Systematic Identification of Correlates of HIV-1 Infection: An X-Wide Association Study in Zambia

Abstract Background HIV-1 remains the leading cause of death among adults in Sub-Saharan Africa, and over 1 million people are infected annually. Better identification of at-risk groups could benefit prevention and treatment programmes. We systematically identified factors related to HIV-1 infection in two nationally representative cohorts of women that participated in Zambia’s Demographic and Health Surveys (DHS). Methods We conducted a comprehensive analysis to identify and replicate the association of 1,415 social, economic, environmental, and behavioral indicators with HIV-1 status. We used the 2007 and 2013-2014 DHS surveys conducted among 5,715 and 15,433 Zambian women, respectively (727 indicators in 2007; 688 in 2013-2014; 688 in both). We used false discovery rate criteria to identify indicators that are strongly associated with HIV-1 in univariate and multivariate models in the entire population, as well as in subgroups stratified by wealth, residence, age, and history of HIV-1 testing. Findings In the univariate analysis we identified 102 and 182 variables that are associated with HIV-1 in the 2007 and 2013-2014 surveys, respectively, among which 79 were associated in both. Variables that were associated with HIV-1 status in all full-sample models (unadjusted and adjusted) as well as in at least 17 out of 18 subgroups include being formerly in a union (adjusted OR 2007 2.8, p<10 −16 ; 2013-2014 2.8, p<10 −29 ), widowhood (adjusted OR 2007 3.7, p<10 −12 ; 2013-2014 4.2, p<10 −30 ), history of genital ulcers in the last 12 months (adjusted 2007 OR 2.4, p<10 −5 ; 2013-2014 2.2, p<10 −6 ), and having a woman for the head of the household (2007 OR 1.7, p<10 −7 ; 2013-2014 OR 2.1, p<10 −26 ), while owning a bicycle (adjusted 2007 OR 0.6, p<10 −6 ; 2013-2014 0.6, p<10 −8 ) and currently breastfeeding (adjusted 2007 OR 0.5, p<10 −9 ; 2013-2014 0.4, p<10 −26 ) were associated with decreased risk. Using the identified variables, area under the curve for HIV-1 positivity ranged from 0.76 to 0.82. Interpretation Our X-wide association study in Zambian women identifies multiple under-recognized factors correlated with HIV-1 infection in 2007 and 2013-2014, including widowhood, breastfeeding, and being the head of the household. These variables could be used to improve HIV-1 testing and identification programs.