A total of 2375 participants were examined, 482 in South Africa, 539 in Zimbabwe, and 1354 in Uganda. Overall, 42 (1.8%) of individuals were classified as equivocal in HHV-8 antibody testing and not considered in the primary analysis, leaving 471 participants in South Africa, 532 in Zimbabwe, and 1330 in Uganda. Of those in the primary analysis, the median age was 28 years (interquartile range [IQR] 21 to 37) in South Africa, 29 years (IQR 25 to 33) in Zimbabwe, and 22 years (IQR 19 to 28) in Uganda. In Uganda, 21.4% of participants were women, and by design, all participants in South Africa and Zimbabwe were women. Prevalence of HIV infection among South African participants was 38.2%, while, by design, 63.7% of Zimbabwe participants and no Uganda participants were HIV-infected.
Crude HHV-8 seroprevalence was 37.3% in Uganda, 20.3% in Zimbabwe, and 17.6% in South Africa. This equates to, unadjusted for age, Ugandans having 2.33-fold greater odds (95% confidence interval [CI] 1.83 to 2.95, p < 0.001) of being HHV-8-infected than Zimbabweans and a 2.77-fold greater odds (95% CI 2.13 to 3.60, p < 0.001) than South Africans. The high seroprevalence of HHV-8 infection in Uganda was apparent early in adulthood, with 35.5% of participants infected before age 21 years (). The higher seroprevalence in Uganda did not substantially change throughout adulthood, only rising to 43.4% in those 41 years or older (p = 0.30 for age trend). In contrast, HHV-8 seroprevalence was substantially lower amongst the youngest participants in Zimbabwe and South Africa (13.7% and 10.8%, respectively, in those 25 years and younger), but then increased significantly with age in both Zimbabwe (p = 0.023) and South Africa (p < 0.001). Gender differences were evaluable only in Uganda, where infection was more common among men (38.6%) than among women (32.0%, p = 0.085). In both South Africa and Zimbabwe, HHV-8 infection appeared to be unrelated to HIV infection status (p = 0.44 and p = 0.40, respectively).
Factors associated with HHV-8 infection in South Africa, Zimbabwe, and Uganda.
To formally compare HHV-8 seroprevalence across countries, we restricted the analysis to only the 1287 women—all of the participants from South Africa and Zimbabwe and the 284 women from Uganda—given the slightly higher seroprevalence among men in Uganda. In a multivariable logistic regression analysis adjusting for age, there was no strong evidence for a difference in HHV-8 seroprevalence in Zimbabwe versus South Africa (odds ratio [OR] = 1.32, 95% CI 0.95 to 1.83; p = 0.095). In contrast, Ugandans had a 3.24-fold greater odds (95% CI 2.19 to 4.81; p < 0.001) of being HHV-8-infected than South Africans and a 2.22-fold greater odds (95% CI 1.49 to 3.30; p < 0.001) than Zimbabweans. Because there was no significant difference between South Africa and Zimbabwe, we combined participants from these two countries and found that Ugandans had a 2.72-fold greater odds (95% CI 1.96 to 3.79; p < 0.001) of being HHV-8-infected than the combination of South Africans and Zimbabweans (). When we further restricted the analysis to just those participants who were HIV-uninfected, the inferences were unchanged. Among HIV-uninfected individuals, Ugandans had a 3.47-fold greater odds (95% CI 2.14 to 5.62; p < 0.001) of being HHV-8-infected than South Africans and a 2.06-fold greater odds (95% CI 1.27 to 3.33; p = 0.004) than Zimbabweans. Finally, we used the multivariable model to determine whether the relationship between age and HHV-8 infection differed by country, as suggested by the within-in country analyses above. We found no evidence that the effect of age on HHV-8 seroprevalence differed in Zimbabwe vs. South Africa (p = 0.89 for interaction term). While we did find suggestive evidence that the effect of age differed in Uganda versus the combined population of South Africa and Zimbabwe, we cannot exclude that this is chance occurrence (p = 0.13 for interaction term).
Comparison of HHV-8 seroprevalence in women in South Africa, Zimbabwe, and Uganda using different antibody interpretation algorithms.
To determine if our finding of a significant difference in HHV-8 seroprevalence in Uganda versus either Zimbabwe or South Africa was dependent on the base-case algorithm we used to determine seropositivity, we also evaluated a number of other algorithms by which to interpret our antibody assays. We found that the principal inferences—no difference between South Africa and Zimbabwe but substantially higher seroprevalence in Uganda than in either Zimbabwe or South Africa—were unchanged regardless of the algorithm used (). In the most strict algorithm, where reactivity in all three antibody assays is required to determine overall seropositivity, the unadjusted country-specific estimates of HHV-8 seroprevalence were predictably the lowest (South Africa: 6.8%; Zimbabwe: 5.6%; Uganda: 8.2%), but nonetheless after age-adjustment, Ugandans again had a 2.64-fold greater odds of being HHV-8-infected than the South African and Zimbabweans. The least strict algorithm, where reactivity in any one of the three assays was deemed seropositive, produced the highest country-specific prevalence estimates (South Africa: 23.1%; Zimbabwe: 24.7%; Uganda: 47.1%), with Ugandans again having significantly greater seroprevalence. We also evaluated algorithms where we considered all the equivocal results as either reactive or non-reactive, and again the principal findings were unchanged.