A model of tuberculosis screening for pregnant women in resource-limited settings using Xpert MTB/RIF.

Timely diagnosis and treatment of maternal tuberculosis (TB) is important to reduce morbidity and mortality for both the mother and child, particularly in women who are coinfected with HIV. The World Health Organization (WHO) recommends the integration of TB/HIV screening into antenatal services but available diagnostic tools are slow and insensitive, resulting in delays in treatment initiation. Recently the WHO endorsed Xpert MTB/RIF, a highly sensitive, real-time PCR assay for Mycobacterium tuberculosis that simultaneously detects rifampicin resistance directly from sputum and provides results within 100 minutes. We propose a model for same-day TB screening and diagnosis of all pregnant women at antenatal care using Xpert MTB/RIF. Pilot studies are urgently required to evaluate strategies for the integration of TB screening into antenatal clinics using new diagnostic technologies.

Improved HIV testing coverage after scale-up of antiretroviral therapy programs in urban Zambia: Evidence from serial hospital surveillance.

BACKGROUND: We evaluated changing HIV testing coverage and prevalence rates before and after expanding city-wide antiretroviral therapy (ART) programs in Lusaka, Zambia. METHODS: We conducted serial cross-sectional surveys on the University Teaching Hospital medical ward to assess HIV prevalence among inpatients of unknown status in 2003 and 2006. Willing participants received counseling and dual HIV rapid tests. We compared the proportion of inpatients receiving their test results in 2003 (off-the-ward testing) to 2006 (on-the-ward). RESULTS: In 2003, none of 103 inpatients knew their HIV status or took ART; 99.0% (102/103) agreed to testing. In 2006, 49.3% (99 of 201) patients knew they were HIV-infected and were on ART; of those with unknown status, 98.0% (100/102) agreed to testing. In 2003, only 54.9% (56/102) received post-test counseling and 98.2% (55/56) learned their status. In 2006, 99.0% (99/100) received post-test counseling and 99.1% (98 of 99) learned their status. In 2003, 62.8% (64 of 102) of status-unknown inpatients who agreed to testing were seropositive by dual rapid test, compared to 48.0% (48 of 100) of status-unknown inpatients in 2006. When including inpatients who already knew their seropositive status plus those unknowns who tested seropositive, the proportion of inpatients that was seropositive in 2006 was 73.1% (147 of 201), higher than in 2003. CONCLUSIONS: After ART program expansion, inpatients in 2006 were far more likely than their 2003 counterparts to know their HIV status and to be taking ART. In both years, 63-73% of medical inpatients were HIV-infected and 98.5% of inpatients agreed to testing. On-the-ward testing in 2006 avoided the 2003 problem of patient discharge before learning of their test results. Hospital-based HIV testing is an essential clinical service in high prevalence settings and can serve further as a surveillance system to help track the community impact of outpatient AIDS services in Africa.

Modified Kigali combined staging predicts risk of mortality in HIV-infected adults in Lusaka, Zambia.

We assessed the utility of the modified Kigali combined (MKC) staging system for predicting survival in HIV-infected Zambian adults in a prospective, longitudinal, open cohort. From 1995 to 2004, HIV-discordant couples (one HIV-infected partner and one HIV-negative partner) were recruited from couples' voluntary counseling and testing centers in Lusaka, Zambia and followed at 3-month intervals. MKC stage, which incorporates clinical stage with erythrocyte sedimentation rate (ESR), hematocrit, and body mass index (BMI), was determined at enrollment. Kaplan-Meier survival and Cox proportional hazard methods were used to calculate median survival and relative hazards. We enrolled 1479 HIV-discordant couples with a combined 7305 person-years of follow-up. Among HIV-infected participants over the 9-year study period, there were 333 confirmed deaths. The time to 50% mortality was 8.5 years with MKC stage 1 and 2 disease compared to 3.7 years with MKC stage 4 disease at enrollment. Survival rates at 3 years were 85% with MKC stage 1 and 2 disease, 74% with MKC stage 3 disease, and 51% with MKC stage 4 disease. A total of 275 HIV-negative partners seroconverted during follow-up. In comparison, survival rates at 3 years were 94% for HIV-negative participants and 92% for participants who seroconverted during follow-up. In multivariate analysis, MKC stage 4 disease (HR = 3.7, 95% CI = 2.7-5.0) remained a strong predictor of mortality. Incorporating ESR, hematocrit, and BMI with clinical staging is a powerful, low-cost tool to identify HIV-infected adults at high risk for mortality.

Transmission of HIV-1 and HLA-B allele-sharing within serodiscordant heterosexual Zambian couples.

Factors that might increase risk of HIV-1 transmission include age, sex, and amount of HIV-1 RNA in plasma, but findings for HLA allele-sharing are not in agreement. We tested the hypothesis that allele sharing at HLA loci is associated with increased risk of transmission of HIV-1 infection in cohabiting heterosexual Zambian couples. We studied 125 initially serodiscordant partners with sequence-confirmed interpartner HIV-1 transmission and 104 couples who were persistently serodiscordant, and we analysed relations with molecularly typed HLA-A, B, and C alleles by survival techniques. After adjustment for other genetic and non-genetic risk factors seen with heterosexual transmission of HIV-1 in this cohort, sharing of HLA-B alleles was independently associated with accelerated intracouple transmission (relative hazard 2.23, 95% CI 1.52-3.26, p<0.0001). Selective pressure by HLA-B alleles on transmitted viruses accords with current understanding of the effect of B locus polymorphism in HIV-1 and perhaps other infections.