Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 45 Records) |
Query Trace: Chasela C[original query] |
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Determining the lower limit of detection required for HCV viral load assay for test of cure following direct-acting antiviral-based treatment regimens: Evidence from a global data set.
Morgan JR , Marsh E , Savinkina A , Shilton S , Shadaker S , Tsertsvadze T , Kamkamidze G , Alkhazashvili M , Morgan T , Belperio P , Backus L , Doss W , Esmat G , Hassany M , Elsharkawy A , Elakel W , Mehrez M , Foster GR , Wose K , Chew KW , Chasela CS , Sanne IM , Thanung YM , Loarec A , Aslam K , Balkan S , Easterbrook PJ , Linas BP . J Viral Hepat 2022 29 (6) 474-486 Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12-weeks post-treatment (SVR12). We assembled a global dataset of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique), and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90(th) , 95th, 97th, and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5,973 cases of detectable viremia at SVR12 from the combined dataset. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95(th) percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viremia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR=1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure. |
Developing excellence in biostatistics leadership, training and science in Africa: How the Sub-Saharan Africa Consortium for Advanced Biostatistics (SSACAB) trainingunites expertise to deliver excellence
Chirwa TF , Matsena Zingoni Z , Munyewende P , Manda SO , Mwambi H , Kandala NB , Kinyanjui S , Young T , Musenge E , Simbeye J , Musonda P , Mahande MJ , Weke P , Onyango NO , Kazembe L , Tumwesigye NM , Zuma K , Yende-Zuma N , Omanyondo Ohambe MC , Kweku EN , Maposa I , Ayele B , Achia T , Machekano R , Thabane L , Levin J , Eijkemans MJC , Carpenter J , Chasela C , Klipstein-Grobusch K , Todd J . AAS Open Res 2020 3 51 The increase in health research in sub-Saharan Africa (SSA) has led to a high demand for biostatisticians to develop study designs, contribute and apply statistical methods in data analyses. Initiatives exist to address the dearth in statistical capacity and lack of local biostatisticians in SSA health projects. The Sub-Saharan African Consortium for Advanced Biostatistics (SSACAB) led by African institutions was initiated to improve biostatistical capacity according to the needs identified by African institutions, through collaborative masters and doctoral training in biostatistics. SACCAB has created a critical mass of biostatisticians and a network of institutions over the last five years and has strengthened biostatistics resources and capacity for health research studies in SSA. SSACAB comprises 11 universities and four research institutions which are supported by four European universities. In 2015, only four universities had established Masters programmes in biostatistics and SSACAB supported the remaining seven to develop Masters programmes. In 2019 the University of the Witwatersrand became the first African institution to gain Royal Statistical Society accreditation for a Biostatistics Masters programme. A total of 150 fellows have been awarded scholarships to date of which 123 are Masters fellowships (41 female) of whom 58 have already graduated. Graduates have been employed in African academic (19) and research (15) institutions and 10 have enrolled for PhD studies. A total of 27 (10 female) PhD fellowships have been awarded; 4 of them are due to graduate by 2020. To date, SSACAB Masters and PhD students have published 17 and 31 peer-reviewed articles, respectively. SSACAB has also facilitated well-attended conferences, face-to-face and online short courses. Pooling of limited biostatistics resources in SSA combined with co-funding from external partners has shown to be an effective strategy for the development and teaching of advanced biostatistics methods, supervision and mentoring of PhD candidates. |
Antiretroviral drug concentrations in breastmilk, maternal HIV viral load, and HIV transmission to the infant: results from the BAN study
Davis NL , Corbett A , Kaullen J , Nelson JAE , Chasela CS , Sichali D , Hudgens MG , Miller WC , Jamieson DJ , Kourtis AP . J Acquir Immune Defic Syndr 2018 80 (4) 467-473 BACKGROUND: Concentration of antiretroviral (ARV) drug found in plasma, and amounts of drug excreted into breastmilk, may affect HIV viral load and potentially perinatal HIV transmission. METHODS: In this cohort study with two-phase sampling, we included mothers randomized to postpartum maternal ARVs or daily infant nevirapine during 28 weeks of breastfeeding in the Breastfeeding, Antiretrovirals and Nutrition (BAN) study. Among these, we included all mothers who transmitted HIV to their infants between 2-28 weeks and 15% of mothers who did not (n=27 and 227, respectively). Spearman correlation coefficients (r2) were used to assess correlation between maternal plasma and breastmilk ARV concentration. Associations between the median effective drug concentration (EC50) and detectable maternal viral load (plasma: >40 copies/ml, breastmilk: >56 copies/ml) were assessed using mixed effects models. Cox models were used to estimate the association between maternal or infant plasma drug concentration and breastmilk HIV transmission from 2-28 weeks. RESULTS: All ARV compounds exhibited substantial correlations between maternal plasma and breastmilk concentrations (r2: 0.85-0.98, p-value <0.0001). Having plasma drug concentration above the EC50 was associated with lower odds of having detectable HIV RNA (maternal plasma OR 0.64, 95%CI 0.45-0.91; breastmilk OR 0.22, 95% CI 0.14-0.35) and a reduced rate of breastmilk HIV transmission (HR 0.40, 95% CI 0.18-0.93). Having breastmilk drug concentration above the EC50 was also associated with lower odds of having detectable maternal HIV RNA (plasma OR 0.62, 95%CI 0.45-0.85; breastmilk OR 0.42, 95% CI 0.29-0.59). CONCLUSION: Ensuring adequate drug concentration is important for viral suppression and preventing breastmilk HIV transmission. |
Predictors of perinatal HIV transmission among women without prior antiretroviral therapy in a resource-limited setting: The BAN Study
Ewing AC , Ellington SR , Wiener JB , Chasela CS , Tegha G , Nelson JAE , Jamieson DJ , van der Horst C , Kourtis AP . Pediatr Infect Dis J 2018 38 (5) 508-512 OBJECTIVES: To investigate potential risk factors for perinatal (intrauterine and intrapartum) mother-to-child transmission of HIV (MTCT) in women unexposed to Antiretroviral Therapy (ART) during pregnancy. METHODS: We compared factors according to perinatal MTCT outcome among 2,275 ART-naive (until the onset of labor) HIV-infected women in the Breastfeeding, Antiretrovirals and Nutrition study (2004-2010) in Lilongwe, Malawi. Factors included HIV viral load during pregnancy, food security, demographic characteristics, hematologic and blood chemistry measures, medical history and physical factors. Associations with perinatal MTCT and interactions with maternal viral load were assessed using simple and multivariable logistic regression. RESULTS: There were 119 (115 intrauterine, 4 intrapartum) cases of perinatal MTCT; only one to a mother with <1,000 HIV copies/mL. Maternal viral loads >10,000 copies/mL were common (63.1%). Lower maternal viral load (<1,000 copies/mL and 1,000.1-10,000 copies/mL) was associated with reduced odds of perinatal MTCT [adjusted odds ratio (aOR), 0.1; 95% confidence interval (CI), 0.01-0.4 and aOR, 0.2; 95% CI, 0.1-0.4, respectively), compared with maternal viral load >10,000 copies/mL. Low CD4+ T cell count (</= 350 cells/microL) was only associated with perinatal MTCT in unadjusted models. Food shortage (aOR, 1.8; 95% CI; 1.2-2.6), sexually transmitted infection (past year) (aOR, 1.9; 95% CI; 1.0-3.7), histories of herpes zoster (aOR, 3.0; 95% CI; 1.6-5.6) and tuberculosis (aOR, 2.5; 95% CI; 1.1-5.7) were associated with increased odds of perinatal MTCT. CONCLUSIONS: These findings confirm that lowering maternal HIV viral load is most important in preventing perinatal MTCT, and support efforts to address food shortage, STD and TB prevention, while informing programs to improve ART coverage in pregnancy. |
Maternal but not infant anti-HIV-1 neutralizing antibody response associates with enhanced transmission and infant morbidity
Ghulam-Smith M , Olson A , White LF , Chasela CS , Ellington SR , Kourtis AP , Jamieson DJ , Tegha G , van der Horst CM , Sagar M . mBio 2017 8 (5) A significant number of infants acquire HIV-1 through their infected mother's breast milk, primarily due to limited access to antiretrovirals. Passive immunization with neutralizing antibodies (nAbs) may prevent this transmission. Previous studies, however, have generated conflicting results about the ability of nAbs to halt mother-to-child transmission (MTCT) and their impact on infant outcomes. This study compared plasma neutralizing activity in exposed infants and the infected mothers (n = 63) against heterologous HIV-1 variants and the quasispecies present in the mother. HIV-exposed uninfected infants (HEU) (n = 42), compared to those that eventually acquired infection (n = 21), did not possess higher nAb responses against heterologous envelopes (P = 0.46) or their mothers' variants (P = 0.45). Transmitting compared to nontransmitting mothers, however, had significantly higher plasma neutralizing activity against heterologous envelopes (P = 0.03), although these two groups did not have significant differences in their ability to neutralize autologous strains (P = 0.39). Furthermore, infants born to mothers with greater neutralizing breadth and potency were significantly more likely to have a serious adverse event (P = 0.03). These results imply that preexisting anti-HIV-1 neutralizing activity does not prevent breast milk transmission. Additionally, high maternal neutralizing breadth and potency may adversely influence both the frequency of breast milk transmission and subsequent infant morbidity.IMPORTANCE Passive immunization trials are under way to understand if preexisting antibodies can decrease mother-to-child HIV-1 transmission and improve infant outcomes. We examined the influence of preexisting maternal and infant neutralizing activity on transmission and infant morbidity in a breastfeeding mother-infant cohort. Neutralization was examined against both the exposure strains circulating in the infected mothers and a standardized reference panel previously used to estimate breadth. HIV-exposed uninfected infants did not possess a broader and more potent response against both the exposure and heterologous strains compared to infants that acquired infection. Transmitting, compared to nontransmitting, mothers had significantly higher neutralization breadth and potency but similar responses against autologous variants. Infants born to mothers with higher neutralization responses were more likely to have a serious adverse event. Our results suggest that preexisting antibodies do not protect against breast milk HIV-1 acquisition and may have negative consequences for the baby. |
Effects of concurrent exposure to antiretrovirals and cotrimoxazole prophylaxis among HIV-exposed, uninfected infants
Ewing AC , King CC , Wiener JB , Chasela CS , Hudgens MG , Kamwendo D , Tegha G , Hosseinipour MC , Jamieson DJ , Van der Horst C , Kourtis AP . AIDS 2017 31 (18) 2455-2463 BACKGROUND: Given the potential of cotrimoxazole preventive therapy (CPT) to prevent bacterial and malarial infections in HIV-exposed, uninfected (HEU) infants, it is important to evaluate the effects of its concurrent use with antiretroviral agents that have overlapping toxicity profiles. METHODS: We used data from the Breastfeeding, Antiretrovirals, and Nutrition study (2004-2010) to evaluate the association of CPT and antiretrovirals with hematologic measures (hemoglobin, neutrophil, and alanine aminotransferase levels) from 6 to 48 weeks of age in 2006 HEU infants in Lilongwe, Malawi. Hazards of severe outcomes (anemia, neutropenia, and elevated alanine aminotransferase), as defined by the National Institutes of Health, were compared using Cox regression models, according to time-varying CPT (implemented June 2006), antiretroviral treatment arm (maternal triple antiretroviral, infant nevirapine, or none during 6 months of breastfeeding), and their interaction. The effects of these treatments on hemoglobin, neutrophil, and alanine aminotransferase levels were assessed using linear mixed models. RESULTS: In Cox models, CPT was associated with an increase in severe neutropenia [hazard ratio 1.97 (1.01, 3.86)] and a decrease in severe anemia (hazard ratio 0.65 (0.48, 0.88)]. Interactions between CPT and antiretroviral treatment were not significant. By 36 weeks, there was a significant association of CPT with increased hemoglobin levels regardless of antiretroviral drug exposure. CONCLUSIONS: In addition to expected associations with increased hazard of severe neutropenia and decreased neutrophil count, CPT was associated with reduced hazard of severe anemia and higher infant blood hemoglobin. This provides further support for CPT use in HEU infants in malaria-endemic resource-limited settings where anemia is prevalent. |
The effects of a lipid-based nutrient supplement and antiretroviral therapy in a randomized controlled trial on iron, copper, and zinc in milk from HIV-infected Malawian mothers and associations with maternal and infant biomarkers
Hampel D , Shahab-Ferdows S , Gertz E , Flax VL , Adair LS , Bentley ME , Jamieson DJ , Tegha G , Chasela CS , Kamwendo D , van der Horst CM , Allen LH . Matern Child Nutr 2017 14 (2) e12503 We evaluated effects of antiretroviral (ARV) therapy and lipid-based nutrient supplements (LNSs) on iron, copper, and zinc in milk of exclusively breastfeeding HIV-infected Malawian mothers and their correlations with maternal and infant biomarkers. Human milk and blood at 2, 6, and 24 weeks post-partum and blood during pregnancy (≤30 weeks gestation) were collected from 535 mothers/infant-pairs in the Breastfeeding, Antiretrovirals, and Nutrition study. The participants received ARV, LNS, ARV and LNS, or no intervention from 0 to 28 weeks post-partum. ARVs negatively affected copper and zinc milk concentrations, but only at 2 weeks, whereas LNS had no effect. Among all treatment groups, approximately 80-90% of copper and zinc and <50% of iron concentrations met the current adequate intake for infants at 2 weeks and only 1-19% at 24 weeks. Pregnancy haemoglobin was negatively correlated with milk iron at 2 and 6 weeks (r = -.18, p < .02 for both). The associations of the milk minerals with each other were the strongest correlations observed (r = .11-.47, p < .05 for all); none were found with infant biomarkers. At 2 weeks, moderately anaemic women produced milk higher in iron when ferritin was higher or TfR lower. At 6 weeks, higher maternal alpha-1-acid glycoprotein and C-reactive protein were associated with higher milk minerals in mildly anaemic women. Infant TfR was lower when milk mineral concentrations were higher at 6 weeks and when mothers were moderately anaemic during pregnancy. ARV affects copper and zinc milk concentrations in early lactation, and maternal haemoglobin during pregnancy and lactation could influence the association between milk minerals and maternal and infant iron status and biomarkers of inflammation. |
Maternal humoral immune correlates of peripartum transmission of Clade C HIV-1 in the setting of peripartum antiretrovirals
Mutucumarana CP , Eudailey J , McGuire EP , Vandergrift N , Tegha G , Chasela C , Ellington S , van der Horst C , Kourtis AP , Permar SR , Fouda GG . Clin Vaccine Immunol 2017 24 (8) Despite widespread use of antiretrovirals (ARV), more than 150,000 pediatric HIV-1 infections continue to occur annually. Supplemental strategies are necessary to eliminate pediatric HIV infections. We previously reported that maternal HIV envelope-specific anti-V3 IgG, CD4 binding site-directed antibodies, and tier 1 virus neutralization predicted reduced risk of mother-to-child transmission of HIV-1 (MTCT) in the pre-ARV era US-based Women and Infants Transmission Study (WITS) cohort. As the majority of ongoing pediatric HIV infections occur in sub-Saharan Africa, we sought to determine if the same maternal humoral immune correlates predicted MTCT in a subset of the Malawian Breastfeeding, Antiretrovirals, and Nutrition (BAN) cohort of HIV-infected mothers (n=88, 45 transmitting and 43 non-transmitting). Women and infants received ARV at delivery, thus the majority of MTCT was in utero (91%). In a multivariable logistic regression model, neither maternal anti-V3 IgG nor clade C tier 1 virus neutralization were associated with MTCT. Unexpectedly, maternal CD4 binding site antibodies and anti-V1V2 IgG were associated with increased MTCT, independent of maternal viral load. Neither infant Env-specific IgG levels nor maternal IgG transplacental transfer efficiency were associated with transmission. Distinct humoral immune correlates of MTCT in the BAN and WITS studies could be due to differences between transmission mode, virus clade, or maternal antiretroviral use. The association between specific maternal antibody responses and in utero transmission, distinct from potentially protective maternal antibodies in the WITS cohort, underlines the importance of investigating additional cohorts with well-defined transmission modes to understand the role of antibodies during HIV-1 MTCT. |
Co-trimoxazole prophylaxis, asymptomatic malaria parasitemia, and infectious morbidity in HIV-exposed uninfected infants in Malawi: The BAN study
Davis NL , Wiener J , Juliano JJ , Adair L , Chasela CS , Kayira D , Hudgens MG , van der Horst C , Jamieson DJ , Kourtis AP . Clin Infect Dis 2017 65 (4) 575-580 Background: HIV-exposed infants are disproportionately at risk of morbidity and mortality compared with their HIV-unexposed counterparts. The role of co-trimoxazole preventive therapy (CPT) in reducing leading causes of infectious morbidity is unclear. Methods: We used data from the Breastfeeding, Antiretrovirals and Nutrition (BAN) clinical trial (conducted 2004-2010, Malawi) to assess the association of 1) CPT and 2) asymptomatic malaria parasitemia with respiratory and diarrheal morbidity in infants. In June 2006, all HIV-exposed infants in BAN began receiving CPT (240 mg) from 6-36 weeks of age, or until weaning occurred and HIV infection was ruled out. All HIV-exposed, uninfected infants (HEI) at 8 weeks of age (n=1984) were included when CPT was the exposure. A subset of HEI (n=471) were tested for malarial parasitemia using dried blood spots from 12, 24, and 36 weeks of age. Cox proportional hazards models for recurrent gap-time data were used to examine the association of time-varying exposures on morbidity. Results: CPT was associated with a 36% reduction in respiratory morbidity (hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.60-0.69) and a 41% reduction in diarrheal morbidity (HR 0.59, 95% CI 0.54-0.65). Having asymptomatic malaria parasitemia was associated with a 40% increase in respiratory morbidity (HR 1.40, 95% CI 1.13-1.74) and a 50% increase in diarrheal morbidity (HR 1.50, 95% CI 1.09-2.06), after adjusting for CPT. Conclusion: CPT may have an important role to play in reducing the leading global causes of morbidity and mortality in the growing population of HEIs in malaria-endemic resource-limited settings. |
Maternal and neonatal outcomes among women with HIV infection and their infants in Malawi
Chevalier MS , King CC , Ellington S , Wiener J , Kayira D , Chasela CS , Jamieson DJ , Kourtis AP . Int J Gynaecol Obstet 2017 137 (3) 282-289 OBJECTIVE: To describe maternal and neonatal morbidity and mortality among women with HIV infection and their infants. METHODS: A secondary analysis was undertaken of data obtained in the BAN Study, a trial of postnatal antiretrovirals among pregnant women with HIV infection enrolled in 2004-2010. Mothers and infants had 13 scheduled visits through 48 weeks of follow-up. Serious maternal morbidity and mortality were examined at delivery (n=2791), from delivery to 6 weeks later (n=2369) and from 7 to 48 weeks (n=1980). Neonatal morbidity and mortality were examined (n=2685). RESULTS: Of 2791 deliveries, 169 (6.1%) were by cesarean (153 emergency). Compared with women with vaginal delivery, those with cesarean delivery had lower prenatal HIV viral loads (P=0.016) and increased odds of pre-eclampsia/eclampsia (odds ratio [OR] 10.8, 95% CI 4.4-26.8). Women with cesarean delivery also had increased odds of serious infection with 14 days of delivery (OR 3.0, 95% CI 1.3-7.4) and severe anemia (grade 3 or 4) by 6 weeks (OR 6.7, 95% CI 2.3-19.1). Infants born by cesarean had increased odds of a low 5-minute Apgar score (OR 8.1, 95% CI 3.5-18.6) and admission to an intensive care unit (OR 5.4, 95% CI 3.7-7.8). CONCLUSION: Odds of serious maternal and neonatal morbidity were higher after cesarean than vaginal delivery, despite lower maternal viral loads. This article is protected by copyright. All rights reserved. |
Effect of postnatal HIV treatment on clinical mastitis and breast inflammation in HIV-infected breast-feeding women
Zadrozny S , Westreich D , Hudgens MG , Chasela C , Jamieson DJ , Martinson F , Zimba C , Tegha G , Hoffman I , Miller WC , Pence BW , King CC , Kourtis AP , Msungama W , van der Horst C . Paediatr Perinat Epidemiol 2017 31 (2) 134-143 BACKGROUND: The relationship between mastitis and antiretroviral therapy among HIV-positive, breast-feeding women is unclear. METHODS: In the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study, conducted in Lilongwe, Malawi, 2369 mother-infant pairs were randomized to a nutritional supplement group and to one of three treatment groups: maternal antiretroviral therapy (ART), infant nevirapine (NVP) or standard of care for 24 weeks of exclusive breast-feeding and 4 weeks of weaning. Among 1472 HIV-infected women who delivered live infants between 2004 and 2007, we estimated cumulative incidence functions and sub-distribution hazard ratios (HR) of mastitis or breast inflammation comparing women in maternal ART (n = 487) or infant nevirapine (n = 492) groups to the standard of care (n = 493). Nutritional supplement groups (743 took, 729 did not) were also compared. RESULTS: Through 28-weeks post-partum, 102 of 1472 women experienced at least one occurrence of mastitis or breast inflammation. The 28-week risk was higher for maternal ART (risk difference (RD) 4.5, 95% confidence interval (CI) 0.9, 8.1) and infant NVP (RD 3.6, 95% CI 0.3, 6.9) compared to standard of care. The hazard of late-appearing mastitis or breast inflammation (from week 5-28) was also higher for maternal ART (HR 6.7, 95% CI 2.0, 22.6) and infant NVP (HR 5.1, 95% CI 1.5, 17. 5) compared to the standard of care. CONCLUSIONS: Mastitis or breast inflammation while breast-feeding is a possible side effect for women taking prophylactic ART and women whose infants take NVP, warranting additional research in the context of postnatal HIV transmission. |
Maternal and Breastmilk Viral Load: Impacts of Adherence on Peripartum HIV Infections Averted-The Breastfeeding, Antiretrovirals, and Nutrition Study.
Davis NL , Miller WC , Hudgens MG , Chasela CS , Sichali D , Kayira D , Nelson JA , Fiscus SA , Tegha G , Kamwendo DD , Rigdon J , Stringer JS , Juliano JJ , Ellington SR , Kourtis AP , Jamieson DJ , Van Der Horst C . J Acquir Immune Defic Syndr 2016 73 (5) 572-580 BACKGROUND: Antiretroviral interventions are used to reduce HIV viral replication and prevent mother-to-child transmission. Viral suppression relies on adherence to antiretrovirals. METHODS: A two-phase study was conducted using data from the Breastfeeding, Antiretrovirals and Nutrition study. We included mothers randomized to 28 weeks of postpartum antiretrovirals with ≥1 plasma or breastmilk specimen. All mothers who transmitted HIV to their infants from 2-28 weeks (n=31) and 15% of mothers who did not (n=232) were included. Adherence was measured by pill count [categorized as poor (0-80%), partial (81-98%) and near perfect (>98%)]. Associations between adherence and breastmilk RNA were assessed using mixed effects models. Cox models were used to estimate associations between breastmilk RNA and HIV transmission. Using Monte Carlo simulation, we estimated the number of transmissions that would occur had everyone randomized to maternal ARVs been 90% and 100% adherent. RESULTS: Partial or near perfect antiretroviral adherence significantly reduced the odds of having detectable (≥40 copies/ml) breastmilk RNA, compared to poor adherence (OR 0.23, 95% CI 0.08-0.67; OR 0.36, 95% CI 0.16-0.81, respectively). Detectable breastmilk RNA was associated with increased breastmilk transmission, compared to undetectable breastmilk RNA (HR 3.8, 95% CI 1.2-12.1). All transmitting mothers had ≥1 plasma viral load specimen >100 copies/ml. An estimated similar number of transmissions would occur with 90% adherence compared with 100%. CONCLUSIONS: Helping patients adhere to antiretrovirals throughout breastfeeding is important for realizing the full potential of recommended antiretroviral interventions to prevent mother-to-child HIV transmission. Maintaining plasma viral load <100 copies/ml may prevent breastmilk transmission. |
Role of antibiotics in reducing childhood mortality in resource-poor settings
Kourtis AP , Jamieson DJ , Chasela C , van der Horst C . AIDS 2016 30 (8) 1310-1 A recent article ‘A quiet revolution in the treatment of childhood diarrhea’ in the New York Times[1] highlights childhood diarrhea, a ‘silent’ killer of infants and children in resource-poor settings, second in magnitude only to pneumonia. Diarrhea treatment guidelines in such settings rely on oral rehydration and reserve antibiotics for the presence of blood in the stool. These guidelines were developed more than 30 years ago. Newer evidence points to the higher than previously thought frequency of bacterial causes, even in the absence of visible blood in the stool [1]. Some experts argue that empiric antibiotic treatment of childhood diarrhea in resource-poor settings is a more cost-effective option than microbiologic testing to determine the cause. Others argue that such use of antibiotics will lead to widespread resistance. | Several lines of recent evidence have shown a benefit of administering antibiotics to children in resource-poor settings in which malaria is also prevalent. Use of daily cotrimoxazole prophylaxis in HIV-exposed, uninfected infants in Malawi significantly reduced the risk of infant pneumonia, diarrhea, and malaria, and halved the risk of infant death [2]. Another study in Malawi compared the combination of chloroquine with azithromycin to chloroquine alone as treatment for symptomatic malaria episodes in children [3]; the combination with azithromycin not only treated malaria, but also decreased the incidence of subsequent respiratory infections by 33% and gastrointestinal tract infections by 26%. These data complement those of yet another study in Malawi, which demonstrated a 40% reduction in mortality in children by adding amoxicillin or cefdinir to ready-to-use food for the outpatient treatment of acute severe malnutrition [4], and those of a study of mass treatment for trachoma with azithromycin in Ethiopia [5], which demonstrated a decrease in childhood mortality. |
Thiamin and riboflavin in human milk: Effects of lipid-based nutrient supplementation and stage of lactation on vitamer secretion and contributions to total vitamin content
Hampel D , Shahab-Ferdows S , Adair LS , Bentley ME , Flax VL , Jamieson DJ , Ellington SR , Tegha G , Chasela CS , Kamwendo D , Allen LH . PLoS One 2016 11 (2) e0149479 While thiamin and riboflavin in breast milk have been analyzed for over 50 years, less attention has been given to the different forms of each vitamin. Thiamin-monophosphate (TMP) and free thiamin contribute to total thiamin content; flavin adenine-dinucleotide (FAD) and free riboflavin are the main contributors to total riboflavin. We analyzed milk collected at 2 (n = 258) or 6 (n = 104), and 24 weeks (n = 362) from HIV-infected Malawian mothers within the Breastfeeding, Antiretrovirals and Nutrition (BAN) study, randomly assigned at delivery to lipid-based nutrient supplements (LNS) or a control group, to investigate each vitamer's contribution to total milk vitamin content and the effects of supplementation on the different thiamin and riboflavin vitamers at early and later stages of lactation, and obtain insight into the transport and distribution of these vitamers in human milk. Thiamin vitamers were derivatized into thiochrome-esters and analyzed by high-performance liquid-chromatography-fluorescence-detection (HPLC-FLD). Riboflavin and FAD were analyzed by ultra-performance liquid-chromatography-tandem-mass-spectrometry (ULPC-MS/MS). Thiamin-pyrophosphate (TPP), identified here for the first time in breast milk, contributed 1.9-4.5% to total thiamin. Free thiamin increased significantly from 2/6 to 24 weeks regardless of treatment indicating an active transport of this vitamer in milk. LNS significantly increased TMP and free thiamin only at 2 weeks compared to the control: median 170 versus 151mug/L (TMP), 13.3 versus 10.5mug/L (free thiamin, p<0.05 for both, suggesting an up-regulated active mechanism for TMP and free thiamin accumulation at early stages of lactation. Free riboflavin was consistently and significantly increased with LNS (range: 14.8-19.6mug/L (LNS) versus 5.0-7.4mug/L (control), p<0.001), shifting FAD:riboflavin relative amounts from 92-94:6-8% to 85:15%, indicating a preferred secretion of the free form into breast milk. The continuous presence of FAD in breast milk suggests an active transport and secretion system for this vitamer or possibly formation of this co-enymatic form in the mammary gland. |
Antiretroviral therapy provided to HIV-infected Malawian women in a randomized trial diminishes the positive effects of lipid-based nutrient supplements on breast-milk B vitamins
Allen LH , Hampel D , Shahab-Ferdows S , York ER , Adair LS , Flax VL , Tegha G , Chasela CS , Kamwendo D , Jamieson DJ , Bentley ME . Am J Clin Nutr 2015 102 (6) 1468-74 BACKGROUND: Little information is available on B vitamin concentrations in human milk or on how they are affected by maternal B vitamin deficiencies, antiretroviral therapy, or maternal supplementation. OBJECTIVE: The objective was to evaluate the effects of antiretroviral therapy and/or lipid-based nutrient supplements (LNSs) on B vitamin concentrations in breast milk from HIV-infected women in Malawi. DESIGN: Breast milk was collected from 537 women recruited within the Breastfeeding, Antiretrovirals, and Nutrition study at 2 or 6 wk and 24 wk postpartum. Women were assigned to receive antiretrovirals and LNSs, antiretrovirals only, LNSs only, or a control. Antiretrovirals and LNSs were given to the mothers from weeks 0 to 28. The antiretrovirals were zidovudine/lamivudine and nelfinavir or lopinavir/ritonavir. LNSs provided 93-118% of the Recommended Dietary Allowances of thiamin, riboflavin, niacin, pyridoxine, and vitamin B-12. Infants were exclusively breastfed. RESULTS: LNSs increased milk concentrations of all vitamins except thiamin, whereas antiretrovirals lowered concentrations of nicotinamide, pyridoxal, and vitamin B-12. Although antiretrovirals alone had no significant effect on riboflavin concentrations, they negatively affected the LNS-induced increase in this vitamin. Thiamin was not influenced by the study interventions. Concentrations of all B vitamins were much lower than usually accepted values. CONCLUSIONS: All B vitamins were low in milk, and all but thiamin were increased by maternal supplementation with LNSs. Antiretrovirals alone decreased concentrations of some B vitamins in milk. When LNS was given in addition to antiretrovirals, the negative effect of antiretrovirals offset the positive effect of LNSs for all vitamins except thiamin. This trial was registered at clinicaltrials.gov as NCT00164762. |
Plasma micronutrient concentrations are altered by antiretroviral therapy and lipid-based nutrient supplements in lactating HIV-infected Malawian women
Flax VL , Adair LS , Allen LH , Shahab-Ferdows S , Hampel D , Chasela CS , Tegha G , Daza EJ , Corbett A , Davis NL , Kamwendo D , Kourtis AP , van der Horst CM , Jamieson DJ , Bentley ME . J Nutr 2015 145 (8) 1950-7 BACKGROUND: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient concentrations of HIV-infected lactating women in resource-constrained settings. OBJECTIVE: We examined associations of highly active antiretroviral therapy (HAART) and lipid-based nutrient supplements (LNS) with concentrations of selected micronutrients in HIV-infected Malawian women at 24 wk postpartum. METHODS: Plasma micronutrient concentrations were measured in a subsample (n = 690) of Breastfeeding, Antiretrovirals, and Nutrition (BAN) study participants who were randomly assigned at delivery to receive HAART, LNS, HAART+LNS, or no HAART/no LNS (control). HAART consisted of protease inhibitor-based triple therapy. LNS (140 g/d) met energy and micronutrient requirements of lactation. Multivariable linear regression tested the association of HAART and LNS, plus their interaction, with micronutrient concentrations, controlling for season, baseline viral load, and baseline CD4 count. RESULTS: We found significant HAART by LNS interactions for folate (P = 0.051), vitamin B-12 (P < 0.001), and transferrin receptors (TfRs) (P = 0.085). HAART was associated with lower folate (with LNS: -27%, P < 0.001; without LNS: -12%, P = 0.040) and higher TfR concentrations (with LNS: +14%, P = 0.004; without LNS: +28%, P < 0.001), indicating iron deficiency. LNS increased folate (with HAART: +17%, P = 0.037; without HAART: +39%, P < 0.001) and decreased TfR concentrations (with HAART only: -12%, P = 0.023). HAART was associated with lower vitamin B-12 concentrations only when LNS was present (-18%, P = 0.001), whereas LNS increased vitamin B-12 only when no HAART was present (+27%, P < 0.001). HAART, but not LNS, was associated with higher retinol-binding protein (RBP; +10%, P = 0.007). We detected no association of HAART or LNS with selenium, ferritin, or hemoglobin. CONCLUSION: The association of HAART with lower folate, iron deficiency, and higher RBP plus the attenuation of LNS effects on folate and vitamin B-12 when combined with HAART has implications for the health of lactating HIV-infected women taking HAART in prevention of mother-to-child transmission programs. This trial was registered at clinicaltrials.gov as NCT00164736. |
Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding
King CC , Kourtis AP , Persaud D , Nelson JA , Ziemniak C , Hudgens MG , Tegha G , Chasela CS , Jamieson DJ , van der Horst CM . AIDS 2015 29 (15) 1953-61 OBJECTIVE: The objective of this study is to determine whether detection of HIV infection was delayed in infants exposed to antiretroviral prophylaxis to prevent HIV transmission during breastfeeding. DESIGN: The Breastfeeding, Antiretrovirals and Nutrition (BAN) study was a randomized trial of 2369 mother-infant pairs conducted from 2004 to 2010. In addition to an intrapartum regimen, all mother-infant pairs were randomly assigned to three antiretroviral intervention arms during 28 weeks of breastfeeding: no further antiretroviral prophylaxis (control arm); infant-daily nevirapine (nevirapine arm); and maternal zidovudine, lamivudine and either nevirapine, nelfinavir or lopinavir-ritonavir (maternal arm). After breastfeeding cessation counselling and stopping the antiretroviral interventions by 28 weeks, 28 infant HIV infections occurred. METHODS: To determine whether these infections occurred during the breastfeeding and antiretroviral intervention phase but had delayed detection on the antiretroviral arms, we performed ultrasensitive (droplet digital PCR) HIV testing on infants with stored peripheral blood mononuclear cell (PBMC) specimens at 24 weeks (n = 9). RESULTS: Of the nine infants, all three on the infant nevirapine arm had detectable HIV DNA at 24 weeks, compared with two of four on the maternal antiretroviral arm and one of two on the control arm. For infants with detectable HIV at 24 weeks, the median delay in detection between the ultrasensitive and standard assays was 18.3 weeks for the nevirapine arm, 15.4 weeks for the maternal arm and 9.4 weeks for the control arm. CONCLUSION: The prolonged inability to detect HIV with standard assays in the context of postnatal antiretroviral prophylaxis suggests that early antiretrovirals may restrict HIV replication sufficiently to lead to missed diagnosis among infected infants. Therefore, repeat virologic testing is warranted beyond the WHO-recommended point of testing at 6 weeks after breastfeeding cessation. |
Effect of cytomegalovirus infection on breastfeeding transmission of HIV and on the health of infants born to HIV-infected mothers
Chang TS , Wiener J , Dollard SC , Amin MM , Ellington S , Chasela C , Kayira D , Tegha G , Kamwendo D , Jamieson DJ , Van Der Horst C , Kourtis AP . AIDS 2015 29 (7) 831-836 BACKGROUND: Cytomegalovirus (CMV) infection can be acquired in utero or postnatally through horizontal transmission and breastfeeding. The effect of postnatal CMV infection on postnatal HIV transmission is unknown. METHODS: The Breastfeeding, Antiretrovirals and Nutrition study, conducted in Malawi, randomized 2369 mothers and their infants to three antiretroviral prophylaxis arms - mother (triple regimen), infant (nevirapine), or neither - for 28 weeks of breastfeeding, followed by weaning. Stored plasma and peripheral blood mononuclear cell specimens were available for 492 infants at 24 weeks and were tested with CMV PCR. Available samples from infants who were CMV PCR-positive at 24 weeks were also tested at birth (N = 242), and from infants PCR-negative at 24 weeks were tested at 48 weeks (N = 96). Cox proportional-hazards models were used to determine if CMV infection was associated with infant morbidity, mortality, or postnatal HIV acquisition. RESULTS: At 24 weeks of age, CMV DNA was detected in 345/492 infants (70.1%); the estimated congenital CMV infection rate was 2.3%, and the estimated rate of CMV infection at 48 weeks was 78.5%. CMV infection at 24 weeks was associated with subsequent HIV acquisition through breastfeeding or infant death between 24 and 48 weeks of age (hazard ratio 4.27, P = 0.05). CONCLUSION: Most breastfed infants of HIV-infected mothers in this resource-limited setting are infected with CMV by 24 weeks of age. Early CMV infection may be a risk factor for subsequent infant HIV infection through breastfeeding, pointing to the need for comprehensive approaches in order to achieve elimination of breastfeeding transmission of HIV. |
Impact of daily cotrimoxazole on clinical malaria and asymptomatic parasitemias in HIV-exposed uninfected infants
Davis NL , Barnett EJ , Miller WC , Dow A , Chasela CS , Hudgens MG , Kayira D , Tegha G , Ellington SR , Kourtis AP , van der Horst C , Jamieson DJ , Juliano JJ . Clin Infect Dis 2015 61 (3) 368-74 BACKGROUND: Cotrimoxazole preventive therapy (CPT) is recommended for all HIV-exposed infants to avoid opportunistic infections. Cotrimoxazole has antimalarial effects and appears to reduce clinical malaria infections, but the impact on asymptomatic malaria infections is unknown. METHODS: We conducted an observational cohort study using data and dried blood spots (DBS) from the Breastfeeding, Antiretrovirals and Nutrition study to evaluate the impact of CPT on malaria infection during peak malaria season in Lilongwe, Malawi. We compared malaria incidence one year before and after CPT implementation (292 and 682 CPT-unexposed and CPT-exposed infants, respectively), including only infants who remained HIV-negative by 36 weeks of age. Malaria was defined as clinical, asymptomatic (using DBS at 12, 24 and 36 weeks), or a composite outcome of clinical or asymptomatic. Linear and binomial regression with generalized estimating equations were used to estimate the association between CPT and malaria. Differences in characteristics of parasitemias and drug resistance polymorphisms by CPT status were also assessed in the asymptomatic infections. RESULTS: CPT was associated with a 70% (95% CI: 53-81%) relative reduction in the risk of asymptomatic infection between 6-36 weeks of age. CPT appeared to provide temporary protection against clinical malaria and more sustained protection against asymptomatic infections, with no difference in parasitemia characteristics. CONCLUSIONS: CPT appears to reduce overall malaria infections with more prolonged impacts on asymptomatic infections. Asymptomatic infections are potentially important reservoirs for malaria transmission. Therefore, CPT prophylaxis may have important individual and public health benefits. |
Antiretroviral treatment is associated with iron deficiency in HIV-infected Malawian women that is mitigated with supplementation, but is not associated with infant iron deficiency during 24 weeks of exclusive breastfeeding
Widen EM , Bentley ME , Chasela CS , Kayira D , Flax VL , Kourtis AP , Ellington SR , Kacheche Z , Tegha G , Jamieson DJ , van der Horst CM , Allen LH , Shahab-Ferdows S , Adair LS . J Acquir Immune Defic Syndr 2015 69 (3) 319-28 OBJECTIVE: In resource-limited settings without safe alternatives to breastfeeding, the WHO recommends exclusive breastfeeding and antiretroviral (ARV) prophylaxis. Given the high prevalence of anemia among HIV-infected women, mothers and their infants (via fetal iron accretion) may be at risk of iron deficiency. We assessed the effects of maternal micronutrient-fortified lipid-based nutrient supplements (LNS) and maternal ARV treatment or infant ARV prophylaxis on maternal and infant iron status during exclusive breastfeeding from birth to 24 weeks. METHODS: The Breastfeeding, Antiretrovirals, and Nutrition Study was a randomized controlled trial conducted in Lilongwe, Malawi from 2004-2010. HIV-infected mothers (CD4>200 cells/ul) and their infants were randomly assigned to 28-week interventions: maternal-LNS/maternal-ARV (n=424), maternal-LNS/infant-ARV (n=426), maternal-LNS (n=334), maternal-ARV (n=425), infant-ARV (n=426), or control (n=334). Longitudinal models tested intervention effects on hemoglobin (Hb). In a subsample (n=537) with multiple iron indicators, intervention effects on Hb, transferrin receptors (TfR) and ferritin were tested with linear and Poisson regression. RESULTS: In longitudinal models, LNS effects on maternal and infant Hb were minimal. In subsample mothers, maternal ARVs were associated with tissue iron depletion (TfR>8.3 mg/L) (Risk ratio (RR): 3.1, p<0.01), but not in ARV-treated mothers receiving LNS (p=0.17). LNS without ARVs, was not associated with iron deficiency or anemia (p>0.1). In subsample infants, interventions were not associated with impaired iron status (all p-values>0.1). CONCLUSIONS: Maternal ARV treatment with protease inhibitors is associated with maternal tissue iron depletion; but LNS mitigates adverse effects. ARVs do not appear to influence infant iron status; however, extended use needs to be evaluated. |
Dietary patterns and maternal anthropometry in HIV-infected, pregnant Malawian women
Ramlal RT , Tembo M , King CC , Ellington S , Soko A , Chigwenembe M , Chasela C , Jamieson DJ , van der Horst C , Bentley M , Adair L , The Ban Study Team . Nutrients 2015 7 (1) 584-94 Diet is a modifiable factor that can contribute to the health of pregnant women. In a sample of 577 HIV-positive pregnant women who completed baseline interviews for the Breastfeeding, Antiretrovirals, and Nutrition Study in Lilongwe, Malawi, cluster analysis was used to derive dietary patterns. Multiple regression analysis was used to identify associations between the dietary patterns and mid-upper arm circumference (MUAC), arm muscle area (AMA), arm fat area (AFA), and hemoglobin at baseline. Three key dietary patterns were identified: animal-based, plant-based, and grain-based. Women with relatively greater wealth were more likely to consume the animal-based diet, which had the highest intake of energy, protein, and fat and was associated with higher hemoglobin levels compared to the other diets. Women with the lowest wealth were more likely to consume the grain-based diet with the lowest intake of energy, protein, fat, and iron and were more likely to have lower AFA than women on the animal-based and plant-based diets, but higher AMA compared to women on the animal-based diet. Pregnant, HIV-infected women in Malawi could benefit from nutritional support to ensure greater nutrient diversity during pregnancy, when women face increased nutrient demands to support fetal growth and development. |
Reducing lost to follow-up in a large clinical trial of prevention of mother-to-child transmission of HIV: the Breastfeeding, Antiretrovirals and Nutrition study experience
Sellers CJ , Lee H , Chasela C , Kayira D , Soko A , Mofolo I , Ellington S , Hudgens MG , Kourtis AP , King CC , Jamieson DJ , van der Horst C . Clin Trials 2014 12 (2) 156-65 BACKGROUND/AIMS: Retaining patients in prevention of mother-to-child transmission of HIV studies can be challenging in resource-limited settings, where high lost to follow-up rates have been reported. In this article, we describe the effectiveness of methods used to encourage retention in the Breastfeeding, Antiretrovirals, and Nutrition study and analyze factors associated with lost to follow-up in the study. METHODS: The Breastfeeding, Antiretrovirals, and Nutrition clinical trial was designed to evaluate the efficacy of three different mother-to-child HIV transmission prevention strategies. Lower than expected participant retention prompted enhanced efforts to reduce lost to follow-up during the conduct of the trial. Following study completion, we employed regression modeling to determine predictors of perfect attendance and variables associated with being lost to follow-up. RESULTS: During the study, intensive tracing efforts were initiated after the first 1686 mother-infant pairs had been enrolled, and 327 pairs were missing. Of these pairs, 60 were located and had complete data obtained. Among the 683 participants enrolling after initiation of intensive tracing efforts, the lost to follow-up rate was 3.4%. At study's end, 290 (12.2%) of the 2369 mother-infant pairs were lost to follow-up. Among successfully traced missing pairs, relocation was common and three were deceased. Log-binomial regression modeling revealed higher maternal hemoglobin and older maternal age to be significant predictors of perfect attendance. These factors and the presence of food insecurity were also significantly associated with lower rates of lost to follow-up. CONCLUSION: In this large HIV prevention trial, intensive tracing efforts centered on reaching study participants at their homes succeeded in finding a substantial proportion of lost to follow-up participants and were very effective in preventing further lost to follow-up during the remainder of the trial. The association between food insecurity and lower rates of lost to follow-up is likely related to the study's provision of nutritional support, including a family maize supplement, which may have contributed to patient retention. |
Adherence to extended postpartum antiretrovirals is associated with decreased breast milk HIV-1 transmission
Davis NL , Miller WC , Hudgens MG , Chasela CS , Sichali D , Kayira D , Nelson JA , Stringer JS , Ellington SR , Kourtis AP , Jamieson DJ , van der Horst C . AIDS 2014 28 (18) 2739-2749 OBJECTIVE: Estimate association between postpartum antiretroviral adherence and breast milk HIV-1 transmission. DESIGN: Prospective cohort study. METHODS: Mother-infant pairs were randomized after delivery to immediately begin receiving 28 weeks of either triple maternal antiretrovirals (zidovudine, lamivudine, and either nevirapine, nelfinavir, or lopinavir-ritonavir) or daily infant nevirapine as part of the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study. Associations between postpartum antiretroviral adherence and rate of breast milk HIV-1 transmission were estimated using Cox models. We measured adherence over four postpartum time intervals using pill count, suspension bottle weight, and maternal self-report. Adherence was categorized and lagged by one interval. Missing adherence measures were multiply imputed. Infant HIV-1 infection was determined by DNA PCR every 2-6 weeks. The primary endpoint was infant HIV-1 infection by 38 weeks of age among infants alive and uninfected at 5 weeks. RESULTS: Analyses included 1479 mother-infant pairs and 45 transmission events. Using pill count and bottle weight information, 22-40% of mother-infant pairs at any given interval were less than 90% adherent. Having at least 90% adherence was associated with a 52% [95% confidence interval (CI) 3-76] relative reduction in the rate of breast milk HIV-1 transmission, compared with having less than 90% adherence when controlling for study arm, breastfeeding status, and maternal characteristics. Complete case analysis rendered similar results (n = 501; relative reduction 59%, 95% CI 6-82). CONCLUSION: Nonadherence to extended postpartum antiretroviral regimens in 'real world' settings is likely to be higher than that seen in BAN. Identifying mothers with difficulty adhering to antiretrovirals, and developing effective adherence interventions, will help maximize benefits of antiretroviral provision throughout breastfeeding. |
Changes in soluble transferrin receptor and hemoglobin concentrations in Malawian mothers are associated with those values in their exclusively breastfed, HIV-exposed infants
Widen EM , Bentley ME , Kayira D , Chasela CS , Daza EJ , Kacheche ZK , Tegha G , Jamieson DJ , Kourtis AP , van der Horst CM , Allen LH , Shahab-Ferdows S , Adair LS . J Nutr 2014 144 (3) 367-73 Infant iron status at birth is influenced by maternal iron status during pregnancy; however, there are limited data on the extent to which maternal iron status is associated with infant iron status during exclusive breastfeeding. We evaluated how maternal and infant hemoglobin and iron status [soluble transferrin receptors (TfR) and ferritin] were related during exclusive breastfeeding in HIV-infected women and their infants. The Breastfeeding, Antiretrovirals, and Nutrition Study was a randomized controlled trial in Lilongwe, Malawi, in which HIV-infected women were assigned with a 2 x 3 factorial design to a lipid-based nutrient supplement (LNS), or no LNS, and maternal, infant, or no antiretroviral drug, and followed for 24 wk. Longitudinal models were used to relate postpartum maternal hemoglobin (n = 1926) to concurrently measured infant hemoglobin, adjusting for initial infant hemoglobin values. In a subsample, change in infant iron status (hemoglobin, log ferritin, log TfR) between 2 (n = 352) or 6 wk (n = 167) and 24 wk (n = 519) was regressed on corresponding change in the maternal indicator, adjusting for 2 or 6 wk values. A 1 g/L higher maternal hemoglobin at 12, 18, and 24 wk was associated with a 0.06 g/L (P = 0.01), 0.10 g/L (P < 0.001), and 0.06 g/L (P = 0.01), respectively, higher infant hemoglobin. In the subsample, a reduction in maternal log TfR and an increase in hemoglobin from initial measurement to 24 wk were associated with the same pattern in infant values (log TfR beta = -0.18 mg/L, P < 0.001; hemoglobin beta = 0.13 g/L, P = 0.01). Given the observed influence of maternal and initial infant values, optimizing maternal iron status in pregnancy and postpartum is important to protect infant iron status. This trial was registered at clinicaltrials.gov as NCT00164736. |
Hepatitis B virus infection among HIV-infected pregnant women in Malawi and transmission to infants
Chasela CS , Kourtis AP , Wall P , Drobeniuc J , King CC , Thai H , Teshale EH , Hosseinipour M , Ellington S , Codd MB , Jamieson DJ , Knight R , Fitzpatrick P , Kamili S , Hoffman I , Kayira D , Mumba N , Kamwendo DD , Martinson F , Powderly W , Teo CG , van der Horst C . J Hepatol 2014 60 (3) 508-14 BACKGROUND & AIMS: The extent of HBV infection to infants of HBV/HIV-coinfected pregnant women in sub-Saharan Africa is unknown. The aim of this study was to assess prevalence of HBV infection among antiretroviral-naive, HIV-infected pregnant women in Malawi and examine HBV transmission to their infants. METHODS: Plasma from 2048 HIV-infected, Malawian women and their infants were tested for markers of HBV infection. Study participants were provided standard-of-care health services, which included administration of pentavalent vaccine to infants at 6, 10, and 14weeks of age. RESULTS: One-hundred and three women (5%) were HBsAg-positive; 70 of these HBsAg-positive women were also HBV-DNA-positive. Sixteen women (0.8%) were HBV-DNA-positive but HBsAg-negative. Five of 51 infants (9.8%) born to HBsAg-positive and/or HBV-DNA-positive women were HBV-DNA-positive by 48weeks of age.HBV DNA concentrations of two infants of mothers who received extended lamivudine-containing anti-HIV prophylaxis were <4 log10 IU/ml compared to 8 log10 IU/ml in three infants of mothers who did not. CONCLUSIONS: HBV DNA was detected in nearly 10% of infants born to HBV/HIV-coinfected women. Antenatal testing for HIV and HBV, if instituted, can facilitate implementation of prophylactic measures against infant infection by both viruses. |
Plasma and breast-milk selenium in HIV-infected Malawian mothers are positively associated with infant selenium status but are not associated with maternal supplementation: results of the Breastfeeding, Antiretrovirals, and Nutrition study
Flax VL , Bentley ME , Combs GF Jr , Chasela CS , Kayira D , Tegha G , Kamwendo D , Daza EJ , Fokar A , Kourtis AP , Jamieson DJ , van der Horst CM , Adair LS . Am J Clin Nutr 2014 99 (4) 950-6 BACKGROUND: Selenium is found in soils and is essential for human antioxidant defense and immune function. In Malawi, low soil selenium and dietary intakes coupled with low plasma selenium concentrations in HIV infection could have negative consequences for the health of HIV-infected mothers and their exclusively breastfed infants. OBJECTIVE: We tested the effects of lipid-based nutrient supplements (LNS) that contained 1.3 times the Recommended Dietary Allowance of sodium selenite and antiretroviral drugs (ARV) on maternal plasma and breast-milk selenium concentrations. DESIGN: HIV-infected Malawian mothers in the Breastfeeding, Antiretrovirals, and Nutrition study were randomly assigned at delivery to receive: LNS, ARV, LNS and ARV, or a control. In a subsample of 526 mothers and their uninfected infants, we measured plasma and breast-milk selenium concentrations at 2 or 6 (depending on the availability of infant samples) and 24 wk postpartum. RESULTS: Overall, mean (+/-SD) maternal (range: 81.2 +/- 20.4 to 86.2 +/- 19.9 mug/L) and infant (55.6 +/- 16.3 to 61.0 +/- 15.4 mug/L) plasma selenium concentrations increased, whereas breast-milk selenium concentrations declined (14.3 +/- 11.5 to 9.8 +/- 7.3 mug/L) from 2 or 6 to 24 wk postpartum (all P < 0.001). Compared with the highest baseline selenium tertile, low and middle tertiles were positively associated with a change in maternal plasma or breast-milk selenium from 2 or 6 to 24 wk postpartum (both P < 0.001). With the use of linear regression, we showed that LNS that contained selenium and ARV were not associated with changes in maternal plasma and breast-milk selenium, but maternal selenium concentrations were positively associated with infant plasma selenium at 2 or 6 and 24 wk postpartum (P < 0.001) regardless of the study arm. CONCLUSIONS: Selenite supplementation of HIV-infected Malawian women was not associated with a change in their plasma or breast-milk selenium concentrations. Future research should examine effects of more readily incorporated forms of selenium (ie, selenomethionine) in HIV-infected breastfeeding women. This trial was registered at clinicaltrials.gov as NCT00164736. |
The effect of cotrimoxazole prophylactic treatment on malaria, birth outcomes, and postpartum CD4 count in HIV-infected women
Dow A , Kayira D , Hudgens MG , Van Rie A , King CC , Ellington S , Chome N , Kourtis A , Turner AN , Kacheche Z , Jamieson DJ , Chasela C , van der Horst C . Infect Dis Obstet Gynecol 2013 2013 340702 BACKGROUND: Limited data exist on cotrimoxazole prophylactic treatment (CPT) in pregnant women, including protection against malaria versus standard intermittent preventive therapy with sulfadoxine-pyrimethamine (IPTp). METHODS: Using observational data we examined the effect of CPT in HIV-infected pregnant women on malaria during pregnancy, low birth weight and preterm birth using proportional hazards, logistic, and log binomial regression, respectively. We used linear regression to assess effect of CPT on CD4 count. RESULTS: Data from 468 CPT-exposed and 768 CPT-unexposed women were analyzed. CPT was associated with protection against malaria versus IPTp (hazard ratio: 0.35, 95% Confidence Interval (CI): 0.20, 0.60). After adjustment for time period this effect was not statistically significant (adjusted hazard ratio: 0.66, 95% CI: 0.28, 1.52). Among women receiving and not receiving CPT, rates of low birth weight (7.1% versus 7.6%) and preterm birth (23.5% versus 23.6%) were similar. CPT was associated with lower CD4 counts 24 weeks postpartum in women receiving (-77.6 cells/ mu L, 95% CI: -125.2, -30.1) and not receiving antiretrovirals (-33.7 cells/ mu L, 95% CI: -58.6, -8.8). CONCLUSIONS: Compared to IPTp, CPT provided comparable protection against malaria in HIV-infected pregnant women and against preterm birth or low birth weight. Possible implications of CPT-associated lower CD4 postpartum warrant further examination. |
Role of intestinal mucosal integrity in HIV transmission to infants through breastfeeding: the BAN Study
Kourtis AP , Ibegbu CC , Wiener J , King CC , Tegha G , Kamwendo D , Kumwenda J , Pal KS , Flax V , Ellington S , Kacheche Z , Kayira D , Chasela C , van der Horst C , Jamieson DJ . J Infect Dis 2013 208 (4) 653-61 BACKGROUND: Increased intestinal permeability may be one of the mechanisms of transmission of HIV to the infant through breastfeeding. It correlates with microbial translocation, which can be measured through quantification of bacterial lipopolysaccharide (LPS). METHODS: We evaluated levels of plasma LPS (Limulus Amoebocyte Lysate assay), and immune activation markers in serial specimens of HIV-exposed uninfected and HIV-infected infants from the Breastfeeding, Antiretrovirals and Nutrition (BAN) Study. RESULTS: Plasma LPS levels increased after infants in BAN weaned from the breast at 24 weeks of age. Cotrimoxazole prophylaxis was associated with higher plasma LPS levels (p=0.004). Infants with HIV infection had higher LPS levels compared with uninfected infants (p= 0.004). Pre-infection plasma LPS levels were a significant predictor of infant HIV infection through breastfeeding (HR=1.60 for every unit increase in plasma LPS, p=0.01) and for lower infant length-for-age (p=0.02). CONCLUSIONS: These findings suggest that disruption in intestinal integrity is a mechanism of HIV transmission to the infant through breastfeeding. Weaning from breast milk and use of antibiotic prophylaxis was associated with increased levels of microbial translocation, which could facilitate HIV entry through the intestine. Complementary approaches to enhance intestinal mucosal integrity in the infant may further reduce breastfeeding transmission of HIV. |
Lipid-based nutrient supplements are feasible as a breastmilk replacement for HIV-exposed infants from 24 to 48 weeks of age
Flax VL , Bentley ME , Chasela CS , Kayira D , Hudgens MG , Kacheche KZ , Chavula C , Kourtis AP , Jamieson DJ , van der Horst CM , Adair LS . J Nutr 2013 143 (5) 701-7 The Breastfeeding, Antiretrovirals, and Nutrition (BAN) Study randomized HIV-infected mothers and their infants to receive either maternal lipid-based nutrient supplements (LNS) during lactation or no LNS and then to 1 of 3 antiretroviral drug (ARV) arms (maternal, infant, or no drugs). Assigned interventions were provided from 0 to 28 wk and all infants (n = 1619) were given LNS during (24-28 wk) and following (28-48 wk) weaning. This paper assesses the feasibility of infant LNS as a breastmilk replacement and uses longitudinal random effects models to examine associations of interventions, morbidity, and season with weight-for-age (WAZ), length-for-age (LAZ), and BMI-for-age (BMIZ) Z-scores from 24 to 48 wk. Infant LNS adherence was high (94.1% ate it daily). From 24 to 48 wk, mean WAZ (-0.42 to -0.76 SD; P < 0.001) and LAZ (-0.93 to -1.56 SD; P < 0.001) steadily declined, whereas BMIZ remained >0 throughout. A higher LAZ was associated with assignment to the maternal LNS arm (beta=0.19; P < 0.05). Lower WAZ and BMIZ were associated with seasonal food insecurity (beta=-0.08 and -0.09, respectively; both P < 0.001), fever (beta=-0.07 and -0.13; both P < 0.001), diarrhea (beta=-0.19 and -0.23; both P < 0.001), and assignment to the infant ARV arm (beta=-0.17 and -0.17; both P < 0.05). The magnitude of the season and morbidity effects was small and BAN infants had higher weights and lengths than their counterparts in the general population. High LNS adherence and the modest impact of morbidity on growth indicate that LNS is a feasible breastmilk replacement for HIV-exposed infants weaned early, but controlled trials are needed to quantify the effects of LNS on growth in this population. |
Health outcomes of HIV-exposed uninfected African infants
Kourtis AP , Wiener J , Kayira D , Chasela C , Ellington SR , Hyde L , Hosseinipour M , Van Der Horst C , Jamieson DJ . AIDS 2013 27 (5) 749-759 OBJECTIVES: To evaluate severe (grade 3/4) morbidity and mortality in HIV-exposed, uninfected infants. DESIGN: Secondary data analysis of The Breastfeeding, Antiretrovirals, and Nutrition (BAN) clinical trial. METHODS: BAN randomized 2369 mother-infant pairs to maternal, infant, or no extended antiretroviral prophylaxis during breastfeeding. Morbidity outcomes examined were pneumonia/serious febrile illness, diarrhea/growth faltering, and malaria. Infant death was defined as neonatal (≤30 days of life), and postneonatal (31 days to 48 weeks of life). Cox proportional hazards models were used to evaluate the effect of covariates on infant morbidity and mortality. RESULTS: The rate of pneumonia/serious febrile illness was highest in the first 12 weeks (0.83/100 person-weeks) before rapidly decreasing; rates of all morbidity outcomes increased after 24 weeks. Rates of pneumonia/serious febrile illness and diarrhea/growth faltering were higher during the rainy season. Prophylactic infant cotrimoxazole significantly decreased the rates of all morbidity outcomes. White blood cell (WBC) count less than 9000/microliters at birth was associated with increased diarrhea/growth faltering [adjusted hazard ratio (aHR) 1.73, P1/40.04] and malaria (aHR 2.18, P1/40.02). Low birth weight (2000-2499 g) was associated with neonatal death (aHR 12.3, P<0.001). Factors associated with postneonatal death included rainy season (aHR 4.24, P1/40.002), infant cotrimoxazole (aHR 0.48, P1/40.03), and low infant WBC count at birth (aHR 2.53, P1/40.02). CONCLUSION: Infant morbidity rates increased after 24 weeks, when BAN infants weaned. Introduction of prophylactic cotrimoxazole was associated with reduced rates of morbidity and mortality in HIV-exposed uninfected infants. Unexpectedly, a low WBC count at birth was significantly associated with later infant morbidity and mortality in this cohort. (2013 Wolters Kluwer Health.) |
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