Chipepo Kankasa

Effects of early, abrupt weaning on HIV-free survival of children in Zambia.

BACKGROUND In low-resource settings, many programs recommend that women who are infected with the human immunodeficiency virus (HIV) stop breast-feeding early. We conducted a randomized trial to evaluate whether abrupt weaning at 4 months as compared with the standard practice has a net benefit for HIV-free survival of children. METHODS We enrolled 958 HIV-infected women and their infants in Lusaka, Zambia. All the women planned to breast-feed exclusively to 4 months; 481 were randomly assigned to a counseling program that encouraged abrupt weaning at 4 months, and 477 to a program that encouraged continued breast-feeding for as long as the women chose. The primary outcome was either HIV infection or death of the child by 24 months. RESULTS In the intervention group, 69.0% of the mothers stopped breast-feeding at 5 months or earlier; 68.8% of these women reported the completion of weaning in less than 2 days. In the control group, the median duration of breast-feeding was 16 months. In the overall cohort, there was no significant difference between the groups in the rate of HIV-free survival among the children; 68.4% and 64.0% survived to 24 months without HIV infection in the intervention and control groups, respectively (P=0.13). Among infants who were still being breast-fed and were not infected with HIV at 4 months, there was no significant difference between the groups in HIV-free survival at 24 months (83.9% and 80.7% in the intervention and control groups, respectively; P=0.27). Children who were infected with HIV by 4 months had a higher mortality by 24 months if they had been assigned to the intervention group than if they had been assigned to the control group (73.6% vs. 54.8%, P=0.007). CONCLUSIONS Early, abrupt cessation of breast-feeding by HIV-infected women in a low-resource setting, such as Lusaka, Zambia, does not improve the rate of HIV-free survival among children born to HIV-infected mothers and is harmful to HIV-infected infants.(ClinicalTrials.gov number, NCT00310726.)

Exclusive breastfeeding promotion by peer counsellors in sub-Saharan Africa (PROMISE-EBF): a cluster-randomised trial

BACKGROUND Exclusive breastfeeding (EBF) is reported to be a life-saving intervention in low-income settings. The effect of breastfeeding counselling by peer counsellors was assessed in Africa. METHODS 24 communities in Burkina Faso, 24 in Uganda, and 34 in South Africa were assigned in a 1:1 ratio, by use of a computer-generated randomisation sequence, to the control or intervention clusters. In the intervention group, we scheduled one antenatal breastfeeding peer counselling visit and four post-delivery visits by trained peers. The data gathering team were masked to the intervention allocation. The primary outcomes were prevalance of EBF and diarrhoea reported by mothers for infants aged 12 weeks and 24 weeks. Country-specific prevalence ratios were adjusted for cluster effects and sites. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00397150. FINDINGS 2579 mother-infant pairs were assigned to the intervention or control clusters in Burkina Faso (n=392 and n=402, respectively), Uganda (n=396 and n=369, respectively), and South Africa (n=535 and 485, respectively). The EBF prevalences based on 24-h recall at 12 weeks in the intervention and control clusters were 310 (79%) of 392 and 139 (35%) of 402, respectively, in Burkina Faso (prevalence ratio 2·29, 95% CI 1·33-3·92); 323 (82%) of 396 and 161 (44%) of 369, respectively, in Uganda (1·89, 1·70-2·11); and 56 (10%) of 535 and 30 (6%) of 485, respectively, in South Africa (1·72, 1·12-2·63). The EBF prevalences based on 7-day recall in the intervention and control clusters were 300 (77%) and 94 (23%), respectively, in Burkina Faso (3·27, 2·13-5·03); 305 (77%) and 125 (34%), respectively, in Uganda (2·30, 2·00-2·65); and 41 (8%) and 19 (4%), respectively, in South Africa (1·98, 1·30-3·02). At 24 weeks, the prevalences based on 24-h recall were 286 (73%) in the intervention cluster and 88 (22%) in the control cluster in Burkina Faso (3·33, 1·74-6·38); 232 (59%) and 57 (15%), respectively, in Uganda (3·83, 2·97-4·95); and 12 (2%) and two (<1%), respectively, in South Africa (5·70, 1·33-24·26). The prevalences based on 7-day recall were 279 (71%) in the intervention cluster and 38 (9%) in the control cluster in Burkina Faso (7·53, 4·42-12·82); 203 (51%) and 41 (11%), respectively, in Uganda (4·66, 3·35-6·49); and ten (2%) and one (<1%), respectively, in South Africa (9·83, 1·40-69·14). Diarrhoea prevalence at age 12 weeks in the intervention and control clusters was 20 (5%) and 36 (9%), respectively, in Burkina Faso (0·57, 0·27-1·22); 39 (10%) and 32 (9%), respectively, in Uganda (1·13, 0·81-1·59); and 45 (8%) and 33 (7%), respectively, in South Africa (1·16, 0·78-1·75). The prevalence at age 24 weeks in the intervention and control clusters was 26 (7%) and 32 (8%), respectively, in Burkina Faso (0·83, 0·45-1·54); 52 (13%) and 59 (16%), respectively, in Uganda (0·82, 0·58-1·15); and 54 (10%) and 33 (7%), respectively, in South Africa (1·31, 0·89-1·93). INTERPRETATION Low-intensity individual breastfeeding peer counselling is achievable and, although it does not affect the diarrhoea prevalence, can be used to effectively increase EBF prevalence in many sub-Saharan African settings. FUNDING European Union Sixth Framework International Cooperation-Developing Countries, Research Council of Norway, Swedish International Development Cooperation Agency, Norwegian Programme for Development, Research and Education, South African National Research Foundation, and Rockefeller Brothers Foundation.

Barriers to acceptance and adherence of antiretroviral therapy in urban Zambian women: a qualitative study

Abstract Sub-Saharan Africa contains over 60% of the worlds HIV infections and Zambia is among the most severely affected countries in the region. As antiretroviral programs have been rapidly expanding, the long-term success of these programs depends on a good understanding of the behavioral determinants of acceptance and adherence to antiretroviral therapy (ART). The study used qualitative methods to gain local insight into potentially important factors affecting HIV-infected womens decision to accept or continue with ART. Some of the barriers identified by this study are consistent with factors cited in the existing adherence literature from both developed and developing nations such as side effects, hunger and stigma; other factors have not been previously reported. One major theme was unfamiliarity with the implications of having a chronic, potentially deadly disease. Other emerging themes from this study include the complicated effect of ART on interpersonal relationship, particularly between husbands and wives, the presence of depression and hopelessness, and lack of accurate information. The results suggest that the reasons for non-uptake of treatment include issues related to local cultural frameworks (e.g., illness ideology), mental and behavioral health (e.g., depression and/or interpersonal challenges), stigma, and motivating factors (e.g., values of church or marriage) of different cultures that affect the ability and willingness to take life-saving medicine for a long period of time. Qualitative studies are critical to better understand why ART eligible individuals are choosing not to initiate or continue treatment to achieve needed adherence levels.

Women in couples antenatal HIV counseling and testing are not more likely to report adverse social events

Background: Couple counseling has been promoted as a strategy to improve uptake of interventions to prevent mother-to-child HIV transmission (pMTCT) and to minimize adverse social outcomes associated with disclosure of HIV status. Objectives: We tested whether women counseled antenatally as part of a couple were more likely to accept HIV testing and nevirapine in a pMTCT program, and whether they would be less likely to experience later adverse social events than women counseled alone. Methods: A pMTCT program that included active community education and outreach to encourage couple counseling and testing was implemented in two antenatal clinics in Lusaka, Zambia. A subset of HIV-positive women was asked to report their experience of adverse social events 6 months after delivery. Couple-counseled women were compared with individual-counseled women stratified by whether or not they had disclosed their HIV status to their partners. Results: Nine percent (868) of 9409 women counseled antenatally were counseled with their husband. Couple-counseled women were more likely to accept HIV testing (96%) than women counseled alone (79%); however uptake of nevirapine was not improved. Six months after delivery, 28% of 324 HIV-positive women reported at least one adverse social event (including physical violence, verbal abuse, divorce or separation). There were no significant differences in reported adverse social events between couple- and individual-counseled women. Conclusions: Couple counseling did not increase the risk of adverse social events associated with HIV disclosure. Support services and interventions to improve social situations for people living with HIV need to be further evaluated.

Does Severity of HIV Disease in HIV-Infected Mothers Affect Mortality and Morbidity among Their Uninfected Infants?

BACKGROUND Rates of perinatal human immunodeficiency virus (HIV) transmission are higher among HIV-infected mothers with more advanced disease, but effects of maternal disease on HIV-uninfected offspring are unclear. We investigated the hypothesis that the severity of HIV disease and immune dysfunction among mothers is associated with increased morbidity and mortality among their uninfected infants. METHODS In a birth cohort of 620 HIV-uninfected infants born to HIV-infected mothers in Lusaka, Zambia, we investigated associations between markers of more advanced maternal HIV disease and child mortality, hospital admissions, and infant weight through 4 months of age. RESULTS Mortality in the cohort of uninfected infants was 4.6% (95% confidence interval [CI], 2.8-6.3) through 4 months of age. Infants of mothers with CD4+ T cell counts of <350 cells/microL were more likely to die (hazard ratio [HR], 2.87; 95% CI, 1.03-8.03) and were more likely to be hospitalized (HR, 2.28; 95% CI, 1.17-4.45), after adjusting for other factors, including maternal death and low birth weight. The most common cause of infant death and hospitalization was pneumonia and/or sepsis. A maternal viral load of >100,000 copies/mL was associated with significantly lower child weight through 4 months of age. CONCLUSION Children born to HIV-infected mothers with advanced disease who escaped perinatal or early breastfeeding-related HIV infection are nonetheless at high risk of mortality and morbidity during the first few months of life. HIV-related immunosuppression appears to have adverse consequences for the health of infants, in addition to risks of vertical transmission.

Effectiveness of a city-wide program to prevent mother-to-child HIV transmission in Lusaka, Zambia

Objective:To determine the population effectiveness of a city-wide perinatal HIV prevention program. Design:An anonymous surveillance of newborn cord blood for HIV serology and nevirapine (NVP). Methods:All 10 public-sector delivery centers in Lusaka, Zambia participated. All mother–infant pairs delivering during the 12-week surveillance period at the participating centers and who received antenatal care at a public-sector facility in Lusaka were included in the study. The main outcome measure was population NVP coverage, defined as the proportion of HIV-infected women and HIV-exposed infants in the population that ingested NVP. Results:Of 8787 women in the surveillance population, 7204 (82%) had been offered antenatal HIV testing, of which 5149 (71%) had accepted, and of which 5129 (99%) had received a result. Overall, 2257 of 8787 (26%) were cord seropositive. Of the 1246 (55%) cord blood seropositive women who received an antenatal HIV test result, 1112 (89%) received a positive result; the other 134 comprise seroconverters and clerical errors. Only 751 of 1112 (68%) women who received a positive antenatal test result and a NVP tablet for ingestion at labor onset had NVP detected in the cord blood (i.e., maternal non-adherence rate was 32%). A total of 675 infants born to 751 adherent mothers (90%) received NVP before discharge. Thus, only 675 of 2257 (30%) seropositive mother–infant pairs in the surveillance population received both a maternal and infant dose of NVP. Conclusions:Successful perinatal HIV prevention requires each mother–infant pair to negotiate a cascade of events that begins with offering HIV testing and continues through adherence to the prescribed regimen. This novel surveillance demonstrates that failures occur at each step, resulting in reduced coverage and diminished program effectiveness.

High uptake of exclusive breastfeeding and reduced early post-natal HIV transmission.

Background Empirical data showing the clear benefits of exclusive breastfeeding (EBF) for HIV prevention are needed to encourage implementation of lactation support programs for HIV-infected women in low resource settings among whom replacement feeding is unsafe. We conducted a prospective, observational study in Lusaka, Zambia, to test the hypothesis that EBF is associated with a lower risk of postnatal HIV transmission than non-EBF. Methods and Results As part of a randomized trial of early weaning, 958 HIV-infected women and their infants were recruited and all were encouraged to breastfeed exclusively to 4 months. Single-dose nevirapine was provided to prevent transmission. Regular samples were collected from infants to 24 months of age and tested by PCR. Detailed measurements of actual feeding behaviors were collected to examine, in an observational analysis, associations between feeding practices and postnatal HIV transmission. Uptake of EBF was high with 84% of women reporting only EBF cumulatively to 4 months. Post-natal HIV transmission before 4 months was significantly lower (p = 0.004) among EBF (0.040 95% CI: 0.024–0.055) than non-EBF infants (0.102 95% CI: 0.047–0.157); time-dependent Relative Hazard (RH) of transmission due to non-EBF = 3.48 (95% CI: 1.71–7.08). There were no significant differences in the severity of disease between EBF and non-EBF mothers and the association remained significant (RH = 2.68 95% CI: 1.28–5.62) after adjusting for maternal CD4 count, plasma viral load, syphilis screening results and low birth weight. Conclusions Non-EBF more than doubles the risk of early postnatal HIV transmission. Programs to support EBF should be expanded universally in low resource settings. EBF is an affordable, feasible, acceptable, safe and sustainable practice that also reduces HIV transmission providing HIV-infected women with a means to protect their childrens lives. Trial Registration ClinicalTrials.gov NCT00310726

Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trial

BACKGROUND Intrapartum and neonatal single-dose nevirapine are essential components of perinatal HIV prevention in resource-constrained settings, but can induce resistance to other non-nucleoside reverse transcriptase inhibitor drugs. We aimed to investigate whether this complication would be reduced with a single peripartum intervention of tenofovir and emtricitabine. METHODS We randomly assigned 400 HIV-infected pregnant women who sought care at two public-sector primary health facilities in Lusaka, Zambia. One was excluded, 200 were assigned to receive a single oral dose of 300 mg tenofovir disoproxil fumarate with 200 mg emtricitabine under direct observation, and 199 to receive no study drug. Short-course zidovudine and intrapartum nevirapine were offered to all HIV-infected women, according to the local standard of care. Women who met national criteria for antiretroviral therapy were referred for care and not enrolled. Our primary study outcome was resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery. We used standard population sequencing to determine HIV genotypes. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00204308. FINDINGS Of the 200 women who were randomly assigned to the intervention, 14 were lost to follow-up or withdrew from the study, two did not take study drug according to protocol, and one specimen was lost; 23 of 199 controls were lost to follow-up or withdrew from the study, and three specimens were lost. Women given the intervention were 53% less likely than controls to have a mutation that conferred resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery (20/173 [12%] vs 41/166 [25%]; risk ratio [RR] 0.47, 95% CI 0.29-0.76). We noted postpartum anaemia, the most common serious adverse event in mothers, in four women in each group. 20 of 198 (10%) infants in the intervention group and 23 of 199 (12%) controls had a serious adverse event, mostly due to septicaemia (n=22) or pneumonia (n=8); these events did not differ between groups, and none were judged to be caused by the study intervention. INTERPRETATION A single dose of tenofovir and emtricitabine at delivery reduced resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery by half; therefore this treatment should be considered as an adjuvant to intrapartum nevirapine.

Growth faltering due to breastfeeding cessation in uninfected children born to HIV-infected mothers in Zambia

BACKGROUND The effect of breastfeeding on growth in HIV-exposed infants is not well described. OBJECTIVE The objective was to evaluate the effect of early breastfeeding cessation on growth. DESIGN In a trial conducted in Lusaka, Zambia, HIV-infected mothers were randomly assigned to exclusive breastfeeding for 4 mo followed by rapid weaning to replacement foods or exclusive breastfeeding for 6 mo followed by introduction of complementary foods and continued breastfeeding for a duration of the mothers choice. Weight-for-age z score (WAZ), length-for-age z score (LAZ), and weight-for-length z score (WLZ) and the self-reported breastfeeding practices of 593 HIV-uninfected singletons were analyzed. Generalized estimating equations were used to adjust for confounders. RESULTS WAZ scores declined precipitously between 4.5 and 15 mo. The decline was slower in the breastfed infants. At 9, 12, and 15 mo, mean WAZs were, respectively, -0.74, -0.92, and -1.06 in infants who were reportedly breastfed and were -1.07, -1.20, and -1.31 in the weaned infants (P = 0.003, 0.007, and 0.02, respectively). No differences were observed past 15 mo. Breastfeeding practice was not associated with LAZ, which declined from -0.98 to -2.24 from 1 to 24 mo. After adjustment for birth weight, maternal viral load, body mass index, education, season, and marital and socioeconomic status, not breastfeeding was associated with a 0.28 decline in WAZ between 4.5 and 15 mo (P < 0.0001). During the rainy season, not breastfeeding was associated with a larger WAZ decline (0.33) than during the dry season (0.22; P for interaction = 0.02). CONCLUSIONS Early growth is compromised in uninfected children born to HIV-infected Zambian mothers. Continued breastfeeding partially mitigates this effect through 15 mo. Nutritional interventions to complement breastfeeding after 6 mo are urgently needed. This trial was registered at clinicaltrials.gov as NCT00310726.

Elevations in Mortality Associated with Weaning Persist into the Second Year of Life among Uninfected Children Born to HIV-Infected Mothers

BACKGROUND Early weaning has been recommended to reduce postnatal human immunodeficiency virus (HIV) transmission. We evaluated the safety of stopping breast-feeding at different ages for mortality of uninfected children born to HIV-infected mothers. METHODS During a trial of early weaning, 958 HIV-infected mothers and their infants were recruited and followed up from birth to 24 months postpartum in Lusaka, Zambia. One-half of the cohort was randomized to wean abruptly at 4 months, and the other half of the cohort was randomized to continue breast-feeding. We examined associations between uninfected child mortality and actual breast-feeding duration and investigated possible confounding and effect modification. RESULTS The mortality rate among 749 uninfected children was 9.4% by 12 months of age and 13.6% by 24 months of age. Weaning during the interval encouraged by the protocol (4-5 months of age) was associated with a 2.03-fold increased risk of mortality (95% confidence interval [CI], 1.13-3.65), weaning at 6-11 months of age was associated with a 3.54-fold increase (95% CI, 1.68-7.46), and weaning at 12-18 months of age was associated with 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(+) cell counts (>350 cells/microL). CONCLUSION Shortening the normal duration of breast-feeding for uninfected children born to HIV-infected mothers living in low-resource settings is associated with significant increases in mortality extending into the second year of life. Intensive nutritional and counseling interventions reduce but do not eliminate this excess mortality.