Associations of T-cell phenotypes with persistent oral thrush at CD4 positive cell counts greater than 500 per cubic millimeter and their interactions with progression of HIV disease (Immune deficiency).

摘要

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.