Early assessment of weight velocity can support frontline health workers in predicting malnutrition in HIV-exposed infants: preliminary results from a DREAM cohort in Malawi.

BACKGROUND: Children born to HIV-positive mothers are particularly susceptible to malnutrition. Currently, monitoring programs rely on punctual anthropometric measurements to assess child growth. Growth velocities could be an additional tool in identifying critical time windows for prevention and implementation of early intervention for malnutrition. METHODS: A retrospective analysis was conducted using data from 817 HIV exposed but uninfected children extracted from DREAM program database. By using the WHO reference for growth standards, patterns of weight velocity for different intervals of assessment from one to 18 months of age were explored. Odds ratios and multinomial logistic regressions between selected weight velocity Z-scores thresholds and successive malnutrition indices (at 6, 12, 18 months of age) were calculated. RESULTS: Weight velocity was above the standard mean in the first 3 months, then progressively declined over time. In children with normal nutritional status, significant risks of becoming malnourished (mild malnutrition - underweight [OR 10.8; 95% CI: 4.5-26], chronic malnutrition - stunting [OR 8.3; 95% CI: 2-34.9] and acute malnutrition - wasting [OR 11.7; 95% CI: 1.5-90.5]) started when weight velocity Z-scores <0, at all interval ages. Multinomial regression showed that in the first 6 months, the weight velocity decrements strongly impacted on underweight (OR 17.9; 95% CI: 4-80.7), while the risk of Stunting occurred later at 18 months (OR 8.7; 95% CI: 4.3-17.6), with highest impact at the lowest thresholds. CONCLUSIONS: The assessment of weight velocity Z-scores, coupled with the already validated malnutrition indices, can support frontline health workers in early prediction of child malnutrition and performing nutritional counselling in the context of HIV/AIDS and food insecurity.

Incidence and predictors of death, retention, and switch to second-line regimens in antiretroviral- treated patients in sub-Saharan African Sites with comprehensive monitoring availability.

BACKGROUND: Antiretroviral treatment programs in sub-Saharan Africa have high rates of early mortality and loss to follow-up. Switching to second-line regimens is often delayed because of limited access to laboratory monitoring. METHODS: Retrospective analysis was performed of a cohort of adults who initiated a standard first-line antiretroviral treatment at 5 public sector sites in 3 African countries. Monitoring included routine CD4 cell counts, human immunodeficiency virus RNA measures, and records of whether appointments were kept. Incidence and predictors of death, loss to follow-up, and switch to second-line regimens were analyzed by time-to-event approaches. RESULTS: A total of 3749 patients were analyzed; at baseline, 37.1% were classified as having World Health Organization disease stage 3 or 4, and the median CD4 cell count was 192 cells/mL. First-line regimens were nevirapine based in 96.5% of patients; 17.7% of patients attended <95% of their drug pickup appointments. During 4545 person-years of follow-up, mortality was 8.6 deaths per 100 person-years and was predicted by lower baseline CD4 cell count, lower hemoglobin level, and lower body mass index (calculated as weight in kilograms divided by the square of height in meters); more-advanced clinical stage of infection; male sex; and more missed drug pickup appointments. Dropouts (which accrued at a rate of 2.1 dropouts per 100 person-years) were predicted by a lower body mass index, more missed visits and missed drug pickup appointments, and later calendar year. Incidence of switches to second-line regimens was 4.9 per 100 person-years; increased hazards were observed with lower CD4 cell count and earlier calendar year at baseline. In patients who switched, virological failure was predicted by combined clinical and CD4 criteria with 74% sensitivity and 30% specificity. CONCLUSIONS: In an antiretroviral treatment program employing comprehensive monitoring, the probability of switching to second-line therapy was limited. Regular pickup of medication was a predictor of survival and was also strongly predictive of patient retention.

Increased infant human immunodeficiency virus-type one free survival at one year of age in sub-saharan Africa with maternal use of highly active antiretroviral therapy during breast-feeding.

BACKGROUND: Reduction of HIV-1 breast-feeding transmission remains a challenge for prevention of pediatric infections in Sub-Saharan Africa. Provision of formula decreases transmission but often increases child mortality in this setting. METHODS: A prospective observational cohort study of HIV-1 exposed infants of mothers receiving pre and postnatal medical care at Drug Resource Enhancement Against AIDS and Malnutrition centers in Mozambique was conducted. Live-born infants of HIV-1-infected women receiving medical care were enrolled. HIV-1 testing was performed at 1, 6, and 12 months of age using branched DNA. Mothers were counseled to breast-feed exclusively for 6 months and were provided HAART antenatally and postnatally for the first 6 months. Women with CD4 cell counts less than 350/cmm at baseline continued HAART indefinitely. RESULTS: Of 341 infants followed from birth, 313 mother-infant pairs (92%) completed 6 months and 283 (83%) completed 12 months of follow-up. HIV-1 diagnosis was ascertained in 287 infants (84%) including 4 who died. There were 8 cases of HIV-1 transmission: 4 of 341 (1.2%) at 1 month, 2 of 313 (0.6%) at 6 months, and 2 of 276 (0.7%) at 12 months (cumulative rate: 2.8%). Two mothers (0.6%) and 11 infants (3.2%) died. Maternal and infant mortality rates were 587 of 100,000 and 33 of 1000, while country rates are 1000 of 100,000 and 101 of 1000. HIV risk reduction was 93% and HIV-free survival at 12 months was 94%. CONCLUSIONS: Late postnatal transmission of HIV-1 is significantly decreased by maternal use of HAART with high infant survival rates up to 12 months of age.

Evaluating adherence to highly active antiretroviral therapy with use of pill counts and viral load measurement in the drug resources enhancement against AIDS and malnutrition program in Mozambique.

BACKGROUND: Maintaining treatment adherence among the growing number of patients receiving antiretroviral treatment in Africa is a dramatic challenge. The objective of our study was to explore the results of a computerized pill count method and to test the validity, sensitivity, and specificity of this method with respect to viral load measurement in an African setting. METHODS: We performed a prospective, observational study involving patients who received first-line highly active antiretroviral therapy in Mozambique from 1 April 2005 through 31 March 2006. Enrolled patients had received treatment for at least 3 months before the study. For defining treatment adherence levels, pill counts were used, and the results were analyzed with viral load measurements at the end of the observation period. RESULTS: The study involved 531 participants. During the 12 months of observation, 137 patients left the program or discontinued first-line therapy. Of the remaining 394 patients, 284 (72.1%) had >95% treatment adherence; of those 284 patients, 274 (96.5%) had a final viral load <1000 copies/mL. A Cox proportional hazards analysis revealed that the relationship between >95% treatment adherence and the final viral load was closer than that between >90% treatment adherence and viral load. CONCLUSIONS: Treatment adherence >95% maximizes the results of the nonnucleoside reverse-transcriptase inhibitor-based regimen. The pill count method appears to be a reliable and economic tool for monitoring treatment adherence in resource-limited settings.

Elimination of Mother-To-Child Transmission of HIV Infection: The Drug Resource Enhancement against AIDS and Malnutrition Model.

The Drug Resource Enhancement against AIDS and Malnutrition Program (DREAM) gathered professionals in the field of Elimination of HIV-Mother-To-Child Transmission (EMTCT) in Maputo in 2013 to discuss obstacles and solutions for the elimination of HIV vertical transmission in sub-Saharan Africa. During this workshop, the benefits of administrating combined antiretroviral therapy (cART) to HIV positive women from pregnancy throughout breastfeeding were reviewed. cART is capable of reducing vertical transmission to less than 5% at 24 months of age, as well as maternal mortality and infant mortality in both HIV infected and exposed populations to levels similar to those of uninfected individuals. The challenge for programs targeting eMTCT in developing countries is retention in care and treatment adherence. Both are intrinsically related to the model of care. The drop-out from eMTCT programs before cART initiation ranges from 33%-88% while retention rates at 18-24 months are less than 50%. Comprehensive strategies including peer-to-peer education, social support and laboratory monitoring can reduce refusals to less than 5% and attain retention rates approaching 90%. Several components of the model of care for reduction of HIV-1 MTCT are feasible and implementable in scale-up strategies. A review of this model of care for HIV eMTCT is provided.

Reduction of maternal mortality with highly active antiretroviral therapy in a large cohort of HIV-infected pregnant women in Malawi and Mozambique.

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

Nutritional rehabilitation of HIV-exposed infants in Malawi: results from the drug resources enhancement against AIDS and malnutrition program.

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.

Correlation between HIV-1 viral load quantification in plasma, dried blood spots, and dried plasma spots using the Roche COBAS Taqman assay.

BACKGROUND: The use of simplified methods for viral load determination could greatly increase access to treatment monitoring of HIV patients in resource-limited countries. OBJECTIVE: The aim of the present study was to optimize and evaluate the performance of the Roche COBAS Taqman assay in HIV-RNA quantification from dried blood spots (DBS) and dried plasma spots (DPS). STUDY DESIGN: EDTA blood samples from 108 HIV-infected women were used to prepare 129 DBS and 76 DPS on Whatman 903 card. DBS and DPS were stored at -20 degrees C. HIV-1 RNA was extracted from DBS/DPS using the MiniMAG system (bioMerieux). Amplification and detection were performed using the Roche COBAS TaqMan assay. Plasma viral load results were used as standard. RESULTS: There was a high correlation between measures of viral load in plasma and in DBS/DPS (r=0.96 and 0.85 respectively, P<0.001). Overall, viral load values in DBS and DPS tended to be lower than in plasma with mean (SD) differences of 0.32 log(0.22) for DBS and of 0.35 (0.33) for DPS. Detection rates were 96.4% for DBS and 96.1% for DPS in samples with corresponding plasma values >3.0 log copies/ml. Samples with HIV-RNA below 50 copies/ml were correctly identified in 18/19 DBS and in 7/7 DPS. CONCLUSIONS: Both DBS and DPS provided results highly correlated to the plasma values. High detection rate was obtained with both DBS and DPS when HIV-RNA was >3.0 log copies/ml. Our results support the use of DBS/DPS to detect virologic failure in resource-limited settings.

Comparison of HIV type 1 sequences from plasma, cell-free breast milk, and cell-associated breast milk viral populations in treated and untreated women in Mozambique.

We analyzed the sequences of the HIV viral populations obtained from plasma, cell-free breast milk, and breast milk cells of HAART-treated (23) and untreated (30) HIV-infected women to obtain information about the origin of the breast milk virus. Sequence analyses of viruses were performed using the TruGene HIV-1 assay. Direct sequences of the reverse transcriptase (RT) and protease (PR) genes were analyzed using the Phylip 3.68 suite of sequence analysis program and pairwise evolutionary distances were calculated with the Kimura two parameter model for estimation of distances. We found that the genetic distances between the plasma and the cell-free breast milk viruses and between the cell-free and cell-associated breast milk viruses for RT were higher in HAART-receiving women than in untreated women, suggesting viral evolution under selective drug pressure in breast milk. Our data support the hypothesis of the presence of an actively replicating viral population in the breast milk compartment, distinct from that present in plasma.

Single-nucleotide polymorphisms in human beta-defensin-1 gene in Mozambican HIV-1-infected women and correlation with virologic parameters.

We analyzed single nucleotide polymorphisms in the 5'-untranslated region (-44C/G and -52G/A) of the beta-defensin-1 gene in 78 Mozambican HIV-1-infected mothers. We observed significantly lower levels of HIV-1 RNA in breast milk, but not in plasma, in women with the -52GG genotype versus women with the -52GA and -52AA genotypes, supporting the hypothesis that different expression of beta-defensins could have an impact on viral replication in breast milk.

Excessive early mortality in the first year of treatment in HIV type 1-infected patients initiating antiretroviral therapy in resource-limited settings.

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.

Triple antiretroviral prophylaxis administered during pregnancy and after delivery significantly reduces breast milk viral load: a study within the Drug Resource Enhancement Against AIDS and Malnutrition Program.

BACKGROUND: The administration of antiretroviral therapy to lactating women could represent a possible strategy to reduce postnatal HIV transmission. In this study, we assessed the effect of antiretroviral treatment on breast milk viral load and determined plasma and breast milk drug concentrations in pregnant women receiving highly active antiretroviral therapy (HAART). METHODS: We studied 40 women receiving zidovudine, lamivudine, and nevirapine from 28 weeks of gestation to 1 month postpartum (group A) and 40 untreated pregnant women (group B). Blood and breast milk samples were collected at delivery and 7 days postpartum. RESULTS: Women in group A had received a median of 85 days of therapy before delivery. Median breast milk concentrations of nevirapine, lamivudine, and zidovudine were 0.6, 1.8, and 1.1 times, respectively, those in maternal plasma. HIV RNA levels in breast milk were significantly lower in group A than in group B (median of 2.3 vs. 3.4 log at delivery and 1.9 vs. 3.6 log at day 7; P < 0.001 for both comparisons). CONCLUSIONS: Antiretroviral drugs administered during the last trimester of pregnancy and after delivery reach levels similar to or higher than plasma concentrations in breast milk and can significantly reduce HIV RNA levels. Our data support the potential role of maternal HAART prophylaxis in reducing the risk of breast-feeding-associated transmission.