High rates of viral suppression in a cohort of HIV-positive adults receiving ART in Ethiopian health centers irrespective of concomitant tuberculosis.

INTRODUCTION: Antiretroviral therapy (ART) initiation during treatment for tuberculosis (TB) improves survival in HIV/TB co-infected patients. Data on ART outcome for HIV/TB co-infected patients managed in primary health care in low-income regions is limited. We compared virological suppression rates, mortality and retention in care in HIV-positive adults receiving care in five Ethiopian health centres with regard to TB co-infection. MATERIALS AND METHODS: HIV-positive ART-naïve adults eligible for ART initiation were prospectively recruited from October 2011 until March 2013. At inclusion, all patients submitted sputum for microbiological TB testing (smear microscopy, liquid culture and PCR). Virological suppression rates after six months of ART (VS; viral load <40 and <400 copies/mL) with regard to TB status was the primary outcome. The impact of HIV/TB co-infection on VS rates was determined by multivariate regression analysis. Mortality and retention in care were analyzed by proportional hazard models. RESULTS: Among 812 participants (TB 158; non-TB 654), 678 started ART during the follow-up period (TB 135; non-TB 543). Median CD4 cell counts at ART initiation were 161 cells/µL (interquartile range [IQR], 98-243) and 184 (IQR, 118-256) for TB and non-TB patients, respectively (p=0.05). No difference in retention in care between TB and non-TB patients was observed during follow-up; 25 (3.7%) patients died and 17 (2.5%) were lost to follow-up (p=0.30 and p=0.83, respectively). Overall rates of VS at six months were 72.1% (<40 copies/mL) and 88.7% (<400 copies/mL), with similar results for subjects with and without TB co-infection (<40 copies/mL: 65/92 (70.7%) vs. 304/420 (72.4%), p=0.74; <400 copies/mL: 77/92 (83.7%) vs. 377/420 (89.8%), p=0.10, respectively). CD4 cell count increase during treatment was 87 (IQR, 26-178) and 103 cells/µL (IQR, 38-173) for TB and non-TB patients, respectively, with no significant difference between the two groups (p=0.49). CONCLUSIONS: High rates of VS were achieved in adults receiving ART at Ethiopian health centres managed by non-physician clinicians, with no significant difference with regard to TB co-infection. These findings demonstrate the feasibility of combined ART and anti-TB treatment at primary health care level in low-income countries. This study is registered with clinicaltrial.gov, NCT01433796.

Intensified tuberculosis case-finding in HIV-positive adults managed at Ethiopian health centers: diagnostic yield of Xpert MTB/RIF compared with smear microscopy and liquid culture.

BACKGROUND: Detection of active tuberculosis (TB) before antiretroviral therapy (ART) initiation is important, but optimal diagnostic methods for use in resource-limited settings are lacking. We assessed the prevalence of TB, evaluated the diagnostic yield of Xpert MTB/RIF in comparison with smear microscopy and culture, and the impact of Xpert results on clinical management in HIV-positive adults eligible for ART at health centers in a region of Ethiopia. METHODS: Participants were prospectively recruited and followed up at 5 health centers. Trained nurses collected data on socio-demographic characteristics, medical history and symptoms, and performed physical examination. Two paired morning sputum samples were obtained, and lymph node aspirates in case of lymphadenopathy. Diagnostic yield of Xpert MTB/RIF in sputum was compared with smear microscopy and liquid culture. RESULTS: TB was diagnosed in 145/812 participants (17.9%), with bacteriological confirmation in 137 (16.9%). Among bacteriologically confirmed cases, 31 were smear-positive (22.6%), 96 were Xpert-positive (70.1%), and 123 were culture-positive (89.8%). Xpert MTB/RIF increased the TB detection rate by 64 cases (47.4%) compared with smear microscopy. The overall sensitivity of Xpert MTB/RIF was 66.4%, and was not significantly lower when testing one compared with two samples. While Xpert MTB/RIF was 46.7% sensitive among patients with CD4 cell counts >200 cells/mm(3), this increased to 82.9% in those with CD4 cell counts ≤100 cells/mm(3). Compared with Xpert-positive TB patients, Xpert-negative cases had less advanced HIV and TB disease characteristics. CONCLUSIONS: Previously undiagnosed TB is common among HIV-positive individuals managed in Ethiopian health centers. Xpert MTB/RIF increased TB case detection, especially in patients with advanced immunosuppression. An algorithm based on the use of a single morning sputum sample for individuals with negative sputum smear microscopy could be considered for intensified case finding in patients eligible for ART. However, technical and cost-effectiveness issues relevant for low-income countries warrant further study.

High rates of virological suppression in a cohort of human immunodeficiency virus-positive adults receiving antiretroviral therapy in ethiopian health centers irrespective of concomitant tuberculosis.

BACKGROUND: Antiretroviral therapy (ART) initiation during treatment for tuberculosis (TB) improves survival in human immunodeficiency virus (HIV)/TB-coinfected patients. We compared virological suppression (VS) rates, mortality, and retention in care in HIV-positive adults receiving care in 5 Ethiopian health centers with regard to TB coinfection. METHODS: Human immunodeficiency virus-positive ART-naive adults eligible for ART initiation were prospectively recruited. At inclusion, all patients underwent microbiological investigations for TB (sputum smear, liquid culture, and polymerase chain reaction). Virological suppression rates after 6 months of ART (VS; viral load <40 and <400 copies/mL) with regard to TB status was the primary outcome. The impact of HIV/TB coinfection on VS rates was determined by multivariate regression analysis. Mortality and retention in care were analyzed by proportional hazard models. RESULTS: Among 812 participants (TB, 158; non-TB, 654), 678 started ART during the follow-up period (TB, 135; non-TB, 543). No difference in retention in care between TB and non-TB patients was observed during follow-up; 25 (3.7%) patients died, and 17 (2.5%) were lost to follow-up (P = .30 and P = .83, respectively). Overall rates of VS at 6 months were 72.1% (<40 copies/mL) and 88.7% (<400 copies/mL), with similar results for subjects with and without TB coinfection (<40 copies/mL: 65 of 92 [70.7%] vs 304 of 420 [72.4%], P = .74; <400 copies/mL: 77 of 92 [83.7%] vs 377 of 420 [89.8%], P = .10, respectively). CONCLUSIONS: High rates of VS can be achieved in adults receiving ART at health centers, with no significant difference with regard to TB coinfection. These findings demonstrate the feasibility of combined ART and anti-TB treatment in primary healthcare in low-income countries. CLINICAL TRIALS REGISTRATION: NCT01433796.

CD4 cell levels during treatment for tuberculosis (TB) in Ethiopian adults and clinical markers associated with CD4 lymphocytopenia.

BACKGROUND: The clinical correlations and significance of subnormal CD4 levels in HIV-negative patients with TB are unclear. We have determined CD4 cell levels longitudinally during anti-tuberculosis treatment (ATT) in patients, with and without HIV co-infection, and their associations with clinical variables. METHOD: Adults diagnosed with TB (maximum duration of ATT for 2 weeks, and with no history of antiretroviral therapy (ART) in HIV-positive subjects) were included consecutively in eight out-patient clinics in Ethiopia. Healthy individuals were recruited for comparison at one of the study health centers. Data on patient characteristics and physical findings were collected by trained nurses following a structured questionnaire at inclusion and on follow-up visits at 2 and 6 months. In parallel, peripheral blood CD4 cell levels were determined. The evolution of CD4 cell levels during ATT was assessed, and the association between clinical characteristics and low CD4 cell levels at baseline was investigated using regression analysis. RESULTS: In total, 1116 TB patients were included (307 HIV-infected). Among 809 HIV-negative patients, 200 (25%) had subnormal CD4 cell counts (<500 cells/mm(3)), with <350 cells/mm(3) in 82 (10%) individuals. CD4 cell levels increased significantly during the course of ATT in both HIV+ and HIV- TB-patients, but did not reach the levels in healthy subjects (median 896 cells/mm(3)). Sputum smear status, signs of wasting (low mid upper arm circumference (MUAC)), and bedridden state were significantly associated with low CD4 cell counts. CONCLUSION: A high proportion of Ethiopian TB patients have subnormal CD4 cell counts before starting treatment. Low CD4 cell levels are associated with smear positive disease and signs of wasting. The continuous increase of CD4 cell counts during the course of ATT suggest a reversible impact of active TB on CD4 cell homeostasis, which may be considered in interpretation of CD4 cell counts in HIV/TB co-infected subjects.