Prevalence and determinants of Kaposi's sarcoma-associated herpesvirus (KSHV) antibody positivity among adults living with HIV in East Africa

Background: Persons living with HIV (PLHIV) who are also infected with Kaposi sarcoma-associated herpesvirus (KSHV) constitute a group among the highest risk for Kaposi sarcoma (KS). As such, understanding KSHV prevalence amongst PLHIV is important for the control of KS. To date, data on KSHV prevalence amongst PLHIV in East Africa - one of the world's hotbeds for KS - is both sparse and variable. Methods: In a cross-sectional design, we studied consecutive adult PLHIV identified just prior to starting antiretroviral therapy at an ambulatory HIV clinic in Mbarara, Uganda. Results from two enzyme immunoassays (with synthetic K8.1 and ORF 65 antigens as targets) and one immunofluorescence assay (using induced BCBL cells) to detect antibodies to KSHV were combined to classify KSHV antibody positivity. Results: We evaluated 727 PLHIV between 2005 to 2013; median age was 34 years (interquartile range (IQR): 28-40), 69% were women, and median CD4 count was 167 cells/l (IQR: 95-260). Prevalence of KSHV antibody positivity was 42% (95% CI: 38%-46%), with little substantive change after several correction approaches, including Rogan-Gladen. Adjusted prevalence of KSHV antibody positivity was 1.6 times (95% CI: 1.3-1.9) higher in men than women; adjusted absolute prevalence difference was +0.20 (95% CI: +0.11 to +0.30). Lack of formal education (prevalence ratio=1.6 comparing no school to [≥]4 years of secondary school; 95% CI: 1.1-2.3) was also associated with KSHV infection. We found no strong evidence for a role for age, alcohol use, or other measurements of sexual behavior, SES, or well-being in the occurrence of KSHV antibody positivity. Conclusion: Among adult PLHIV in western Uganda, KSHV prevalence is estimated at 42%, with little change after several approaches to correction for antibody detection inaccuracy. This estimate differs from several others in the region (up to 83%), highlighting need for inter-assay comparison studies using identical local specimens. To the extent HIV does not influence KSHV acquisition, the findings may also represent KSHV prevalence in the general population. The large-magnitude effect of sex and education on KSHV acquisition motivates an accelerated search for mechanisms. The sex effect, in part, may explain the higher incidence of KS among men.