| Objectives. The study had two aims: (1) to determine whether specific T-cell phenotypes associated with function, activation and maturity were associated with persistent oral thrush in HIV-infected men with high (>500/mm3) CD4+ cell counts, and (2) to determine how much of the documented association between oral thrush and HIV disease progression could be explained by these T-cell phenotypes.; Setting. Nested case-control study (Aim 1) and nested prospective study (Aim 2) within an ongoing cohort of HIV-1 positive gay men in Baltimore, MD, Pittsburgh, PA, Chicago, IL, and Los Angeles, CA.; Methods. We evaluated percent expression of T-cell phenotypes in HIV-1+ men categorized by oral thrush status (with/without) and high (>500/mm 3) CD4+ cell count. Markers evaluated include CD28 (T-cell function), CD38 (T-cell activation), HLA-DR (T-cell activation), and CD45RO/RA (T-cell maturity). Risk of oral thrush was analyzed using matched pairs analysis and multivariate regression models. We compared time to PCP, AIDS and death by oral thrush status, T-cell phenotype and HIV RNA using survival analysis and multivariate models (Cox proportional hazards) to determine the extent phenotypes and viral load explained different rates of progression.; Results. In univariate analyses (case-control), increased CD4+DR+38+ (OR = 1.09, p = 0.033) and decreased CD4+DR−38− (OR = 0.963, p = 0.042) were associated with oral thrush; and HIV RNA was marginally associated with oral thrush (OR = 1.65, p = 0.059). Smoking one year prior was associated with oral thrush (OR = 1.60, 95% CI = 0.69–3.78). In multivariate analyses both phenotypes remain associated with oral thrush (OR = 1.09, p = 0.060 for CD4+DR+38+ and OR = 0.93, p = 0.020 for CD4+DR−38−) after adjustment for HIV-1 RNA, prior CD4+ cell count and smoking one year prior.; Prospective analysis of association between exposures (T-cell phenotypes, HIV RNA and oral thrush) and outcomes (time to PCP, AIDS and death) found cases progressed to AIDS and death faster than controls (RH = 1.74, p = 0.070 for AIDS; and RH = 1.87, p = 0.083 for death). Higher HIV RNA was strongly associated with progression to first PCP (RH = 3.19, p = 0.006), AIDS (RH = 3.24, p < 0.001) and death (RH = 3.14, p < 0.001). Higher CD4+DR+38+ and lower CD4+DR−38− levels were consistently associated with disease progression (RH range = 1.42–3.84). After adjustment by HIV RNA alone and in combination with each phenotype, the association between oral thrush and progression (PCP, AIDS and death) weakened substantially. Adjustment for CD4+DR+38+ alone had no effect on the association. However, adjustment by CD4+DR−38− decreased the association between oral thrush and AIDS or death, but adjustment had little effect on progression to PCP.; Conclusions. Two phenotypes were associated with oral thrush, but only one, CD4+DR−38−, contributed to the explanation of the association between oral thrush and HIV-1 disease progression. HIV-1 viral burden explained a significant part, but not all of the association between oral thrush and disease progression. |
