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Background: The seroprevalence of Brucella infection in sub-Saharan regions is high, and no recent data are available for Malawi, a country in which >60% of the population is involved in agropastoral activity. Aim: To evaluated the seroprevalence of Brucella in a cohort of HIV-positive pregnant women, living in an urban setting in Malawi. Methods: Sera of 201 pregnant women were tested for Brucella IgG. The Rose Bengal Plate Test and Serum Agglutination Tube test were used to determine antibody titer. Results: Five out of 201 (2.48%) women show positivity to Brucella, consistent with a past exposition to the infection. All five women delivered healthy infants, but two of them reported previous abortion/stillbirths, with a higher rate than those of the rest of the cohort (40% vs. 21.5%). Conclusions: This is one of the first reports of exposure of pregnant women to Brucella infection in Malawi, providing evidence of Brucella occurrence in an urban setting. Control programs should be introduced to reduce its impact on animal and human health. [ABSTRACT FROM AUTHOR]

Background: In sub-Saharan African countries Epstein Barr virus (EBV) infection occurs in early childhood. We aim to investigate the factors associated with EBV acquisition and the impact of EBV infection on the humoral response to HBV vaccination in infants born from HIV-positive, antiretroviral-treated mothers in Malawi. Methods: A total of 149 HIV-exposed infants were included in this longitudinal study. EBV anti-VCA IgG were measured using an ELISA assay. The EBV seroconversion was correlated with the maternal viro-immunological conditions, with infant growth and immunological vulnerability, and with the humoral response to the HBV vaccine. Results: No infant was EBV-positive at 6 months (n. 52 tested). More than a third of infants (49/115 or 42.6 %) on study beyond 6 months seroconverted at 12 months. At 24 months, out of 66 tested infants, only 13 remained EBV-uninfected, while 53 (80.3 %) acquired EBV infection, rising the total proportion of EBV seroconversion to 88.7 % (102/115 infants). EBV seroconversion was significantly associated with a low maternal educational status but had no impact on infant growth or vulnerability to infections. Reduced HBsAb levels and accelerated waning of antibodies were associated with early EBV seroconversion. Conclusions: We found a heterogeneous timing of acquisition of EBV with the majority of infants born from HIV + mothers acquiring infection after 6 months. Anti-HBs levels were lower and appeared to wane faster in infants acquiring EBV infection. [ABSTRACT FROM AUTHOR]

Background: Maternal antibodies are key components of the protective responses of infants who are unable to produce their own IgG until 6 months of life. There is evidence that HIV-exposed uninfected children (HEU) have IgG levels abnormalities, that can be partially responsible for the higher vulnerability to infections in the first 2 years of the life of this population. This retrospective study aimed to characterize the dynamics in plasma levels of total IgG and their isotypes during the first 2 years of life in HEU infants exclusively breastfed through 6 months of age.Methods: Total IgG, IgG1, IgG2, IgG3 and IgG4 isotypes, and IgM and IgA plasma concentrations were determined by nephelometric methods in 30 Malawian infants born to HIV-positive women at month 1, 6 and 24 of life.Results: At 1-month infants had a median concentration of total IgG of 8.48 g/l, (IQR 7.57-9.15), with an overrepresentation of the IgG1 isotype (89.0% of total) and low levels of IgG2 (0.52 g/l, IQR, 0.46-0.65). Total IgG and IgG1 concentrations were lower at 6 months (- 2.1 and - 1.12 g/dl, respectively) reflecting disappearance of maternal antibodies, but at 24 months their levels were higher with respect to the reported reference values for age-matched pairs. Abnormal isotype distribution was still present at 24 months with IgG2 remaining strongly underrepresented (0.87 g/l, 7.5% of total IgG).Conclusion: HIV exposure during pregnancy and breastfeeding seems to influence the IgG maturation and isotype distribution that persist in 2-year old infants. [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.

Objectives: No data are available on bone metabolism in infants exposed to tenofovir during breastfeeding. We investigated bone metabolism markers in the first year of life in infants from mothers who received tenofovir, lamivudine and efavirenz during pregnancy and 12 months of breastfeeding in a national Option B+ programme in Malawi.Methods: Serum samples collected at 6 and 12 months in tenofovir-exposed infants and in a small sample of tenofovir-unexposed infants from the same clinical centre were analysed in batches for levels of bone-specific alkaline phosphatase (BAP; marker of bone formation) and of C-terminal telopeptide of type I collagen (CTX; marker of bone resorption).Results: Overall, 136 tenofovir-exposed infants were evaluated. No infant had at either timepoint CTX values above the upper normal limit, while most of them had at 6 and 12 months levels of BAP above the upper normal limit for the age range. Levels of bone markers showed no differences by gender and no association with growth parameters. Tenofovir-unexposed and -exposed children had similar mean levels of bone markers at 6 months (CTX: 0.62 versus 0.55 ng/mL, P = 0.122; BAP: 384 versus 362 U/L, P = 0.631).Conclusions: No significant association between treatment with tenofovir and CTX or BAP levels was found. The high levels of BAP, coupled to the normal levels observed for CTX, might reflect primarily skeletal growth. Potential negative effects of prolonged exposure to tenofovir through breastfeeding cannot however be excluded and longitudinal studies that evaluate bone mineralization status in children enrolled in Option B+ programmes are warranted. [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]

Objectives: To evaluate antiretroviral drug concentrations in mothers and infants enrolled under the Option B-Plus approach for the prevention of HIV mother-to-child transmission in Malawi and to assess the maternal virological response after 1 year of treatment.Patients and Methods: Forty-seven women and 25 children were studied. Mothers were administered during pregnancy a combination of tenofovir, lamivudine and efavirenz and continued it during breastfeeding (up to 2 years) and thereafter. Drug concentrations were evaluated in mothers (plasma and breast milk) at 1 and 12 months post-partum and in infants (plasma) at 6 and 12 months of age. Drug concentrations were determined using an LC-MS/MS validated methodology.Results: In breast milk, tenofovir concentrations were very low (breast milk/maternal plasma ratio = 0.08), while lamivudine was concentrated (breast milk/plasma ratio = 3) and efavirenz levels were 80% of those found in plasma. In infants, median levels at 6 months were 24 ng/mL tenofovir, 2.5 ng/mL lamivudine and 86.4 ng/mL efavirenz. At month 12, median levels were below the limit of quantification for the three drugs. No correlation was found between drug concentrations and laboratory parameters or indices of growth. HIV-RNA >1000 copies/mL was seen at month 1 in 15% of the women and at month 12 in 8.5%. Resistance was found in half of the women with detectable viral load.Conclusions: Breastfeeding infants under Option B-Plus are exposed to low concentrations of antiretroviral drugs. With this strategy, mothers had a good virological response 1 year after delivery. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to determine the prevalence of drug resistance mutations among HIV-positive women in Malawi 18 months after discontinuing nevirapine-based ART for the prevention of mother-to-child transmission.Patients and Methods: HIV-infected antiretroviral-naive (except for single-dose nevirapine) pregnant Malawian women receiving a nevirapine-based triple antiretroviral regimen from Week 25 of gestation until 6 months of breastfeeding were included in this analysis. Drug resistance was assessed in HIV-DNA 24 months post-partum and at baseline (before the initiation of treatment). In patients with resistance, the presence of mutations was also evaluated in the corresponding plasma samples.Results: Seven out of 42 (16.7%) women studied had archived drug resistance at Month 24 [six cases had NNRTI-associated mutations and two cases the M184I mutation]. In four cases, resistance mutations were already present at baseline (all NNRTI mutations). In three cases, there was an emergence of 'new' resistance (also present in the plasma in one case). Of the 35 women without resistance mutations at Month 24, only one subject had resistance mutations at baseline. Baseline resistance was significantly more common among women with mutations at 24 months compared with those harbouring a WT virus (4/7 versus 1/35, P < 0.001).Conclusions: Among women who had discontinued drugs 6 months post-partum, only 3/42 (7.1%) had accumulated new resistance mutations in HIV-DNA 2 years after delivery. These findings are reassuring in terms of the safety of the Option B strategy for the prevention of HIV mother-to-child transmission. [ABSTRACT FROM AUTHOR]

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]

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.

Background: HIV-exposed uninfected (HEU) infants show a high rate of morbidity. We aimed to investigate on biomarkers of immune activation/microbial translocation in HEU infants, evaluating the impact that infections/malnutrition can have on biomarker levels during the first year of life., Methods: Clinical data of 72 Malawian infants were recorded monthly and correlated with levels of soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP) and intestinal fatty acid-binding protein (I-FABP), analyzed longitudinally., Results: Levels of sCD14 and LBP showed a significant age-related increase. Higher levels of LBP (19.4 vs. 15.2 μg/ml) were associated with stunting, affecting 30% of the infants. The association remained statistically significant after adjusting for cytomegalovirus acquisition, malaria and respiratory infections (p = 0.031). I-FABP levels were significantly increased in infants experiencing gastrointestinal infections (1442.8 vs. 860.0 pg/ml, p = 0.018)., Conclusion: We provide evidence that stunting is associated with an enhanced inflammatory response to microbial products in HEU children, suggesting that malnutrition status should be taken into consideration to better understand the alteration of the immune profile of HEU infants living in poor socioeconomic settings., (© The Author(s) [2019]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

HIV-infected patients have increased risk of noncommunicable diseases (NCDs). HIV+ patients in Africa are experiencing growing comorbidities due to increase in life expectancy and long-time antiretroviral therapy (ART). HIV prevalence in Malawi is one of highest in the world (10.8% in women and 6.4% in men); few data are available about NCDs epidemiology in HIV+ elderly patients in Malawi. A retrospective analysis of routine medical records in 14 health centers run by Disease Relief through Excellent and Advanced Means (DREAM) program in Malawi was carried out. All HIV+ patients aged >40 years in care in the period January 01, 2017-December 31, 2018 were included. Clinical and laboratory features were collected in the last visit of the study period. Files from 7,071 patients (62.1% women) in ART were analyzed, 362 (5.1%) were aged >65 years. Median time on ART was 98.9 (64.8-118.0) months; median body mass index, haemoglobin (HB), and CD4 count were, respectively, 21.63 kg/m 2 (19.5-24.5), 13 mg/dL (12-14), and 457 cell/mm 3 (328-613). Elderly patients >65 years were more likely to be malnourished (odds ratio [OR] = 2.0, confidence interval [CI]: 1.54-2.59), diagnosed with arterial hypertension (OR = 2.5, CI: 1.94-3.43), affected with diabetes (OR = 2.7, CI: 1.25-6.22), have macrocytic anemia (OR = 2.5, CI: 2.00-3.35), and increased serum creatinine (OR = 1.5, CI: 1.03-2.43]). Other factors were associated with NCD burden, but age remained always independently related. Two concomitant chronic conditions in addition to HIV were present in 19.2% (66/343) of elderly people and 5.2% (338/6.454) of patients aged <65 years (OR = 4.3, CI: 3.22-5.76). Some associations were observed: nevirapine (NVP) was associated with kidney disease (OR = 1.5, CI: 1.22-2.06), NVP and protease inhibitor (PI) with hypertension (OR = 2.79, CI: 2.16-3.35 and OR = 2.15, CI: 1.52-3.02), azidothymidine (AZT) with macrocytic anemia (OR = 15.6, CI: 13.18-18.68). NVP, AZT, and duration of any ART >3 years were associated with the presence of two or more comorbidities (OR = 2.1 1.54-2.96, OR = 2.6 1.87-3.71, and OR = 1.7 1.12-2.84). Our data show the burden of NCDs in aging HIV+ patients in Malawi. The expansion of HIV treatment programs will require special attention to such comorbidities in elderly patients.

Objectives: 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., Methods: 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., Results: At enrolment, 36/37 women had IgG levels >15g/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 (-3.1g/l in group I, -3.5g/l in group C) and in IgG1 (-4.0g/l and -3.6g/l, respectively), but only a modest recovery in IgG2 levels (+0.16 in group I, +0.14g/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., Conclusions: 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., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of this study was to assess the immune response to HBV vaccine in HIV-exposed infants and to correlate it to HBV infection acquisition. Protective anti-HBs levels (>10 mIU/mL) were found in 54/58 (93.2%) infants at 6 months, 126/144 (87.5%) at 12 months and 141/176 (80.1%) children at 24 months. HBV infection (seven children were HBsAg + at Month 24) occurred also in the presence of levels above 10 mIU/mL. Our findings indicate limited impact of HIV exposure on anti-HBV immune response, but suggest that levels >10 mIU/mL may be required to confer protection in this context., (© 2018 Wiley Periodicals, Inc.)

Combination antiretroviral therapy has been shown to reduce HIV transmission and incident infections. In recent years, Malawi has significantly increased the number of individuals on combination antiretroviral drugs through more inclusive treatment policies. Using a retrospective observational cohort design, records with HIV test results were reviewed for pregnant women attending a referral hospital in Malawi over a 5-year period, with viral load measurements recorded. HIV prevalence over time was determined, and results correlated with population viral load. A total of 11 052 women were included in this analysis, with 440 (4.1%) HIV infections identified. HIV prevalence rates in pregnant women in Malawi halved from 6.4% to 3.0% over 5 years. Mean viral loads of adult patients decreased from 120 000 copies/mL to less than 20 000 copies/mL. Results suggest that community viral load has an effect on HIV incidence rates in the population, which in turn correlates with reduced HIV prevalence rates in pregnant women., (© The Author(s) 2015.)

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.

Background: HIV infection is a major contributor to maternal mortality in resource-limited settings. The Drug Resource Enhancement Against AIDS and Malnutrition Programme has been promoting HAART use during pregnancy and postpartum for Prevention-of-mother-to-child-HIV transmission (PMTCT) irrespective of maternal CD4 cell counts since 2002., Methods: Records for all HIV+ pregnancies followed in Mozambique and Malawi from 6/2002 to 6/2010 were reviewed. The cohort was comprised by pregnancies where women were referred for PMTCT and started HAART during prenatal care (n = 8172, group 1) and pregnancies where women were referred on established HAART (n = 1978, group 2)., Results: 10,150 pregnancies were followed. Median (IQR) baseline values were age 26 years (IQR:23-30), CD4 count 392 cells/mm(3) (IQR:258-563), Viral Load log10 3.9 (IQR:3.2-4.4), BMI 23.4 (IQR:21.5-25.7), Hemoglobin 10.0 (IQR: 9.0-11.0). 101 maternal deaths (0.99%) occurred during pregnancy to 6 weeks postpartum: 87 (1.1%) in group 1 and 14 (0.7%) in group 2. Mortality was 1.3% in women with

HIV/HBV co-infection is highly prevalent in sub-Saharan Africa. The aim of this study was to determine if the use of triple combination lamivudine-containing prophylaxis for the prevention of mother-to-infant HIV transmission was associated with the emergence of lamivudine HBV mutations. The study included 21 pregnant co-infected women in Malawi who received either zidovudine or stavudine plus lamivudine and nevirapine from week 25 of gestation until 6 months after delivery or indefinitely if they met the criteria for treatment (CD4+ <350/mm(3)). HBV-DNA was determined using the Roche COBAS assay. Resistance mutations were assessed by the Trugene assay (Siemens Diagnostics). At baseline 33% of the women were HBeAg positive and had HBV-DNA > 10(4) IU/ml. Median CD4 count was 237 cells/mm(3) and median HIV-RNA was 3.8 log(10) copies/ml. After a median of 259 days of treatment, HBV-DNA was detectable in 9 out of 21 patients (42.8%). In three cases the HBV-DNA level was >10(4) IU/ml. Resistance mutations (M204I in five cases and L180M + M204I/V in one case) were present in 6 (28.6%) patients. Women with a resistant virus had significantly higher baseline HBV-DNA levels than those not developing resistance (1.1 × 10(7) IU/ml vs. 20.8 IU/ml, P = 0.022). Levels of ALT and AST were higher in women with resistant viruses compared to those retaining a wild-type virus. A high rate of lamivudine resistance was seen in this cohort of pregnant women. Follow-up of these patients will clarify if the presence of resistance has a significant impact on liver disease., (Copyright © 2012 Wiley Periodicals, Inc.)

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 26565 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.

Infant malnutrition in sub-Saharan Africa is a public health priority and a challenge in high HIV prevalence areas. The Drug Resources Enhancement Against AIDS and Malnutrition program, with multiple medical centers in Sub-Saharan Africa, developed an innovative intervention for the surveillance and control of malnutrition. In a pilot initiative, 36 HIV-exposed children were evaluated at baseline upon presentation for malnutrition and at six months post- treatment. Parameters included HIV-free survival, nutritional status and change in diet. Food diary data was entered and processed using the Nutrisurvey (WHO) software. At 6 months post-intervention, a significant improvement in anthropometric parameters was noted. Slowing of linear growth was observed in patients with malaria with a mean gain in centimetres of 4.4 ± 1.7 as compared to 5.6 ± 1.7 in children with no malaria, p < 0.048 (CL 95%: -2.32, -0.01). Dietary diversity scores increased from 5.3 ± 1.9 to 6.5 ± 1.3, p < 0.01 at 6 months. A significant increase (+25%, p < 0.02) in the number of children eating fish meals was noted. Our pilot data describes positive outcomes from a rehabilitative nutritional approach based on use of local foods, peer education, anthropometric and clinical monitoring in areas of high food insecurity. The relationship between malaria and linear growth retardation requires further investigation.

Background: Limited information is available on antiretroviral concentrations in women/infant pairs receiving prophylaxis for breastfeeding transmission of HIV and on the relationship between drug levels and the virological and haematochemistry parameters., Methods: Patient population included HIV-positive pregnant women receiving antiretroviral prophylaxis from gestational week 25 until 6 months after delivery and their breastfed infants. Blood and breast milk samples were collected at delivery, and at months 1, 3 and 6 postpartum. Drug concentrations were measured by liquid chromatography-mass spectrometry., Results: Overall, 66 women were studied: 29 received zidovudine (ZDV), lamivudine (3TC) and nevirapine (NVP), 28 stavudine (d4T), 3TC and NVP, and 9 ZDV, 3TC and lopinavir/ritonavir (LPV/r). Women who received >9 weeks of pre-partum prophylaxis were significantly more likely to have an undetectable viral load both in plasma and in breast milk at delivery. No emergence of resistance mutations was observed in breast milk. Breast milk/plasma concentration ratios were 0.6 for ZDV, 3TC and NVP, 1.0 for d4T and 0.4 for LPV/r. Only NVP reached significant levels in the infants. No correlation with any adverse events, including infant anaemia, was observed with drug concentrations. Two infants who acquired HIV infection had non-nucleoside reverse transcriptase inhibitor mutations at month 6., Conclusions: Maternal administration of these three regimens up to 6 months postpartum was effective and safe for both mothers and infants. No significant correlation was found between drug concentrations and infant haematological parameters, supporting the hypothesis that other factors may contribute to the development of anaemia in these settings.

Objective: To evaluate pregnancy outcomes in a cohort of HIV-infected women receiving triple antiretroviral therapy (ART) for prevention of mother-to-child-transmission., Methods: A retrospective cohort study with review of records of 3273 HIV-positive women receiving prenatal care in Malawi and Mozambique from July 2005 to December 2009 was conducted in Drug Resource Enhancement Against AIDS and Malnutrition (DREAM) centers. Patients were offered nevirapine-based triple ART initiated in pregnancy until 6 months postpartum. Main outcome measures were maternal mortality, abortion/stillbirth, prematurity, and low birth weight., Results: Maternal mortality was 1.2% (42/3273): 7.4% in 68 women with no antenatal ART and 0.7% in 1370 with at least 90 days of antenatal ART [P < 0.001; odds ratio (OR) 0.29 (95% confidence interval [CI] 0.14-0.96]. Abortion/stillbirth was 5.2% (169/3273): 26.5% in 68 women with no ART and 5.0% in 1370 women with at least 90 days of antenatal ART [P < 0.001; OR 0.39 (95% CI 0.27-0.57)]. Prematurity was 19.1%: 70% in 10 women with no antenatal ART and 8.5% in 1330 women with at least 90 days of antenatal ART [P < 0.001; OR 0.15 (95% CI 0.14-0.19)]. Low birth weight was 11.5% (57/496) and not associated with ART duration. The protective effect of antenatal ART against mortality, fetal demise, and prematurity was independent of CD4 strata. Multivariate analysis for BMI, CD4 cell count, virus load, days in care, predelivery length of ART, and hemoglobin demonstrated an independent association between predelivery length of ART and CD4 with maternal mortality, abortion/stillbirth, and prematurity. ART toxicities were infrequent (5.2%)., Conclusion: Antenatal triple ART reduces adverse pregnancy outcomes in HIV-infected women.

Objectives: To evaluate the effect of extended antenatal triple antiretroviral therapy (ART) on infant outcomes., Design: Retrospective cohort study using pooled data from health clinics in Malawi and Mozambique from July 2005 to December 2009., Methods: Computerized records of 3273 HIV-infected pregnant women accessing Drug Resource Enhancement Against AIDS and Malnutrition centers were reviewed. ART regimens consisted of nevirapine-based HAART as of 14-25 weeks gestation until 6 months postpartum. Infant infection was determined at 1, 6 and 12 months of age by branched DNA., Results: A total of 3071 pregnancies resulted in 3148 live births. Lost to follow-up, infant deaths and HIV-1 infection rates at 1 and 12 months were 1.3 and 11.5, 0.8 and 6.7 and 0.8 and 2.0, respectively. Infant HIV-1-free survival at 12 months was 92.5%. Mother-to-child transmission and/or infant deaths correlated with length of maternal antenatal ART by multivariate analysis at 1, 6 and 12 months: 14% in women with more than 30 days of triple antenatal ART and 6.9% in mothers receiving at least 90 days of antenatal ART, P = 0.001. Fifty percent of 54 episodes of transmission occurred in women with higher CD4 cell counts (>350 cells/μl). Infant mortality was 67/1000, lower than background rates (78-100/1000). Growth failure (weight-for-age Z score <-2) was present in 8% of infants around birth, 6% at 6 months, 23% at 12 months (lower than country-specific rates)., Conclusion: Extended antenatal ART is protective against adverse infant outcomes up to 12 months of age even in children born to mothers with higher CD4 cell counts.

The response to treatment and risk factors for early mortality following initiation of combination antiretrovirals(ARVs) in a cohort of African patients are described in a retrospective cohort design. Medical history, laboratory parameters, and mortality data were reviewed for patients initiating ARVs in 12 clinical centers in Mozambique, Tanzania, and Malawi. Among 3456 HIV-1-infected patients who received ARVs for more than 6 months, at baseline 72% had WHO clinical stages 3/4, 7% had a viral load 400 copies/ml, and 38% had a CD4 cell count >200/microl. One year later, 78% had undetectable virus loads and 79% had CD4 cell counts >200 cells/mm3. In the first year of HAART 260 deaths occurred (97 per 1000 person/years) with mortality peaking in the first 3 months. The highest mortality was observed in patients with low BMI, low hemoglobin levels, and CD4 values <200 cells/microl at baseline. Mortality rates following initiation of HAART are higher in patients in resource-limited areas, particularly in the first 90 days following treatment initiation.HAART initiated at higher CD4 cell count levels, especially among malnourished and/or anemic patients, will carry significant public health impact.