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Background. Tuberculosis is a major health concern in several countries, and effective diagnostic algorithms for use in human immunodeficiency virus (HIV)-positive patients are urgently needed. Methods. At prescription of antiretroviral therapy, all patients in 3 Mozambican health centers were screened for tuberculosis, with a combined approach: World Health Organization (WHO) 4-symptom screening (fever, cough, night sweats, and weight loss), a rapid test detecting mycobacterial lipoarabinomannan in urine (Determine TB LAM), and a molecular assay performed on a sputum sample (Xpert MTB/RIF; repeated if first result was negative). Patients with positive LAM or Xpert MTB/RIF results were referred for tuberculosis treatment. Results. Among 972 patients with a complete diagnostic algorithm (58.5% female; median CD4 cell count, 278/μL; WHO HIV stage I, 66.8%), 98 (10.1%) tested positive with Xpert (90, 9.3%) or LAM (34, 3.5%) assays. Compared with a single-test Xpert strategy, dual Xpert tests improved case finding by 21.6%, LAM testing alone improved it by 13.5%, and dual Xpert tests plus LAM testing improved it by 32.4%. Rifampicin resistance in Xpert-positive patients was infrequent (2.5%). Among patients with positive results, 22 of 98 (22.4%) had no symptoms at WHO 4-symptom screening. Patients with tuberculosis diagnosed had significantly lower CD4 cell counts and hemoglobin levels, more advanced WHO stage, and higher HIV RNA levels. Fifteen (15.3%) did not start tuberculosis treatment, mostly owing to rapidly deteriorating clinical conditions or logistical constraints. The median interval between start of the diagnostic algorithm and start of tuberculosis treatment was 7 days. Conclusions. The prevalence of tuberculosis among Mozambican HIV-positive patients starting antiretroviral therapy was 10%, with limited rifampicin resistance. Use of combined point-of-care tests increased case finding, with a short time to treatment. Interventions are needed to remove logistical barriers and prevent presentation in very advanced HIV/tuberculosis disease. [ABSTRACT FROM AUTHOR]

In this study, we analysed in a cohort of pregnant women followed for two years the proportion of women remaining at the same clinic, those who transferred to other clinics, and those lost to follow-up. The possible determinants of the loss to follow-up were also assessed in a setting of postpartum discontinuation based on CD4+ count. A total of 311 pregnant women received antiretroviral therapy from week 25 of gestational age until six months postpartum (end of breastfeeding period), or indefinitely if meeting the criteria for treatment (baseline CD4+ <350 cells/mm(3)). Twenty-four months after delivery, six women had died, 247 were in active follow-up, 21 had transferred to another antiretroviral therapy clinic and 37 were lost to follow-up (rate of loss to follow-up 13%, 95% CI 9.1-16.9%). The presence of a baseline CD4+ count above 350 cells/mm(3) was associated with a ten-fold higher risk of loss to follow-up after six months of delivery (hazard ratio: 9.8, 95% CI 2.2-42.7, for baseline CD4 >350 cells/mm(3) versus baseline CD4+ count below 350 cells/mm(3), p = 0.002). This finding suggests that discontinuation of drugs when the risk of transmission has ceased can have a negative impact on the retention in care of these women. [ABSTRACT FROM AUTHOR]

• Hypergammaglobulinemia is common in Malawian HIV-positive pregnant women. • Twenty-four months of antiretroviral therapy improved but did not normalize IgG anomalies. • The IgG2 isotype remained highly underrepresented. • The potential influence of immunoglobulin disorders should be considered when assessing the risk of infection in HIV-exposed infants. Hypergammaglobulinemia and anomalies in the IgG subclass distribution are common in HIV-infected individuals and persist even after many years of antiretroviral therapy (ART). The aim of this study was to investigate the IgG profile and dynamics in pregnant HIV-infected Malawian women in the Option B era. Thirty-seven treatment-naive women received ART from the third trimester of pregnancy to 6 months post delivery (end of the breastfeeding period). ART continuation (group C) or interruption (group I) was then decided on the basis of the CD4+ cell count at enrolment (>350 or ≤350/μl). Total IgG and IgG subclasses were determined in maternal serum using a nephelometric assay at baseline and at 6 and 24 months postpartum. At enrolment, 36/37 women had IgG levels >15 g/l and there was a predominance of the IgG1 isotype (more than 90%) in parallel with underrepresentation of IgG2 (5.0%). After 6 months of ART, both groups showed a significant median decrease in total IgG (−3.1 g/l in group I, −3.5 g/l in group C) and in IgG1 (−4.0 g/l and −3.6 g/l, respectively), but only a modest recovery in IgG2 levels (+0.16 in group I, +0.14 g/l in group C). At month 24, hypergammaglobulinemia was still present in 73.7% of women in group C, although a significant reduction was observed in total IgG level and in IgG1 and IgG3 subclasses (p < 0.0001 in all cases). IgG2 levels did not show any significant change. In group I at 24 months, total IgG and IgG subclasses had returned to levels comparable to those at baseline. The beneficial effects of 24 months of ART appear to be limited in the B-cell compartment, with an incomplete reduction of total IgG levels and no recovery of IgG2 depletion. A short ART period did not have significant effects on IgG abnormalities in women who interrupted treatment. [ABSTRACT FROM AUTHOR]

In sub-Saharan Africa the great majority of infants acquire Cytomegalovirus (CMV) infection within the first year of life. Maternal long-term antiretroviral therapy (ART) has been suggested to reduce the rate of CMV acquisition in HIV-exposed infants. In the present study serum samples collected at 6 months of age from HIV-exposed and HIV-unexposed infants were analyzed for the presence of CMV DNA (with CMV positivity defined by levels of CMV DNA > 1000 UI/ml). Twenty out of 58 (34.5%) infants had CMV DNA > 1000 UI/ml. There was no difference in the prevalence of CMV viremia between HIV-exposed and -unexposed infants [33.3% (15/45) vs 38.5% (5/13), respectively, P = 0.488]. In the HIV-exposed group, mothers of CMV-negative infants had received a longer antiretroviral treatment before delivery in comparison to mothers of CMV-positive infants (28 vs 3 months, P = 0.187). No differences in weights and lengths at birth, and at 1, 6 and 12 months were observed between CMV-positive and CMV-negative infants. In this study, the prevalence of CMV viremia at six months of age was high in infants born to HIV-positive mothers receiving long-term ART, similar to that of HIV-unexposed infants. Considering the possible relevant impact of CMV on infant health, strategies for containment of the infection should be explored. [ABSTRACT FROM AUTHOR]