Lynda Stranix-Chibanda

Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trial.

BACKGROUND Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally. We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months. METHODS In our phase 3, randomised, double-blind, placebo-controlled HPTN 046 trial, we assessed the incremental benefit of extension of once-daily infant nevirapine from age 6 weeks to 6 months. We enrolled breastfeeding infants born to mothers with HIV-1 in four African countries within 7 days of birth. Following receipt of nevirapine from birth to 6 weeks, infants without HIV infection were randomly allocated (by use of a computer-generated permuted block algorithm with random block sizes and stratified by site and maternal antiretroviral treatment status) to receive extended nevirapine prophylaxis or placebo until 6 months or until breastfeeding cessation, whichever came first. The primary efficacy endpoint was HIV-1 infection in infants at 6 months and safety endpoints were adverse reactions in both groups. We used Kaplan-Meier analyses to compare differences in the primary outcome between groups. This study is registered with ClinicalTrials.gov, number NCT00074412. FINDINGS Between June 19, 2008, and March 12, 2010, we randomly allocated 1527 infants (762 nevirapine and 765 placebo); five of whom had HIV-1 infection at randomisation and were excluded from the primary analyses. In Kaplan-Meier analysis, 1·1% (95% CI 0·3-1·8) of infants who received extended nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2·4% (1·3-3·6) of controls (difference 1·3%, 95% CI 0-2·6), equating to a 54% reduction in transmission (p=0·049). However, mortality (1·2% for nevirapine vs 1·1% for placebo; p=0·81) and combined HIV infection and mortality rates (2·3%vs 3·2%; p=0·27) did not differ between groups at 6 months. 125 (16%) of 758 infants given extended nevirapine and 116 (15%) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups. INTERPRETATION Nevirapine prophylaxis can safely be used to provide protection from mother-to-child transmission of HIV-1 via breastfeeding for infants up to 6 months of age. FUNDING US National Institutes of Health.

Validation of the Edinburgh Postnatal Depression Scale among women in a high HIV prevalence area in urban Zimbabwe

Despite the significant burden of common mental disorders (CMD) among women in sub Saharan Africa, data on postnatal depression (PND) is very limited, especially in settings with a high HIV prevalence. The Edinburgh Postnatal Depression Scale (EPDS), a widely used screening test for PND has been validated in many countries, but not in Zimbabwe. We assessed the validity of the EPDS scale among postpartum women compared with Diagnostic Manual of Mental Disorders (DSM-IV) criteria for major depression. Six trained community counselors administered the Shona version of the EPDS to a random sample of 210 postpartum HIV-infected and uninfected women attending two primary care clinics in Chitungwiza. All women were subsequently subjected to mental status examination using DSM IV criteria for major depression by 2 psychiatrists, who were blinded to the subject’s EPDS scores. Data were analyzed using receiver operating characteristic (ROC) curve analysis. Of the 210 postpartum mothers enrolled, 64 (33%) met DSM IV criteria for depression. Using a cut-off score of 11/12 on the Shona version of the EPDS for depression, the sensitivity was 88%, and specificity was 87%, with a positive predictive value of 74%, a negative predictive value of 94%, and an area under the curve of 0.82. Cronbachs alpha coefficient for the whole scale was 0.87. Conclusion: The Shona version of the EPDS is a reliable and valid tool to screen for PND among HIV-infected and un-infected women in Zimbabwe. Screening for PND should be integrated into routine antenatal and postnatal care in areas with high HIV prevalence.

The feasibility of preventing mother-to-child transmission of HIV using peer counselors in Zimbabwe.

BackgroundPrevention of mother-to-child transmission of HIV (PMTCT) is a major public health challenge in Zimbabwe.MethodsUsing trained peer counselors, a nevirapine (NVP)-based PMTCT program was implemented as part of routine care in urban antenatal clinics.ResultsBetween October 2002 and December 2004, a total of 19,279 women presented for antenatal care. Of these, 18,817 (98%) underwent pre-test counseling; 10,513 (56%) accepted HIV testing, of whom 1986 (19%) were HIV-infected. Overall, 9696 (92%) of women collected results and received individual post-test counseling. Only 288 men opted for HIV testing. Of the 1807 HIV-infected women who received posttest counseling, 1387 (77%) collected NVP tablet and 727 (40%) delivered at the clinics. Of the 1986 HIV-infected women, 691 (35%) received NVPsd at onset of labor, and 615 (31%) infants received NVPsd. Of the 727 HIV-infected women who delivered in the clinics, only 396 women returned to the clinic with their infants for the 6-week follow-up visit; of these mothers, 258 (59%) joined support groups and 234 (53%) opted for contraception. By the end of the study period, 209 (53%) of mother-infant pairs (n = 396) came to the clinic for at least 3 follow-up visits.ConclusionDespite considerable challenges and limited resources, it was feasible to implement a PMTCT program using peer counselors in urban clinics in Zimbabwe.

Factors associated with access to HIV care and treatment in a prevention of mother to child transmission programme in urban Zimbabwe

BackgroundThis cross-sectional study assessed factors affecting access to antiretroviral therapy (ART) among HIV-positive women from the prevention of mother to child transmission HIV programme in Chitungwiza, Zimbabwe.MethodsData were collected between June and August 2008. HIV-positive women attending antenatal clinics who had been referred to the national ART programme from January 2006 until December 2007 were surveyed. The questionnaire collected socio-demographic data, treatment-seeking behaviours, and positive or negative factors that affect access to HIV care and treatment.ResultsOf the 147 HIV-positive women interviewed, 95 (65%) had registered with the ART programme. However, documentation of the referral was noted in only 23 (16%) of cases. Of the 95 registered women, 35 (37%) were receiving ART; 17 (18%) had not undergone CD4 testing. Multivariate analysis revealed that participants who understood the referral process were three times more likely to access HIV care and treatment (OR = 3.21, 95% CI 1.89-11.65) and participants enrolled in an HIV support group were twice as likely to access care and treatment (OR = 2.34, 95% CI 1.13-4.88). Those living with a male partner were 60% less likely to access care and treatment (OR = 0.40, 95% CI 0.16-0.99). Participants who accessed HIV care and treatment faced several challenges, including long waiting times (46%), unreliable access to laboratory testing (35%) and high transport costs (12%). Of the 147 clients surveyed, 52 (35%) women did not access HIV care and treatment. Barriers included perceived long queues (50%), competing life priorities, such as seeking food or shelter (33%) and inadequate referral information (15%).ConclusionsDespite many challenges, the majority of participants accessed HIV care. Development of referral tools and decentralization of CD4 testing to clinics will improve access to ART. Psychosocial support can be a successful entry point to encourage client referral to care and treatment programmes.

Postnatal depression by HIV status among women in Zimbabwe.

BACKGROUND Postnatal depression (PND) is a serious public health problem in resource-limited countries. Research is limited on PND affecting HIV-infected women in sub-Saharan Africa. Zimbabwe has one of the highest antenatal HIV infection rates in the world. We determined the prevalence and risk factors of PND among women attending urban primary care clinics in Zimbabwe. METHODS Using trained peer counselors, a simple random sample of postpartum women (n = 210) attending the 6-week postnatal visit at two urban primary care clinics were screened for PND using the Shona version of the Edinburgh Postnatal Depression Scale (EPDS). All women were subsequently subjected to mental status examination using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for major depression by two psychiatrists who had no knowledge of the EPDS test results. RESULTS Of the 210 mothers (31 HIV positive, 148 HIV negative, 31 unknown status) enrolled during the postpartum period, 64 (33%) met DSM-IV criteria for depression. The HIV prevalence was 14.8%. Of the 31 HIV-infected mothers, 17(54%) met DSM-IV criteria for depression. Univariate analysis showed that multiparity (prevalent odds ratio [OR] 2.22, 95% confidence intervals [CI] 1.15-4.31), both parents deceased (OR 2.35, 95% CI 1.01-5.45), and having experienced a recent adverse life event (OR 8.34, CI 3.77-19.07) were significantly associated with PND. Multivariate analysis showed that PND was significantly associated with adverse life event (OR 7.04, 95% CI 3.15-15.76), being unemployed (OR 3.12, 95% CI 1.23-7.88), and multiparity (OR 2.50, 95% CI 1.00-6.24). CONCLUSIONS Our data indicate a high burden of PND among women in Zimbabwe. It is feasible to screen for PND in primary care clinics using peer counselors. Screening for PND and access to mental health interventions should be part of routine antenatal care for all women in Zimbabwe.

Group Problem-Solving Therapy for Postnatal Depression among HIV-Positive and HIV-Negative Mothers in Zimbabwe:

Postnatal depression (PND) is a major problem in low- and middle-income countries (LMICs). A total of 210 postpartum mothers attending primary care urban clinics were screened for PND at 6 weeks postpartum using the Edinburgh Postnatal Depression Scale (EPDS) and Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition; DSM-IV) criteria for major depression. The HIV prevalence was 14.8%. Of the 210 enrolled postpartum mothers, 64 (33%) met DSM IV criteria for depression. Using trained peer counselors, mothers with PND (n = 58) were randomly assigned to either group problem-solving therapy (PST, n = 30) or amitriptyline (n = 28). Of the 58 mothers with PND, 49 (85%) completed 6 weeks of group PST (n = 27) or pharmacotherapy (n = 22). At baseline, the mean EPDS score for participants randomized to group PST was 17.3 (standard deviation [SD] 3.7), while the group randomized to amitriptyline had a mean EPDS score of 17.9 (SD 3.9; P = .581). At 6 weeks postintervention, the drop in mean EPDS score was greater in the PST group (8.22, SD 3.6) compared to the amitriptyline group (10.7, SD 2.7; P = .0097). Group PST using peer counselors is feasible, acceptable, and more effective compared to pharmacotherapy in the treatment of PND. Group PST could be integrated into maternal and child health clinics and preventing mother-to-child transmission of HIV programs in LMICs.

Screening for Psychological Morbidity in HIV-Infected and HIV-Uninfected Pregnant Women Using Community Counselors in Zimbabwe

Objective: To examine the prevalence of psychological morbidity in HIV-infected and uninfected pregnant women seeking antenatal care in Zimbabwe. Methods: Pregnant women were screened for psychological morbidity at the initial antenatal care visit using the 14-item Shona Symptom Questionnaire (SSQ) before voluntary HIV counseling and testing (VCT). The primary outcome measure was “cases,” as determined by a SSQ score of= 8. Demographic characteristics and HIV status were compared between cases and noncases to determine the risk factors for psychological morbidity. Results: Of the 437 participants, psychological morbidity was detected in 73 (17%) women before undergoing VCT. Risk factors for psychological morbidity included having a spouse older than 35 years of age. HIV infection by itself was not a risk factor for psychological morbidity for women. Conclusions: There is a high burden of psychological morbidity among pregnant women in Zimbabwe. Mental health services should be integrated into antenatal care to improve psychological health for all women in Zimbabwe.

Immunologic response to oral polio vaccine in human immunodeficiency virus-infected and uninfected Zimbabwean children.

Background: Poliovirus eradication is dependent on maintaining adequate community-wide levels of serologic protection. Many African countries with conditions that favor continued wild poliovirus propagation also have a high prevalence of pediatric human immunodeficiency virus (HIV) infection. Data are limited regarding the degree of serologic immunity conferred on HIV-infected children after immunization with oral polio vaccine (OPV). Methods: This was a cross-sectional study correlating HIV infection and neutralizing antibodies against poliovirus serotypes 1, 2, and 3 in 95 Zimbabwean children 2 months to 2 years of age, born to HIV-infected mothers, who received OPV according to the national schedule. Results: HIV-infected children had significantly lower rates of seroconversion to all 3 poliovirus serotypes than HIV-uninfected children (60%, 67%, and 47% vs. 96%, 100%, and 82%, P = 0.001, 0.0003, and 0.015 for serotypes 1, 2, and 3 in HIV-infected and uninfected children, respectively, after ≥3 OPV doses). Among poliovirus seroconverters, HIV-infected children also had significantly lower geometric mean titers against serotypes 1 and 2 than HIV-uninfected children (geometric mean titers: 198 and 317 vs. 1193 and 1056, P = 0.032 and 0.050, for serotypes 1 and 2, respectively, after ≥3 OPV doses). In addition, HIV-infected children had significantly higher levels of total IgG and significantly lower CD4% and mean weight than HIV-uninfected children. Of note, none of the HIV-infected children were receiving antiretroviral therapy, and 71% had a CD4% indicating severe immunodeficiency. Conclusions: Pediatric HIV infection is associated with a poor serologic response to OPV, which could pose an obstacle to global polio eradication.

Efficacy and safety of an extended nevirapine regimen in infants of breastfeeding mothers with HIV-1 infection for prevention of HIV-1 transmission (HPTN 046): 18-month results of a randomized, double-blind, placebo-controlled trial.

Background:HPTN 046 compared the efficacy and safety of infant nevirapine (NVP) among HIV-exposed breastfed infants randomized at 6 weeks to 6 months to t NVP or placebo to prevent postnatal infection: we report final 18-month outcomes. Methods:Randomized, placebo-controlled trial in 4 African countries. Infant diagnostic HIV testing was performed regularly from birth through 18 months. Kaplan–Meier analysis was used to assess 18-month cumulative infant HIV infection, HIV infection/or death, and mortality rates. Results:Between 6 weeks and 6 months, postnatal HIV infection rates were significantly lower among infants receiving daily NVP from 6 weeks to 6 months 1.1% [95% confidence interval (CI): 0.2% to 1.8%], compared with placebo 2.4% (95% CI: 1.3% to 2.6%), P = 0.049, but not significantly lower thereafter. Eighteen-month postnatal infection rates were low: 2.2% (95% CI: 1.1% to 3.3%) versus 3.1% (95% CI: 1.9% to 4.4%), respectively, P = 0.28. Mortality and HIV infection/death did not differ between arms at any age. Infants of women receiving antiretroviral therapy (ART) for their own health had the lowest 18-month postnatal infection rates (0.5%, 95% CI: 0.0% to 1.1%). However, HIV infection/death rates at 18 months were not significantly different for infants of mothers on ART (3.7%, 95% CI: 1.9% to 5.5%), and infants of mothers with CD4 counts of ≥350 cells per cubic millimeter not receiving ART (4.8%, 95% CI: 2.7% to 6.8%; P = 0.46). There were no differences in adverse events between study arms. Conclusions:This trial demonstrated early but not late differences in postnatal HIV transmission among infants randomized at age 6 weeks to extended NVP or placebo, underscoring the importance of continued prophylaxis throughout breastfeeding.

Factors associated with repeat pregnancy among women in an area of high HIV prevalence in Zimbabwe.

BACKGROUND This study examined predictors of repeat pregnancy among women from the Prevention of Mother-to-Child Transmission of HIV (PMTCT) program in Zimbabwe. METHODS The study was conducted at urban antenatal clinics in Chitungwiza, a high HIV prevalence urban town on the outskirts of Harare, Zimbabwe. Using a cross-sectional design, 79 HIV-positive and 80 HIV-negative women who had participated in a PMTCT program in their index pregnancy were interviewed in Shona using a standardized questionnaire 24 months after delivery of their index pregnancy. Logistic regression was used to determine whether a relationship exists between repeat pregnancy and HIV status, socioeconomic status, age, Fertility Attitude Score, and previous pregnancy outcomes. RESULTS In multivariate analysis, factors associated with an increased likelihood of repeat pregnancy were death of a child (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.25-12.52; p = .0019), miscarriage (OR, 3.4; 95% CI, 1.23-9.34; p = .019), and each additional child (OR, 4.6; 95% CI, 1.89-11.52; p = .001). Decreased likelihood of repeat pregnancy was associated with decreased rank order of living conditions (OR, -0.75; 95% CI, 0.55-0.95; p = .021), each additional year of age (OR, -0.86; 95% CI, 0.77-0.97; p = .012), and higher Fertility Attitude Score (OR, -0.76; 95% CI, 0.64-0.91; p = .002). CONCLUSION HIV status alone was not significant as a predictor of repeat pregnancy. Womens childbearing intentions are not influenced by the risk of mother-to-child transmission of HIV (MTCT) in this population. Future research is needed to address the cultural attitudes and sexual practices of HIV-positive women in order to minimize the threat of MTCT.