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• 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]

The article discusses research that examined the association of hepatitis E virus (HEV) prevalence with HIV infection in sub-Saharan Africa, focusing on pregnant Malawian women. Topics covered include the seroprevalence of hepatitis E during pregnancy, the rate of new HEV infections 2 years after delivery, and HEV prevalence in HIV-exposed children in the endemic area.

Background Virtually all HIV-infected women in sub-Saharan Africa have evidence of Cytomegalovirus (CMV) infection and levels of specific anti-CMV IgG have been suggested to represent more intense reactivation of subclinical infection. Studies have also shown direct influence of CMV on lymphocytes. Objective The aim of this study was to determine if levels of anti-CMV specific antibodies could impact on the immunological response to antiretroviral treatment (ART) in HIV-infected pregnant women. Study design CMV-specific IgG were measured in HIV-infected pregnant women at 26 weeks of gestation (before ART initiation). Women received ART until 6 months postpartum or indefinitely according to local guidelines at the time of the study. Immunological and virological responses were assessed 6 months and 24 months after delivery. Results A total of 81 women were studied. At baseline high levels (above the median) of specific IgG were associated to a low CD4+ cell count (P< 0.001), a high viral load (P = 0.003), and to an older age (P = 0.051). In a multivariate model adjusting for baseline CD4+ count, baseline viral load and age, the presence of low levels of CMV IgG was the only independent predictor of a a CD4+ count above 500/mm 3 24 months after delivery among women on continuous therapy. Conclusions In this cohort, levels of CVM IgG had a significant influence on the immunological response to ART, adding information to the known impact of CMV infection in the HIV-positive population, and underlining the need of new strategies to contain the infection. [ABSTRACT FROM AUTHOR]

Background: We describe the accumulation of HIV-1 drug resistance and its effect on the activity of next-line components in patients with virological failure (HIV-1 RNA >1000 copies/mL) after 1 year (t1) of first-line antiretroviral therapy (ART) not switching to second-line drugs for one additional year (t2) in low-middle income countries (LMIC).Methods and Results: We selected 48 patients from the DREAM cohort (Maputo, Mozambique); their median pre-ART CD4+ cell count was 165 cells/μl. At t1 patients were receiving ART since a median of 12.2 months (mainly zidovudine/lamivudine/nevirapine), their median HIV RNA was 3.8 log10 copies/mL, 43 (89.6%) presented at least one resistance-associated mutation (RAM), most frequently for lamivudine/emtricitabine, nevirapine and efavirenz. Resistance to tenofovir, was 10% at 1 year and higher than 20% at 2 years, while projection at 3 years was >30%. At t2, 42 (89.4%) had a predicted low-level or higher resistance to at least 1 s-line drug. At t1, the frequency of RAM in patients with a lower adherence to pharmacy appointments (<95%) was significantly lower (12/20, 60% for NRTI and 14/20, 70% for NNRTI) than in those with a better adherence (26/28, 92.8% for NRTI and 25/28, 89.3% for NNRTI) (OR 0.12, 95% CI 0.02-0.63, p = 0.012 and OR 0.28, 95% CI 0.06-1.29, p = 0.103, respectively). Overall thymidine analogue mutations (TAMs) accumulation rate was 0.32/year, 0.50/year in the subgroup with HIV RNA >10,000 copies/mL; NNRTI RAM accumulation rate was 0.15/year, 0.40/year in the subgroup with HIV RNA >10,000 copies/mL.Conclusions: While the activity of NNRTIs is compromised early during failure, tenofovir and zidovudine activity are reduced more frequently after 1 year of documented virological failure of thymidine analogue-based first-line ART, with RAMs accumulating faster in patients with higher viral loads. The present observation may help informing decisions on when to switch to a second line ART in patients on virological failure in LMIC. [ABSTRACT FROM AUTHOR]

Objectives To identify factors associated with detectable viral load and the emergence of drug resistance in a cohort of HIV-infected pregnant women in Malawi receiving antiretroviral combination regimens for the prevention of mother-to-infant transmission. Methods The study included 260 treatment-naive women who had received a three-drug nevirapine-based regimen from week 25 of gestational age until 6 months after delivery. HIV RNA was determined at month 6 and drug resistance was assessed if viral load was >50 copies/mL. Attendance at the scheduled follow-up visits was used as an indirect measure of treatment adherence. Results The rate of detectable HIV RNA at 6 months was 9.6% (25/260). The only significant predictor of this occurrence was the presence of ≥1 missed visit during follow-up (P = 0.012). Resistance was assessed in 19 of these women: 7 (37%) had a wild-type virus and the other 12 (63%) had resistance-associated mutations (nucleoside reverse transcriptase inhibitor, 7/12; non-nucleoside reverse transcriptase inhibitor, 11/12). Three of 12 cases (25%) in which mutations were detected had a viral load <1000 copies/mL. The emergence of resistance was not correlated with the presence of baseline mutations in either plasma or archived DNA. Conclusions In this cohort of women, detectable HIV RNA 6 months post-partum was infrequent and associated with low adherence to the treatment programme. Mutations were present in 63% of the women with detectable viral load at 6 months who had samples available for resistance testing. The impact of resistance on treatment re-initiation in women discontinuing drugs after the risk of transmission has ceased can be limited. [ABSTRACT FROM PUBLISHER]

Background:Optimized preventive strategies are needed to reach the objective of eliminating pediatric AIDS. This study aimed to define the determinants of residual HIV transmission in the context of maternal antiretroviral therapy (ART) administration to pregnant women, to assess infant safety of this strategy, and to evaluate its impact on maternal disease. Methodology/Principal Findings:A total of 311 HIV-infected pregnant women were enrolled in Malawi in an observational study and received a nevirapine-based regimen from week 25 of gestation until 6 months after delivery (end of breastfeeding period) if their CD4+ count was > 350/mm3 at baseline (n = 147), or indefinitely if they met the criteria for treatment (n. 164). Mother/child pairs were followed until 2 years after delivery. The Kaplan-Meier method was used to estimate HIV transmission, maternal disease progression, and survival at 24 months. The rate of HIV infant infection was 3.2% [95% confidence intervals (CI) 1.0-5.4]. Six of the 8 transmissions occurred among mothers with baseline CD4+ count > 350/mm3. HIV-free survival of children was 85.8% (95% CI 81.4-90.1). Children born to mothers with baseline CD4+ count < 350/mm3 were at increased risk of death (hazard ratio 2.6, 95% CI 1.1-6.1). Among women who had stopped treatment the risk of progression to CD4+ count < 350/mm3 was 20.6% (95% CI 9.2-31.9) by 18 months of drug discontinuation. Conclusions:HIV transmission in this cohort was rare however, it occurred in a significative proportion among women with high CD4+ counts. Strategies to improve treatment adherence should be implemented to further reduce HIV transmission. Mortality in the uninfected exposed children was the major determinant of HIV-free survival and was associated to maternal disease stage. Given the considerable proportion of women reaching the criteria for treatment within 18 months of drug discontinuation, life-long ART administration to HIV-infected women should be considered. [ABSTRACT FROM AUTHOR]

Universal human immunodeficiency virus (HIV) test-and-treat approaches have been evaluated in mathematical models. We developed a district-level model based on actual data from 26-patients in the Drug Resource Enhancement Against AIDS and Malnutrition Program in sub-Saharan Africa. Rapid decreases were observed in the incidence of HIV infection and population infectivity.Background. The use of antiretrovirals to reduce the incidence of human immunodeficiency virus (HIV) infection has been evaluated in mathematical models as potential strategies for curtailing the epidemic. Cohort data from the Drug Resource Enhancement Against AIDS and Malnutrition (DREAM) Program was used to generate a realistic model for the HIV epidemic in sub-Saharan Africa.Methods. Two combined stochastic models were developed: patient and epidemic models. Models were combined using virus load as a parameter of infectivity. DREAM data that assessed patient care in Mozambique and Malawi were used to generate measures of infectivity, survival, and adherence. The Markov chain prediction model was used for the analysis of disease progression in treated and untreated patients. A partnership model was used to assess the probability that an infected individual would transmit HIV.Results. Data from 26 565 patients followed up from January 2002 through July 2009 were analyzed with the model; 63% of patients were female, the median age was 35 years, and the median observation time was 25 months. In the model, a 5-fold reduction in infectivity (from 1.6% to 0.3%) occurred within 3 years when triple ART was used. The annual incidence of HIV infection declined from 7% to 2% in 2 years, and the prevalence was halved, from 12% to 6%, in 11 years. Mortality in HIV-infected individuals declined by 50% in 5 years. A cost analysis demonstrated economic efficiency after 4 years.Conclusions. Our model, based on patient data, supports the hypothesis that treatment of all infected individuals translates into a drastic reduction in incident HIV infections. A targeted implementation strategy with massive population coverage is feasible in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to conduct an assessment of the cost-effectiveness of using highly active antiretroviral therapy (HAART) in prevention of mother-to-child transmission (PMTCT) in Malawi. The cost-effectiveness of a PMTCT program implemented at Drug Resource Enhancement against Aids and Malnutrition-Project Malawi (DREAM-PM) health centres was analyzed. Results of the study showed the cost-effectiveness of using of HAART in a PMTCT programme in resource-limited settings.

The article examines how administering antiretroviral drugs during the last trimester of pregnancy and around the time of delivery can be effective in the reduction of HIV transmission from mother to child. The research indicates that treatment with highly active antiretroviral therapy (HAART) results in plasma concentrations in breast milk that can reduce HIV RNA levels significantly.