Systematic identification of correlates of HIV infection: an X-wide association study.

Objective: Better identification of at-risk groups could benefit HIV-1 care programmes. We systematically identified HIV-1 risk factors in two nationally representative cohorts of women in the Demographic and Health Surveys.
Methods: We identified and replicated the association of 1415 social, economic, environmental, and behavioral factors with HIV-1 status. We used the 2007 and 2013-2014 surveys conducted among 5715 and 15 433 Zambian women, respectively (688 shared factors). We used false discovery rate criteria to identify factors that are strongly associated with HIV-1 in univariate and multivariate models of the entire population, as well as in subgroups stratified by wealth, residence, age, and past HIV-1 testing.
Results: In the univariate analysis, we identified 102 and 182 variables that are associated with HIV-1 in the two surveys, respectively (79 factors were associated in both). Factors that were associated with HIV-1 status in full-sample analyses and in subgroups include being formerly married (adjusted OR 2007, 2.8, P < 10(-16); 2013-2014 2.8, P < 10(-29)), widowhood (aOR 3.7, P < 10(-12); and 4.2, P < 10(-30)), genital ulcers within 12 months (aOR 2.4, P < 10(-5); and 2.2, P < 10(-6)), and having a woman head of the household (aOR 1.7, P < 10(-7); and 2.1, P < 10(-26), while owning a bicycle (aOR 0.6, P < 10(-6); and 0.6, P < 10(-8)) and currently breastfeeding (aOR 0.5, P < 10(-9); and 0.4, P < 10(-26)) were associated with decreased risk. Area under the curve for HIV-1 positivity was 0.76-0.82.
Conclusion: Our X-wide association study identifies under-recognized factors related to HIV-1 infection, including widowhood, breastfeeding, and gender of head of the household. These features could be used to improve HIV-1 identification programs.