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1.  Risk Reduction Among HIV-Seroconcordant and -Discordant Couples: The Zambia NOW2 Intervention 
AIDS Patient Care and STDs  2014;28(8):433-441.
Heterosexual HIV transmission remains the leading cause of HIV incidence in adult men and women in sub-Saharan Africa. This study assessed whether an HIV risk-reduction intervention would be more likely to increase sexual barrier acceptability and decrease risk behavior when delivered to couples in gender concordant groups or in an individual format. This study also examined the mutual impact of couple members as a source of influence on acceptability, and assessed whether product acceptability, intimate partner violence (IPV), and/or partner communication predicted sexual barrier use. HIV seroconcordant and serodiscordant couples (n=216) were recruited in Lusaka, Zambia, and randomized to a four session gender-concordant intervention. Participants were assessed at baseline, 6, and 12 months. Willingness to use barriers (p=0.012), acceptability (p<0.001), and barrier use (p<0.001) increased over time in both conditions, and were influenced by gender preferences. IPV decreased (p=0.040) and positive communication increased (p<0.001) in both conditions. Individual and gender concordant group sessions achieved similar increases in sexual barrier use following the intervention. Results highlight the influence of partners as well as product acceptability as predictors of sexual barrier use among couples in sub-Saharan Africa. Future prevention studies should consider both product acceptability and partner influence to achieve optimal sexual risk behavior outcomes.
PMCID: PMC4117267  PMID: 24983201
2.  HLA-G 14bp deletion/insertion polymorphism and mother-to-child transmission of HIV 
Tissue antigens  2014;83(3):161-167.
The human leukocyte antigen HLA-G, highly expressed at the maternal-fetal interface, has a pivotal role in mediating immune tolerance. In this study we investigated the influence of HLA-G 14 bp insertion polymorphism in HIV-1 mother-to-child HIV-1 transmission.
The 14 bp insertion polymorphism was analyzed among 99 HIV-1 positive mothers and 329 infants born to HIV-positive mothers in Zambia, among whom vertical transmission status and timing had been determined. HLA-G 14bp insertion polymorphism was detected using a custom TaqMan SNPs genotyping assay. Logistic regression was conducted to examine the associations between HLA-G alleles and the risk of HIV transmission.
The 14bp insertion allele was more frequent in HIV exposed-uninfected infants than in infected infants, and was associated with reduced risk of both in utero and intrapartum HIV transmission, after adjusting for maternal CD4 cell count and plasma viral load. Maternal HLA-G 14bp insertion genotype and HLA-G concordance between mother and child were not associated with the risk of perinatal HIV transmission.
The presence of the 14 bp insertion associates with protection towards in utero and intrapartum HIV infection in children from Zambia, suggesting that HLA-G could be involved in the vertical transmission of HIV.
PMCID: PMC3950813  PMID: 24571474
HIV-1; HLA-G; 14bp insertion/deletion; genetic polymorphism; vertical transmission
3.  Infants and young children feeding practices and nutritional status in two districts of Zambia 
Appropriate feeding is important in improving nutrition and child survival. Documentation of knowledge of caregiver on infant feeding is scanty in Zambia. The aim of this study was to describe feeding practices and nutritional status among infants and young children (IYC) in two districts in Zambia: Kafue and Mazabuka.
A cross-sectional study was conducted between January and March 2006 using both quantitative and qualitative methods. A questionnaire was administered to caregiver of children aged under24 months. Lengths and weights of all children were measured. Focused group discussions were conducted in selected communities to assess parents or guardian knowledge, attitude and practice related to infant feeding.
A total of 634 caregivers (361 from Kafue and 273 from Mazabuka) participated in the study. About 311/618 (54.0%) of the caregiver knew the definition and recommended duration of exclusive breastfeeding (EBF) and when to introduce complementary feeds. Two hundred and fifty-one (81.2%) out of 310 respondents had acquired this knowledge from the health workers. Only 145/481 (30.1%) of the respondents practiced exclusive breastfeeding up to six months with 56/626 (8.9%) of the mothers giving prelacteal feeds. Although 596/629 (94.8%) of the respondents reported that the child does not need anything other than breast milk in the first three days of life, only 318/630 (50.5%) of them considered colostrum to be good. Complementary feeds were introduced early before six months of age and were usually not of adequate quality and quantity. Three hundred and ninety-one (64%) out of 603 caregivers knew that there would be no harm to the child if exclusively breastfed up to six months. Most of the children’s nutritional status was normal with 25/594 (4.2%) severely stunted, 10/596 (1.7%) severely underweight and 3/594 (0.5%) severely wasted.
The caregiver in the communities knew about the recommended feeding practices, but this knowledge did not translate into good practice. Knowing that most of the mothers will breastfeed and have heard about appropriate breastfeeding, is important in the development of sustainable strategies required to improve feeding practices and, thus, nutritional status of children.
PMCID: PMC4351847  PMID: 25750656
Exclusive breastfeeding; Infant feeding practices; Nutritional status
4.  Evaluation of a Density-Based Rapid Diagnostic Test for Sickle Cell Disease in a Clinical Setting in Zambia 
PLoS ONE  2014;9(12):e114540.
Although simple and low-cost interventions for sickle cell disease (SCD) exist in many developing countries, child mortality associated with SCD remains high, in part, because of the lack of access to diagnostic tests for SCD. A density-based test using aqueous multiphase systems (SCD-AMPS) is a candidate for a low-cost, point-of-care diagnostic for SCD. In this paper, the field evaluation of SCD-AMPS in a large (n = 505) case-control study in Zambia is described. Of the two variations of the SCD-AMPS used, the best system (SCD-AMPS-2) demonstrated a sensitivity of 86% (82–90%) and a specificity of 60% (53–67%). Subsequent analysis identified potential sources of false positives that include clotting, variation between batches of SCD-AMPS, and shipping conditions. Importantly, SCD-AMPS-2 was 84% (62–94%) sensitive in detecting SCD in children between 6 months and 1 year old. In addition to an evaluation of performance, an assessment of end-user operability was done with health workers in rural clinics in Zambia. These health workers rated the SCD-AMPS tests to be as simple to use as lateral flow tests for malaria and HIV.
PMCID: PMC4260838  PMID: 25490722
5.  Human Milk Galectin-3 Binding Protein and Breastfeeding-Associated HIV Transmission 
Analysis of milk from 247 HIV-infected Zambian mothers showed that Galectin-3 Binding Protein (Gal3BP) concentrations were significantly higher among HIV-infected mothers who transmitted HIV through breastfeeding (6.51±2.12 ug/mL) than among non-transmitters but were also correlated with higher milk and plasma HIV RNA copies/ml and lower CD4+ cell counts. The association between Gal3BP and postnatal transmission was attenuated after adjustment for milk and plasma HIV load and CD4+ cell counts. This suggests that although milk Gal3BP is a marker of advanced maternal disease, it does not independently modify transmission risk.
PMCID: PMC3907473  PMID: 23899964
HIV transmission; breastfeeding; Galectin-3 Binding Protein; oral transmission
6.  Growth effects of exclusive breastfeeding promotion by peer counsellors in sub-Saharan Africa: the cluster-randomised PROMISE EBF trial 
BMC Public Health  2014;14:633.
In this multi-country cluster-randomized behavioural intervention trial promoting exclusive breastfeeding (EBF) in Africa, we compared growth of infants up to 6 months of age living in communities where peer counsellors promoted EBF with growth in those infants living in control communities.
A total of 82 clusters in Burkina Faso, Uganda and South Africa were randomised to either the intervention or the control arm. Feeding data and anthropometric measurements were collected at visits scheduled 3, 6, 12 and 24 weeks post-partum. We calculated weight-for-length (WLZ), length-for-age (LAZ) and weight-for-age (WAZ) z-scores. Country specific adjusted Least Squares Means with 95% confidence intervals (CI) based on a longitudinal analysis are reported. Prevalence ratios (PR) for the association between peer counselling for EBF and wasting (WLZ < −2), stunting (LAZ < −2) and underweight (WAZ < −2) were calculated at each data collection point.
The study included a total of 2,579 children. Adjusting for socio-economic status, the mean WLZ at 24 weeks were in Burkina Faso −0.20 (95% CI −0.39 to −0.01) and in Uganda −0.23 (95% CI −0.43 to −0.03) lower in the intervention than in the control arm. In South Africa the mean WLZ at 24 weeks was 0.23 (95% CI 0.03 to 0.43) greater in the intervention than in the control arm. Differences in LAZ between the study arms were small and not statistically significant. In Uganda, infants in the intervention arm were more likely to be wasted compared to those in the control arm at 24 weeks (PR 2.36; 95% CI 1.11 to 5.00). Differences in wasting in South Africa and Burkina Faso and stunting and underweight in all three countries were small and not significantly different.
There were small differences in mean anthropometric indicators between the intervention and control arms in the study, but in Uganda and Burkina Faso, a tendency to slightly lower ponderal growth (weight-for-length z-scores) was found in the intervention arms.
Trial registration number NCT00397150
PMCID: PMC4082276  PMID: 24950759
Exclusive breastfeeding promotion; Peer counselling; Child growth; Anthropometry; Stunting; Wasting; Underweight; Undernutrition; Community randomised trial
7.  Early Childhood Infection of Kaposi’s Sarcoma-associated Herpesvirus in Zambian Households: a Molecular Analysis 
Sub-Saharan Africa is endemic for Kaposi’s sarcoma-associated herpesvirus (KSHV) and there is a high rate of early childhood infection; however, the transmission sources are not well characterized. We examined household members as potential KSHV transmission sources to young children in the KSHV-endemic country of Zambia. To this end, we enrolled and followed Zambian households with at least one KSHV-seropositive child and collected longitudinal buccal swab samples. KSHV burden was evaluated and K1 sequences from the children were determined and analyzed for differences to K1 sequences from household members. The K1 sequences were also analyzed for evolution over time. We generated K1 sequences from 31 individuals across 16 households. Nine households contained multiple KSHV-positive members, including at least one child. In 6 of 9 households, the child had 100% sequence identity to all household members. However, in two households the child and mother had distinct K1 sequences. In the remaining household, the children were the only KSHV-infected individuals. Furthermore, we report that 1 of 18 individuals had K1 sequence variation within the timespan analyzed. In the present study, we provide evidence that (1) early childhood KSHV transmission occurs from both within and outside the household, (2) intra-household transmission can occur via non-maternal sources, (3) viral shedding in the buccal cavity is highly variable, and (4) the dominant K1 sequence within an individual did not rapidly evolve over time. These results are important for developing KSHV intervention strategies.
PMCID: PMC3535687  PMID: 22815207
Kaposi’s sarcoma-associated herpesvirus; children; households; Zambia; K1; transmission
8.  Dynamics of breast milk HIV-1 RNA with unilateral mastitis or abscess 
Mastitis and abscess in HIV-infected women increase risk of breastfeeding transmission of HIV. Guidelines encourage women to stop breastfeeding on the affected breast and feed on the contralateral breast. However, impact of breast pathology on breast milk HIV dynamics is unknown.
HIV RNA was quantified in 211 breast milk samples collected before, during and after a clinical mastitis or abscess diagnosis from 38 HIV-infected women participating in a Zambian breastfeeding study. HIV RNA quantity was compared between affected and unaffected breasts over time using generalized estimating equation models. A sample of 115 women without breast pathology was selected as a control group.
In the affected breast, breast milk HIV RNA quantity increased from the pre- to during-pathology period by log10 0.45 copies/mL (95% CI: 0.16, 0.74) and after symptom resolution, HIV RNA levels were no different from pre-pathology levels (log10 -0.04 copies/mL 95%CI: -0.33, 0.25). In the contralateral unaffected breast, HIV RNA quantity did not significantly increase (log10 0.15 copies/mL, 95% CI: -0.41, 0.10). Increase was more marked in women with abscess or with a greater number of mastitis symptoms. HIV RNA was not significantly different between affected and unaffected women, except at the time of diagnosis.
Breast milk HIV RNA increased modestly in the affected breast with unilateral mastitis or abscess and returned to pre-pathology levels with symptom resolution. Contralateral HIV RNA was not affected. Results support guidelines encouraging feeding from the contralateral breast to minimize risk of HIV transmission associated with unilateral breast pathology.
PMCID: PMC3647002  PMID: 23202812
Infant feeding; HIV; Exclusive breastfeeding; Breast problem; Mastitis; Abscess
9.  Pediatric Malignancies, Treatment Outcomes and Abandonment of Pediatric Cancer Treatment in Zambia 
PLoS ONE  2014;9(2):e89102.
There exist significant challenges to the receipt of comprehensive oncologic treatment for children diagnosed with cancer in sub-Saharan Africa. To better define those challenges, we investigated treatment outcomes and risk factors for treatment abandonment in a cohort of children diagnosed with cancer at the University Teaching Hospital (UTH), the site of the only pediatric oncology ward in Zambia.
Using an established database, a retrospective cohort study was conducted of children aged 0–15 years admitted to the pediatric oncology ward between July 2008 and June 2010 with suspected cancer. Diagnosis, mode of diagnosis, treatment outcome, and risk factors for abandonment of treatment were abstracted from this database and clinical medical records.
Among 162 children treated at the UTH during the study time period that met inclusion criteria, only 8.0% completed a treatment regimen with most of the patients dying during treatment or abandoning care. In multivariable analysis, shorter distance from home to the UTH was associated with a lower risk of treatment abandonment (Adjusted Odds Ratio [aOR] = 0.48 (95% confidence interval [CI] 0.23–0.97). Conversely maternal education less than secondary school was associated with increased risk for abandonment (aOR = 1.65; 95% CI 1.05–2.58).
Despite availability of dedicated pediatric oncology treatment, treatment completion rates are poor, due in part to the logistical challenges faced by families, low educational status, and significant distance from the hospital. Alternative treatment delivery strategies are required to bring effective pediatric oncology care to the patients in need, as their ability to come to and remain at a central tertiary care facility for treatment is limited. We suggest that the extensive system now in place in most of sub-Saharan Africa that sustains life-long antiretroviral therapy for children with human immunodeficiency virus (HIV) infection be adapted for pediatric cancer treatment to improve outcome.
PMCID: PMC3931678  PMID: 24586527
10.  Coverage of primary mother-to-child HIV transmission isolates by second-generation broadly neutralizing antibodies 
AIDS (London, England)  2013;27(3):10.1097/QAD.0b013e32835cadd6.
Objectives and design
A vaccine capable of providing cross-clade, sterilizing protection has been the holy grail of HIV-1 prevention and control since the beginning of the pandemic. A major component of this effort has been the identification and characterization of broadly neutralizing antibodies (bNAbs). Recent advances in bNAb isolation, structure-based engineering, and vector-mediated gene transfer have led to increased interest in bypassing the immune system by expressing neutralizing antibodies directly in muscle. To assess the neutralization potency and coverage of a panel of second-generation bNAbs, we cloned and phenotypically characterized 227 primary HIV-1 envelopes from 23 mother-to-child transmission (MTCT) pairs.
Viral envelopes were tested for in-vitro neutralization sensitivity using a standard pseudotype assay system. A 50% inhibitory concentration (IC50) at least 10 μg/ml was used to define neutralization resistance.
The combination of antibodies PG16 and NIH45–46G54W had the broadest activity with the highest neutralization potency, achieving full coverage of 87% of transmission pairs (at a median sampling depth of 10 envelopes per pair) and 96% of recently infected infants in a very conservative analysis.
Our data strongly support the inclusion of NIH45–46G54W, or a more extensively modified variant, in future proof-of-principle immunoprophylaxis or gene therapy-based trials. Furthermore, until robust sequence-based resistance detection becomes available, it will be necessary to conduct deeper phenotypic screening of primary isolates in order to determine the prevalence of minor resistant variants to help in selecting the best reagents for clinical trials.
PMCID: PMC3863550  PMID: 23296195
AIDS; antibodies; HIV; neutralization; paediatrics; prevention of mother-to-child transmission; vaccine
11.  Higher Levels of Neutralizing Antibodies against KSHV in KS Patients Compared to Asymptomatic Individuals from Zambia 
PLoS ONE  2013;8(8):e71254.
Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi Sarcoma (KS), the most common cancer diagnosed in HIV- infected patients. The role of neutralizing antibodies in KS pathogenesis and in KSHV infected individuals is not clearly understood. The goal of this study was to investigate and compare the prevalence and titers of neutralizing antibodies in plasma samples from KS patients and KSHV infected asymptomatic individuals from Zambia, a KS endemic region in sub-Saharan Africa. Plasma samples (N = 267) consisting of KS patients (group 1) and asymptomatic individuals (group 2) were collected from Lusaka, Zambia. A flow cytometry based quantitative neutralization assay utilizing recombinant KSHV expressing GFP was used to detect KSHV neutralizing antibodies. Our results show that the overall prevalence of neutralizing antibodies in KS patients (group 1) was 66.7% which was significantly higher than the prevalence of 6.5% present in KSHV infected asymptomatic individuals (group 2). Total antibody titers as well as neutralizing antibodies titers were found to be significantly higher among KS patients. It is likely that higher neutralizing antibodies prevalence and titers in KS patients result from higher levels of antigenic stimulation over time. This study is first to compare prevalence and titers of neutralizing antibodies in participants with and without disease from a KSHV endemic region.
PMCID: PMC3743886  PMID: 23967174
12.  Performance of modified WHO presumptive criteria for diagnosis of HIV infection in children <18 months admitted to University Teaching Hospital in Lusaka 
Medical journal of Zambia  2010;37(2):64-70.
Making a diagnosis of HIV infection in children aged less than 18 months remains a challenge in low resource settings like Zambia due to the limited availability of gold standard testing with HIV DNA PCR. Clinicians in rural areas have to depend on clinical diagnosis to start HAART as they wait for the dry blood spot (DBS) for DNA PCR results sent from the urban centers.
This descriptive cross-sectional study was performed at the University Teaching Hospital, Lusaka, Zambia. 299 HIV-exposed children aged less than 18 months were enrolled following a consent procedure. Patients were evaluated for HIV infection based on the World Health Organization’s presumptive diagnostic criteria (WHO-PDC), integrated management of childhood illnesses (IMCI) criteria, select physical exam abnormalities, and CD4% and findings were compared with HIV-DNA PCR results.
Of the 299 exposed patients analyzed, 111(37%) were found to be HIV-positive by DNA PCR. The median CD4% in the infected children was 18%. WHO-PDC used on its own had 23% sensitivity (95% CI 17–32%) and 93% specificity (88–96%), respectively, whereas IMCI criterion had 10% sensitivity (6–17%) and 97% specificity (94–99%), respectively. Multivariate analysis was used to identify the most sensitive predictors when combined with the WHO-PDC and IMCI criterion. WHO-PDC with CD4% improved the sensitivity to 77% (68–83%) with a specificity of 83% (77–88%), positive predictive value (PPV) of 73% (64–80%) and negative predictive value (NPV) of 86% (80–90%). IMCI with CD4% improved sensitivity to 80% (71–87%) with a specificity of 88% (82–92%), PPV 78% (69–85%) and NPV 89% (84–93%). The addition of individual physical exam findings without CD4% improved the sensitivity of WHO-PDC only modestly. When the WHO-PDC, weight<3rd percentile, hepatomegaly, splenomegaly, lymphadenopathy and CD4% were combined, the sensitivity improved to 85% (77–90%), specificity 63% (56–70%), PPV 58% (50–65%) and NPV of 88% (81–92%).
The WHO-PDC clinical algorithm can be improved when combined with a CD4% <25% in children less than 12 months of age and CD4% <20% in those between 12 and 18 months.
PMCID: PMC3500600  PMID: 23170039
HIV; early infant diagnosis; diagnosis; Zambia
13.  Lopinavir/Ritonavir versus Lamivudine peri-exposure prophylaxis to prevent HIV-1 transmission by breastfeeding: the PROMISE-PEP trial Protocol ANRS 12174 
BMC Infectious Diseases  2012;12:246.
Postnatal transmission of HIV-1 through breast milk remains an unsolved challenge in many resource-poor settings where replacement feeding is not a safe alternative. WHO now recommends breastfeeding of infants born to HIV-infected mothers until 12 months of age, with either maternal highly active antiretroviral therapy (HAART) or peri-exposure prophylaxis (PEP) in infants using nevirapine. As PEP, lamivudine showed a similar efficacy and safety as nevirapine, but with an expected lower rate of resistant HIV strains emerging in infants who fail PEP, and lower restrictions for future HIV treatment. Lopinavir/ritonavir (LPV/r) is an attractive PEP candidate with presumably higher efficacy against HIV than nevirapine or lamivudine, and a higher genetic barrier to resistance selection. It showed an acceptable safety profile for the treatment of very young HIV-infected infants. The ANRS 12174 study aims to compare the risk of HIV-1 transmission during and safety of prolonged infant PEP with LPV/r (40/10 mg twice daily if 2-4 kg and 80/20 mg twice daily if >4 kg) versus Lamivudine (7,5 mg twice daily if 2-4 kg, 25 mg twice daily if 4-8 kg and 50 mg twice daily if >8 kg) from day 7 until one week after cessation of BF (maximum 50 weeks of prophylaxis) to prevent postnatal HIV-1 acquisition between 7 days and 50 weeks of age.
The ANRS 12174 study is a multinational, randomised controlled clinical trial conducted on 1,500 mother-infant pairs in Burkina Faso, South Africa, Uganda and Zambia. We will recommend exclusive breastfeeding (EBF) until 26th week of life and cessation of breastfeeding at a maximum of 49 weeks in both trial arms.
HIV-uninfected infants at day 7 (± 2 days) born to HIV-1 infected mothers not eligible for HAART who choose to breastfeed their infants.
The primary endpoint is the acquisition of HIV-1 (as assessed by HIV-1 DNA PCR) between day 7 and 50 weeks of age. Secondary endpoints are safety (including resistance, adverse events and growth) until 50 weeks and HIV-1-free survival until 50 weeks.
This study will provide a new evidence-based intervention to support HIV-1-infected women not eligible for HAART to safely breastfeed their babies.
Trial registration number (
PMCID: PMC3482558  PMID: 23039034
14.  Exclusive breastfeeding, maternal HIV disease, and the risk of clinical breast pathology in HIV-infected, breastfeeding women 
To examine the relationship between breastfeeding patterns, markers of maternal HIV disease, and woman’s breast pathology.
Study Design
Secondary data analysis from a randomized breastfeeding trial including 947 HIV-infected women (n=5,982 visits) from breastfeeding initiation until: 6 months post-partum; 1 month after breastfeeding cessation; or loss-to-follow-up/death. Generalized estimating equations assessed the effects of breastfeeding pattern and maternal HIV status on breast pathology.
190 (20.1%) women had a breast problem; 86 (9.1%) had mastitis and 31 (3.3%) had abscess. After confounder adjustment, non-exclusively breastfeeding women increased risk of breast problems (OR: 1.98 95% CI: 1.33, 2.95) and mastitis (OR: 2.87 95% CI: 1.69, 4.88) compared to exclusive breastfeeders. Women with CD4 count <200 cells/uL tended to have increased risk of abscess.
Non-exclusive breastfeeding significantly increased the risk of breast pathology. Exclusive breastfeeding is not only optimal for infant health; it benefits mothers by reducing breast problems.
PMCID: PMC3217158  PMID: 21784403
Abscess; CD4 count; Exclusive breastfeeding; HIV; Mastitis
15.  Pregnancy loss and role of infant HIV status on perinatal mortality among HIV-infected women 
BMC Pediatrics  2012;12:138.
HIV-infected women, particularly those with advanced disease, may have higher rates of pregnancy loss (miscarriage and stillbirth) and neonatal mortality than uninfected women. Here we examine risk factors for these adverse pregnancy outcomes in a cohort of HIV-infected women in Zambia considering the impact of infant HIV status.
A total of 1229 HIV-infected pregnant women were enrolled (2001–2004) in Lusaka, Zambia and followed to pregnancy outcome. Live-born infants were tested for HIV by PCR at birth, 1 week and 5 weeks. Obstetric and neonatal data were collected after delivery and the rates of neonatal (<28 days) and early mortality (<70 days) were described using Kaplan-Meier methods.
The ratio of miscarriage and stillbirth per 100 live-births were 3.1 and 2.6, respectively. Higher maternal plasma viral load (adjusted odds ratio [AOR] for each log10 increase in HIV RNA copies/ml = 1.90; 95% confidence interval [CI] 1.10–3.27) and being symptomatic were associated with an increased risk of stillbirth (AOR = 3.19; 95% CI 1.46–6.97), and decreasing maternal CD4 count by 100 cells/mm3 with an increased risk of miscarriage (OR = 1.25; 95% CI 1.02–1.54). The neonatal mortality rate was 4.3 per 100 increasing to 6.3 by 70 days. Intrauterine HIV infection was not associated with neonatal morality but became associated with mortality through 70 days (adjusted hazard ratio = 2.76; 95% CI 1.25–6.08). Low birth weight and cessation of breastfeeding were significant risk factors for both neonatal and early mortality independent of infant HIV infection.
More advanced maternal HIV disease was associated with adverse pregnancy outcomes. Excess neonatal mortality in HIV-infected women was not primarily explained by infant HIV infection but was strongly associated with low birth weight and prematurity. Intrauterine HIV infection contributed to mortality as early as 70 days of infant age. Interventions to improve pregnancy outcomes for HIV-infected women are needed to complement necessary therapeutic and prophylactic antiretroviral interventions.
PMCID: PMC3480840  PMID: 22937874
Perinatal mortality; Infant mortality; Risk factors; Adverse pregnancy outcome; HIV infection; Vertical transmission
16.  Early Weaning Increases Diarrhea Morbidity and Mortality Among Uninfected Children Born to HIV-infected Mothers in Zambia 
The Journal of Infectious Diseases  2011;203(9):1222-1230.
Background. Early weaning may reduce human immunodeficiency virus (HIV) transmission but may have deleterious consequences for uninfected children. Here we evaluate effects of early weaning on diarrhea morbidity and mortality of uninfected children born to HIV-infected mothers.
Methods. HIV-infected women in Lusaka, Zambia, were randomly assigned to breastfeeding for 4 months only or to continue breastfeeding until the mother decided to stop. Replacement and complementary foods were provided and all women were counseled around feeding and hygiene. Diarrhea morbidity and mortality were assessed in 618 HIV-uninfected singletons alive and still breastfeeding at 4 months. Intent-to-treat analyses and comparisons based on actual feeding practices were conducted using regression methods.
Results. Between 4 and 6 months, diarrheal episodes were 1.8-fold (95% confidence interval (CI), 1.3–2.4) higher in the short compared with long breastfeeding group. Associations were stronger based on actual feeding practices and persisted after adjustment for confounding. At older ages, only more severe outcomes, including diarrhea-related hospitalization or death (relative hazard [RH], 3.2, 95% CI, 2.1–5.1 increase 4–24 months), were increased among weaned children.
Conclusions. Continued breastfeeding is associated with reduced risk of diarrhea-related morbidity and mortality among uninfected children born to HIV-infected mothers in this low-resource setting despite provision of replacement and complementary food and counseling.
 Clinical Trials Registration. NCT00310726.
PMCID: PMC3069726  PMID: 21459815
17.  The Zambia Children's KS-HHV8 Study: Rationale, Study Design, and Study Methods 
American Journal of Epidemiology  2011;173(9):1085-1092.
The epidemic of human immunodeficiency virus in Zambia has led to a dramatic rise in the incidence of human herpesvirus-8 (HHV-8)–associated Kaposi's sarcoma in both adults and children. However, there is a paucity of knowledge about the routes of HHV-8 transmission to young children. The Zambia Children's KS-HHV8 Study, a large, prospective cohort study in Lusaka, Zambia, was launched in 2004 to investigate the role of household members as a source of HHV-8 infection in young children and social behaviors that may modify the risk of HHV-8 acquisition. This cohort is distinct from other epidemiologic studies designed to investigate HHV-8 incidence and transmission because it recruited and followed complete households in the urban central African context. Between July 2004 and March 2007, 1,600 households were screened; 368 households comprising 464 children and 1,335 caregivers and household members were enrolled. Follow-up of this population continued for 48 months postrecruitment, affording a unique opportunity to study horizontal transmission of HHV-8 and understand the routes and sources of transmission to young children in Zambia. The authors describe the study rationale, design, execution, and characteristics of this cohort, which provides critical data on the epidemiology and transmission of HHV-8 to young children in Zambia.
PMCID: PMC3121218  PMID: 21447476
cohort studies; herpesvirus 8, human; incidence; sarcoma, Kaposi; Zambia
18.  Multiple independent lineages of HIV-1 persist in breast milk and plasma 
AIDS (London, England)  2011;25(2):143-152.
The origin and evolution of HIV-1 in breast milk is unclear, despite the continuing significance of this tissue as a transmitting compartment. To elucidate the evolutionary trajectory of viral populations in a transient mucosal compartment, longitudinal sequences of the envelope gp120 region from plasma and breast milk spanning the first year after delivery were analyzed in six women infected by HIV-1 subtype C.
Multiple phylogenetic algorithms were used to elucidate the evolutionary history and spatial structure of virus populations between tissues.
Overall persistent mixing of viral sequences between plasma and breast milk indicated that breast milk is not a distinct genetic viral compartment. Unexpectedly, longitudinal phylogenies showed multiple lineages defined by long branches that included virus from both the breast milk and the plasma. Plasma was unlikely the anatomical origin of the most recent common ancestor (MRCA) in at least three of the subjects, while in other women, the temporal origin of the MRCA of the viral populations following delivery occurred well before the onset of breast milk production.
These findings suggest that during pregnancy/lactation, a viral variant distinct from the plasma virus initially seeds the breast milk, followed by subsequent gene flow between the plasma and breast milk tissues. This study indicates the potential for reactivation or re-introduction of distinct lineages during major immunological disruptions during the course of natural infection.
PMCID: PMC3032216  PMID: 21173592
HIV-1; breast milk; evolution; phylogeny; compartment; reservoir
19.  Lactation-associated postpartum weight changes among HIV-infected women in Zambia 
Background There are concerns about effects of lactation on postpartum weight changes among HIV-infected women because low weight may increase risks of HIV-related disease progression.
Methods This analysis of postpartum maternal weight change is based on a trial evaluating the effects of shortened breastfeeding on postpartum mother-to-child transmission of HIV in Lusaka, Zambia, in which 958 HIV-infected women were randomized to breastfeed for a short duration (4 months) or for a duration of their own informed choosing (median 16 months). Among 768 women who met inclusion criteria, we compared across the two groups change in weight (kg) and the percent underweight [body mass index (BMI) <18.5] through 24 months. We also examined the effect of breastfeeding in two high-risk groups: those with low BMI and those with low CD4 counts.
Results Overall, women in the long-duration group gained less weight compared with those in the short-duration group from 4–24 months {1.0 kg [95% confidence interval (CI): 0.3–1.7] vs 2.3 kg (95% CI: 1.6–2.9), P = 0.01}. No association was found between longer breastfeeding and being underweight (odds ratio 1.1; 95% CI: 0.8–1.6; P = 0.40). Effects of lactation in underweight women and women with low CD4 counts were similar to the effects in women with higher BMI and higher CD4 counts. Women with low baseline BMI tended to gain more weight from 4 to 24 months than those with higher BMI, regardless of breastfeeding duration (2.1 kg, 95% CI: 1.3–2.9; P < 0.01).
Conclusions In this study of HIV-infected breastfeeding women in a low-resource setting, the average change in weight from 4 to 24 months postpartum was a net gain rather than loss. Although longer duration breastfeeding was associated with less weight gain, breastfeeding duration was not associated with being underweight (BMI < 18.5). Weight change associated with longer breastfeeding may be metabolically regulated so that women with low BMI and at risk of wasting are protected from excess weight loss.
PMCID: PMC2972438  PMID: 20484334
Breast feeding; lactation; HIV infections; weight loss; metabolism; body mass index
20.  Effect of using HIV and infant feeding counselling cards on the quality of counselling provided to HIV positive mothers: a cluster randomized controlled trial 
Counselling human immunodeficiency virus (HIV) positive mothers on safer infant and young child feeding (IYCF) options is an important component of programmes to prevent mother to child transmission of HIV, but the quality of counselling is often inadequate. The aim of this study was to determine the effect the World Health Organization HIV and infant feeding cards on the quality of counselling provided to HIV positive mothers by health workers about safer infant feeding options.
This was a un-blinded cluster-randomized controlled field trial in which 36 primary health facilities in Kafue and Lusaka districts in Zambia were randomized to intervention (IYCF counselling with counselling cards) or non- intervention arm (IYCF counselling without counselling cards). Counselling sessions with 10 HIV positive women attending each facility were observed and exit interviews were conducted by research assistants.
Totals of 180 women in the intervention group and 180 women in the control group were attended to by health care providers and interviewed upon exiting the health facility. The health care providers in the intervention facilities more often discussed the advantages of disclosing their HIV status to a household member (RR = 1.46, 95% CI [1.11, 1.92]); used visual aids in explaining the risk of HIV transmission through breast milk (RR = 4.65, 95% CI [2.28, 9.46]); and discussed the advantages and disadvantages of infant feeding options for HIV positive mothers (all p values < 0.05). The differences also included exploration of the home situation (p < 0.05); involving the partner in the process of choosing a feeding option (RR = 1.38, 95% CI [1.09, 1.75]); and exploring how the mother will manage to feed the baby when she is at work (RR = 2.82, 95% CI [1.70, 4.67]). The clients in the intervention group felt that the provider was more caring and understanding (RR = 1.81, 95% CI [1.19, 2.75]).
The addition of counselling cards to the IYCF counselling session for HIV positive mothers were a valuable aid to counselling and significantly improved the quality of the counselling session.
PMCID: PMC3189093  PMID: 21943308
infant feeding; breastfeeding; young children feeding; HIV; counselling cards
21.  Short Communication: Antiretroviral Therapy Resistance Mutations Present in the HIV Type 1 Subtype C pol and env Regions from Therapy-Naive Patients in Zambia 
The prevalence of antiretroviral therapy (ART) resistance mutations present in HIV-1 subtype C pol and env regions of the proviral DNA was analyzed and compared from therapy-naive individuals before (Cohort A) and after (Cohort B) the availability of free ART in Zambia. Mutations present in sequences published in a previous study from Zambian ART-naive individuals infected with subtype C were analyzed using current parameters for the classification of ART drug resistance and compared with Cohorts A and B. No statistically significant differences were observed when comparing mutations present in the pol and env of these cohorts. However, an increase in the number of minor, borderline, or partial resistance mutations as well as the presence of major resistance mutations were observed in Cohort B. These results suggest there is an increasing trend of drug resistance-associated mutations that could be a result of the availability of free ART in Zambia. Moreover, the high prevalence of resistance mutations observed for maraviroc and vicriviroc in both cohorts may suggest a limited efficacy of entry inhibitors on HIV-1 subtype C.
PMCID: PMC2932558  PMID: 20623996
22.  Cost of individual peer counselling for the promotion of exclusive breastfeeding in Uganda 
Exclusive breastfeeding (EBF) for 6 months is the recommended form of infant feeding. Support of mothers through individual peer counselling has been proved to be effective in increasing exclusive breastfeeding prevalence. We present a costing study of an individual peer support intervention in Uganda, whose objective was to raise exclusive breastfeeding rates at 3 months of age.
We costed the peer support intervention, which was offered to 406 breastfeeding mothers in Uganda. The average number of counselling visits was about 6 per woman. Annual financial and economic costs were collected in 2005-2008. Estimates were made of total project costs, average costs per mother counselled and average costs per peer counselling visit. Alternative intervention packages were explored in the sensitivity analysis. We also estimated the resources required to fund the scale up to district level, of a breastfeeding intervention programme within a public health sector model.
Annual project costs were estimated to be US$56,308. The largest cost component was peer supporter supervision, which accounted for over 50% of total project costs. The cost per mother counselled was US$139 and the cost per visit was US$26. The cost per week of EBF was estimated to be US$15 at 12 weeks post partum. We estimated that implementing an alternative package modelled on routine public health sector programmes can potentially reduce costs by over 60%. Based on the calculated average costs and annual births, scaling up modelled costs to district level would cost the public sector an additional US$1,813,000.
Exclusive breastfeeding promotion in sub-Saharan Africa is feasible and can be implemented at a sustainable cost. The results of this study can be incorporated in cost effectiveness analyses of exclusive breastfeeding promotion programmes in sub-Saharan Africa.
PMCID: PMC3135543  PMID: 21714877
23.  Potential impact of new World Health Organization criteria for antiretroviral treatment for prevention of mother-to-child HIV transmission 
AIDS (London, England)  2010;24(9):1374-1377.
We reviewed the potential impact of new World Health Organization criteria for antiretroviral therapy using data from 1025 HIV-infected women and infants followed through 24 months in Lusaka, Zambia. The new criteria require initiating therapy among 68% of pregnant women and, if fully effective, would prevent 92% of maternal deaths and 88% of perinatal and postnatal infections. Using CD4 <350 cells/uL, irrespective of clinical stage, is more efficient and stricter CD4 cut-offs would be counter-productive.
PMCID: PMC2946203  PMID: 20568677
24.  Functional Properties of the HIV-1 Subtype C Envelope Glycoprotein Associated with Mother-to-Child Transmission 
Virology  2010;400(2):164-174.
Understanding the properties of viruses capable of establishing infection during perinatal transmission of HIV-1 is critical for designing effective means of limiting transmission. We previously demonstrated that the newly transmitted viruses (in infant) were more fit in growth, as imparted by their envelope glycoproteins, than those in their corresponding mothers. Here, we further characterized the viral envelope glycoproteins from six mother-infant transmission pairs and determined whether any specific envelope functions correlate with HIV-1 subtype C perinatal transmission. We found that most newly transmitted viruses were less susceptible to neutralization by their maternal plasma compared to contemporaneous maternal viruses. However, the newly transmitted variants were sensitive to neutralization by pooled heterologous plasma but in general were resistant to IgG1 b12. Neither Env processing nor incorporation efficiency was predictive of viral transmissibility. These findings provide further insight into the characteristics of perinatally transmissible HIV-1 and may have implications for intervention approaches.
PMCID: PMC2844456  PMID: 20096914
HIV-1 subtype C; perinatal transmission; envelope glycoproteins; neutralization; autologous or heterologous antibodies; envelope processing and incorporation
25.  Elevations in mortality due to weaning persist into the second year of life among uninfected children born to HIV-infected mothers 
Early weaning has been recommended to reduce postnatal HIV transmission. We evaluated the safety of stopping breastfeeding at different ages for mortality of uninfected children born to HIV-infected mothers.
During a trial of early weaning, 958 HIV-infected mothers and their infants were recruited and followed from birth to 24 months in Lusaka, Zambia. Half of the cohort was randomized to wean abruptly at 4 months and the other half to continue breastfeeding. We examined associations between uninfected child mortality and actual breastfeeding duration investigating possible confounding and effect modification.
The mortality rate among 749 uninfected children was 9.4% by 12 months and 13.6% by 24 months. Weaning during the interval encouraged by the protocol (4-5 months) was associated with a 2.03-fold increased risk of mortality (95% CI: 1.13 - 3.65), weaning 6-11 months a 3.54-fold increase (95% CI: 1.68 - 7.46) and 12-18 months a 4.22-fold increase (95% CI: 1.59 - 11.24). Significant effect modification was detected such that risks associated with weaning were stronger among infants born to mothers with higher CD4 counts (>350 cells/mL).
Shortening the normal duration of breastfeeding for uninfected children born to HIV-infected mothers living in low resource settings is associated with significant increases mortality extending into the second year of life. Intensive nutritional and counseling interventions reduce, but do not eliminate, this excess mortality.
PMCID: PMC2805776  PMID: 20047479

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