Immunopathogenesis and diagnosis of tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome during early antiretroviral therapy.

BACKGROUND: In many settings, the benefits of antiretroviral therapy (ART) are reduced by the high early incidence of tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). METHODS: We used tuberculin skin testing and the QuantiFERON-TB Gold In-Tube assay to investigate cellular immune responses to purified protein derivative (PPD) and region of difference 1 (RD1) antigens during the first 24 weeks of ART. RESULTS: TB-IRIS and ART-associated tuberculosis occurred in 15 of 75 (20%) and 11 of 231 (4.8%) participants at risk, respectively. Greater increases in interferon gamma (IFN-gamma) and skin test responses to PPD were seen at week 24 and 12 in participants with TB-IRIS (P< or = .04), respectively. Raw IFN-gamma responses to RD1 antigens and PPD corrected for pre-ART CD4(+) T cell counts were higher at all time points in individuals with ART-associated tuberculosis (P<.001) and were associated with areas under receiver operator characteristic curves of 0.90 for RD1 (95% confidence interval [CI], 0.78-1.00) and 0.92 for PPD (95% CI, 0.83-1.00) for the diagnosis of ART-associated tuberculosis. Pre-ART IFN-gamma responses enabled stratification of participants into groups with risks of subsequent tuberculosis of 0.7%, 9.3%, and 30.0%. CONCLUSIONS: Type 1 effector T cell responses are prominent in ART-associated tuberculosis, but additional immune defects may be more important in paradoxical TB-IRIS. IFN-gamma release assays may contribute to the prediction and diagnosis of tuberculosis during early ART.

Implementation and Operational Research: Integration of Family Planning Services in a Peer-Managed HIV Care Clinic Serving Most-at-Risk Populations in Phnom Penh, Cambodia.

OBJECTIVE: To assess contraceptive uptake and method choice among women living with HIV (WLHIV) attending an HIV care clinic serving most-at-risk women in Phnom Penh, Cambodia, before and after the implementation of family planning (FP) services. METHODS: Semistructured questionnaires were administered to clients before (July, 2011) and after (July, 2012) FP service implementation with provision of contraceptive methods (pills, injectables, implants, and intrauterine device [IUD]). RESULTS: Among 250 and 249 clients interviewed before and after implementation respectively, 24.5% of women reported selling sex for money during the last 6 months before and 35.3% after implementation. Awareness about contraceptive methods significantly increased among clients postimplementation. Among sexually active women, male condom remained the contraceptive method of choice with an overall condom use during the last 6 months at 91% postimplementation vs. 95.6% preimplementation (P = 0.11). Although the use of noncondom FP methods increased but not significantly (16.4% after vs. 12.6% before implementation, P = 0.8), the use of dual method (condom plus another method) remained low and did not significantly increase after implementation (14.8% after vs. 11.0% before, P = 0.28). CONCLUSIONS: Our results show that FP practices of WLHIV attending an HIV care clinic for most-at-risk populations did not significantly change after integration on-site provision of a wide range of FP methods. Innovative strategies and further research are needed to better understand how to promote the use of noncondom FP methods and prevent unwanted pregnancies and abortions among most-at-risk women and WLHIV.