NCT00993031.

Objective Combination antiretroviral therapy (ART) is now the global standard for HIV-infected pregnant and breastfeeding women at all CD4 cell counts. We compared the efficacy and safety of an efavirenz versus lopinavir/ritonavir regimen for HIV-infected pregnant women initiating ART in rural Uganda. Design Randomized clinical trial. Methods We performed a planned secondary analysis comparing viral load suppression (HIV-1 RNA ≤400 copies/ml), safety, and HIV transmission to infants in a trial designed to test the hypothesis that lopinavir/ritonavir- versus efavirenz-based ART would reduce placental malaria (PROMOTE, ClinicalTrials.gov, NCT00993031). HIV-infected, ART-naïve pregnant women at 12–28 weeks gestation and any CD4 cell count were randomized. ART was provided and participants were counseled to breastfeed for one year postpartum. Results The median age of the 389 study participants was 29 years; median CD4 cell count was 370 cells/mm3. At delivery, virologic suppression was 97.6% in the efavirenz arm and 86.0% in the lopinavir/ritonavir arm, p <0.001. At 48 weeks postpartum, 91.0% of women on efavirenz and 88.4% on lopinavir/ritonavir had viral suppression, p = 0.49. Grade 1 or 2 gastrointestinal adverse events were higher among women on lopinavir/ritonavir versus efavirenz. Only two infants acquired HIV (both in the lopinavir/ritonavir arm) and HIV-free infant survival was similar between study arms: 92.9% (lopinavir/ritonavir) versus 97.2% (efavirenz), p = 0.10. Conclusions Virologic suppression at delivery was higher with an efavirenz- versus lopinavir/ritonavir-based regimen. However, women in both arms achieved high levels of virologic suppression through one year postpartum and the risk of transmission to infants was low.

Objectives Household food insecurity may be a barrier to both optimal maternal nutritional status and infant feeding practices, but few studies have tested this relationship quantitatively, and never among HIV-infected individuals. We therefore explored if greater household food insecurity was associated with poorer maternal nutritional status, shorter duration of exclusive breastfeeding (EBF) and fewer animal-source complementary foods. Methods We assessed these outcomes among 180 HIV-infected pregnant and breastfeeding (BF) women receiving combination antiretroviral therapy in the PROMOTE trial (NCT00993031), a prospective, longitudinal cohort study in Tororo, Uganda. Results Household food insecurity was common; the prevalence of severe, moderate, and little to no household hunger was 7.3%, 40.5%, and 52.2%, respectively. Poor maternal nutritional status was common and women in households experiencing moderate to severe household hunger (MSHH) had statistically significantly lower BMIs at enrollment (21.3 vs 22.5, p<0.01) and prior to delivery (22.6 vs. 23.8, p<0.01). However, MSHH was not associated with maternal BMI or gestational weight gain in multivariate models. The prevalence (95% CI) of EBF at 6 months was 66.4% (59.0%-72.8%), and the proportion of women breastfeeding at 12 months was 80.0% (73.0%-85.3%).MSHH was not associated with EBF at 6 months or breastfeeding at 12 months. However, among those women still EBF at 4 months (81.0% of population), those experiencing MSHH were significantly more likely to cease EBF between 4 and 6 months (aHR: 2.52, 95% CI 1.03-6.19). Conclusions Interventions addressing household food insecurity, maternal malnutrition and suboptimal breastfeeding practices are urgently needed.

Background Protease inhibitor-based antiretroviral therapy (ART) has been associated with preterm birth in some studies. We examined risk factors for preterm birth among women randomized to lopinavir/ritonavir- or efavirenz-based ART. Methods This was a planned secondary analysis of the PROMOTE-Pregnant Women and Infants Study, an open-label, randomized controlled trial comparing the risk of placental malaria among HIV-infected, ART-naïve pregnant Ugandan women assigned to initiate lopinavir/ritonavir- or efavirenz-based ART at 12 to 28 weeks gestation. Gestational age was determined based on last menstrual period and ultrasound biometry. All women received bednets and trimethoprim-sulfamethoxazole. Stillbirths, spontaneous abortions, and multiple gestations were excluded from the primary analysis. Potential risk factors for preterm birth (<37 weeks gestation) were evaluated by univariate and multivariate logistic regression. Results 356 women were included in this analysis. At enrollment, median gestational age was 21 weeks, median CD4 cell count was 368 cells/mm3. 14.7% of deliveries in the efavirenz arm and 16.2% in the lopinavir/ritonavir arm were preterm. Preterm birth was associated with gestational weight gain below 0.1 kg/week versus 0.1 kg/week or more (OR = 2.49, 95% CI: 1.38–4.47, p = 0.003). Neither ART regimen of lopinavir/ritonavir versus efavirenz (OR = 1.12, 95% CI: 0.63–2.00, p = 0.69) nor placental malaria (OR = 0.74, 95% CI: 0.38–1.44, p = 0.37) was associated with preterm birth. Conclusions Lopinavir/ritonavir was not associated with an increased risk of preterm birth compared to efavirenz. However, interventions are needed to address modifiable risk factors for preterm birth, such as nutritional status. (ClinicalTrials.gov, NCT00993031.)

Geophagy, the deliberate consumption of earth, is strongly associated with iron (Fe) deficiency. It has been proposed that geophagy may be practiced as a means to improve Fe status by increasing Fe intakes and, conversely, that geophagy may cause Fe deficiency by inhibiting Fe absorption. We tested these hypotheses by measuring Fe concentration and relative bioavailable Fe content of 12 samples of geophagic earth and 4 samples of pure clay minerals. Further, we assessed the impact of these samples on the bioavailability of Fe from an Fe-rich test meal (cooked white beans, WB). Fe concentrations were measured with inductively coupled plasma atomic emission spectroscopy. Fe bioavailability was determined using an in vitro digestion/Caco-2 cell model in which ferritin formation was used as an index of Fe bioavailability. Geophagic earth and clay mineral samples were evaluated with this model, both alone and in combination with WB (1:16 ratio, sample:WB). Median Fe concentration of the geophagic earth was 3485 (IQR 2462, 14571) μg/g and mean Fe concentration in the clay minerals was 2791 (± 1782) μg/g. All specimens had Fe concentrations significantly higher (p ≤ 0.005) than the Fe concentration of WB (77 μg/g). Ferritin formation (i.e. Fe uptake) in cells exposed to geophagic earths and clay minerals was significantly lower than in cells exposed to WB (p ≤ 0.05) and Fe uptake responses of 11 of the 16 samples were not significantly different from the blank, indicating no bioavailable Fe. When samples were combined with WB, 5 of 16 had mean ferritin levels that were significantly lower (p ≤ 0.05, one tail) than the WB alone, indicating that the samples inhibited Fe uptake from the WB. None of the ferritin responses of cells exposed to both WB and earth/clay were significantly higher than WB alone. Thus, although geophagic earths and mineral clays are high in total Fe, very little of this Fe is bioavailable. Further, some geophagic earth and clay mineral samples inhibit Fe absorption from foods. In vivo research is warranted to confirm these observations and to determine if geophagic earth samples can be a source of Fe and/or inhibit Fe absorption.

We evaluated the acceptability and use of macronutrient supplementation among HIV-infected pregnant Ugandan women receiving antiretroviral therapy in a clinical study (NCT 00993031). We first conducted formative research among 56 pregnant and lactating women to select a supplement regimen. Acceptability and use of the supplementation regimen [35 sachets of lipid-based nutrient supplements (LNS) and 4 or 6 kg of instant soy porridge for the household provided monthly] were evaluated among 87 pregnant women. Organoleptic assessments of LNS were favorable. Participants reported consuming LNS a mean of 6.1 days per week, and adherence to recommended consumption behaviors (e.g. frequency, quantity, not sharing) was >80%. Few women reported negative social consequences of supplementation. The majority of participants also consumed most of the porridge intended for the household. In sum, LNS was acceptable and used regularly. Larger studies to evaluate physical and psychosocial consequences of LNS during pregnancy among HIV-infected women are warranted.

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Ugandan guidelines recommend 6 months of exclusive breastfeeding (EBF) for HIV‐infected women on antiretroviral therapy (ART), with continued breastfeeding (BF) for at least 1 year. We explored infant feeding (IF) practices and beliefs among HIV‐infected pregnant and BF women on ART in the PROMOTE trial (NCT00993031) in Tororo, Uganda. IF practices were determined using monthly maternal reports from a prospective cohort of 219 PROMOTE infants born between March 6, 2010 and October 31, 2011 and compared to 2007 Ugandan Demographic and Health Survey (DHS) data. To assess IF beliefs, a purposive sample of 24 pregnant and 32 BF PROMOTE participants took part in in‐depth interviews (IDIs) in July and August 2011 (n=56). In the PROMOTE study, the prevalence of EBF was 90.4% and 71.6% at 3 and 6 months, vs. 64.8% and 10.8% respectively in the DHS. In contrast, the prevalence of BF at 12 months was 62.6% in PROMOTE vs. 88.3% in DHS. IDIs revealed several potential reasons for suboptimal IF: 64.3% believed that HIV was an important reason to avoid BF and 21.4% did not know the recommended duration of EBF. Of BF IDI participants, 78.1% were concerned about adequate breast milk production and 46.9% had actually experienced problems with EBF, e.g. unsatisfied baby. Among all IDI participants, 96.4% desired further IF education. Further research is needed to understand optimal support to overcome identified obstacles to BF among HIV+ women in rural Uganda.Grant Funding Source: National Institute of Child Health and Human Development