, and sexual behaviors. RESULTS:In total, 33,937 study participants contributed 103,011 person-visits. A total of 17,870 persons who were initially HIV-negative were followed for 94,427 person-years; among these persons, 931 seroconversions were observed. ART was introduced in 2004, and by 2016, ART coverage was 69% (72% among women vs. 61% among men, P<0.001). HIV viral-load suppression among all HIV-positive persons increased from 42% in 2009 to 75% by 2016 (P<0.001). Male circumcision coverage increased from 15% in 1999 to 59% by 2016 (P<0.001). The percentage of adolescents 15 to 19 years of age who reported never having initiated sex (i.e., delayed sexual debut) increased from 30% in 1999 to 55% in 2016 (P<0.001). By 2016, the mean incidence of HIV infection had declined by 42% relative to the period before 2006 (i.e., before the scale-up of the combination strategy for HIV prevention) - from 1.17 cases per 100 person-years to 0.66 cases per 100 person-years (adjusted incidence rate ratio, 0.58; 95% confidence interval [CI], 0.45 to 0.76); declines were greater among men (adjusted incidence rate ratio, 0.46; 95% CI, 0.29 to 0.73) than among women (adjusted incidence rate ratio, 0.68; 95% CI, 0.50 to 0.94). CONCLUSIONS:In this longitudinal study, the incidence of HIV infection declined significantly with the scale-up of a combination strategy for HIV prevention, which provides empirical evidence that interventions for HIV prevention can have a population-level effect. However, additional efforts are needed to overcome disparities according to sex and to achieve greater reductions in the incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

SUBMITTER: Grabowski MK

PROVIDER: S-EPMC5627523 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:HIV incidence has been declining in Africa with scale-up of HIV interventions. However, there is limited data on HIV evolutionary trends in African populations with waning epidemics. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a twenty-five-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort. Gag (p24) and env (gp41) HIV data were generated from persons living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994 to 2018) and four hyperendemic Lake Victoria fishing communities (2011 to 2018) under continuous surveillance. HIV subtype was assigned using the Recombination Identification Program with phylogenetic confirmation. Inter-subtype diversity was estimated using the Shannon diversity index and intra-subtype diversity with the nucleotide diversity and pairwise TN93 genetic distance. Genetic divergence was measured using root-to-tip distance and pairwise TN93 genetic distance analyses. Evolutionary dynamics were assessed among demographic and behavioral sub-groups, including by migration status. 9,931 HIV sequences were available from 4,999 PLHIV, including 3,060 and 1,939 persons residing in inland and fishing communities, respectively. In inland communities, subtype A1 viruses proportionately increased from 14.3% in 1995 to 25.9% in 2017 (p<0.001), while those of subtype D declined from 73.2% in 1995 to 28.2% in 2017 (p<0.001). The proportion of viruses classified as recombinants significantly increased by more than four-fold. Inter-subtype HIV diversity has generally increased. While p24 intra-subtype genetic diversity and divergence leveled off after 2014, diversity and divergence of gp41 increased through 2017. Inter- and intra-subtype viral diversity increased across all population sub-groups, including among individuals with no recent migration history or extra-community sexual partners. This study provides insights into population-level HIV evolutionary dynamics in declining African HIV epidemics following the scale-up of HIV prevention and treatment programs. Continued molecular surveillance may provide a better understanding of the dynamics driving population HIV evolution and yield important insights for epidemic control and vaccine development.

Project description:Background:Civil war in Northern Uganda resulted in widespread atrocities, human rights violations, and death, and caused millions to flee to internally displaced persons camps. War-related traumas combined with difficulties accessing HIV prevention and health services has led to extreme HIV-related vulnerability among conflict-affected people who survived the war. Objectives were to (1) determine HIV incidence among conflict-affected people in Northern Uganda and (2) identify vulnerabilities associated with HIV infection. Methods:The Cango Lyec (Healing the Elephant) Project is a prospective cohort involving conflict-affected populations in three districts in Northern Uganda. In 2011, eight randomly selected communities were mapped, and a census was conducted. Consenting participants aged 13-49 years were followed over three rounds of follow-up. Longitudinal data collected included war-related experiences, sexual vulnerabilities, and sociodemographics. Blood samples were tested for HIV-1 at baseline and each 12-month follow-up. Multivariable Cox proportional hazard models determined factors associated with HIV incidence. Findings:Overall, 1920 baseline HIV-negative participants with at least one follow-up contributed 3877 person-years (py) for analysis. Thirty-nine (23 female, 16 male) participants contracted HIV during follow-up. Age- and gender-standardised HIV incidence rate was 10•2 per 1000py (95%CI: 7•2-14•0). Stratified by sex, the age-adjusted HIV incidence was 11•0 per 1000py (95%CI: 6•9-16•6) among women and 9•4 per 1000py (95%CI: 5•3-15•3) among men. Adjusting for confounders, factors associated with risk of HIV included: having been abducted (HR: 3•70; 95%CI: 1•87-7•34), experiencing ?12 war-related traumatic events (HR: 2•91 95%CI: 1•28-6•60), suicide ideation (HR: 2•83; 95%CI: 1•00-8•03), having ?2 sexual partners (HR: 4•68; 95%CI: 1•36-16•05), inconsistent condom use (HR: 6•75; 95%CI: 2•49-18•29), and self-reported genital ulcers (HR: 4•39; 95%CI: 2•04-9•45). Interpretation:Conflict-affected participants who had experienced abduction and multiple traumas during the war were at greater risk of HIV infection. Trauma-informed HIV prevention and treatment services, and culturally-safe mental health initiatives, are urgent for Northern Uganda.

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HIV Prevention Efforts and Incidence of HIV in Uganda.

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