Publications (16)100.1 Total impact
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Article: Measuring Coverage in MNCH: Population HIV-Free Survival among Children under Two Years of Age in Four African Countries.
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ABSTRACT: Population-based evaluations of programs for prevention of mother-to-child HIV transmission (PMTCT) are scarce. We measured PMTCT service coverage, regimen use, and HIV-free survival among children ≤24 mo of age in Cameroon, Côte D'Ivoire, South Africa, and Zambia. We randomly sampled households in 26 communities and offered participation if a child had been born to a woman living there during the prior 24 mo. We tested consenting mothers with rapid HIV antibody tests and tested the children of seropositive mothers with HIV DNA PCR or rapid antibody tests. Our primary outcome was 24-mo HIV-free survival, estimated with survival analysis. In an individual-level analysis, we evaluated the effectiveness of various PMTCT regimens. In a community-level analysis, we evaluated the relationship between HIV-free survival and community PMTCT coverage (the proportion of HIV-exposed infants in each community that received any PMTCT intervention during gestation or breastfeeding). We also compared our community coverage results to those of a contemporaneous study conducted in the facilities serving each sampled community. Of 7,985 surveyed children under 2 y of age, 1,014 (12.7%) were HIV-exposed. Of these, 110 (10.9%) were HIV-infected, 851 (83.9%) were HIV-uninfected, and 53 (5.2%) were dead. HIV-free survival at 24 mo of age among all HIV-exposed children was 79.7% (95% CI: 76.4, 82.6) overall, with the following country-level estimates: Cameroon (72.6%; 95% CI: 62.3, 80.5), South Africa (77.7%; 95% CI: 72.5, 82.1), Zambia (83.1%; 95% CI: 78.4, 86.8), and Côte D'Ivoire (84.4%; 95% CI: 70.0, 92.2). In adjusted analyses, the risk of death or HIV infection was non-significantly lower in children whose mothers received a more complex regimen of either two or three antiretroviral drugs compared to those receiving no prophylaxis (adjusted hazard ratio: 0.60; 95% CI: 0.34, 1.06). Risk of death was not different for children whose mothers received a more complex regimen compared to those given single-dose nevirapine (adjusted hazard ratio: 0.88; 95% CI: 0.45, 1.72). Community PMTCT coverage was highest in Cameroon, where 75 of 114 HIV-exposed infants met criteria for coverage (66%; 95% CI: 56, 74), followed by Zambia (219 of 444, 49%; 95% CI: 45, 54), then South Africa (152 of 365, 42%; 95% CI: 37, 47), and then Côte D'Ivoire (3 of 53, 5.7%; 95% CI: 1.2, 16). In a cluster-level analysis, community PMTCT coverage was highly correlated with facility PMTCT coverage (Pearson's r = 0.85), and moderately correlated with 24-mo HIV-free survival (Pearson's r = 0.29). In 14 of 16 instances where both the facility and community samples were large enough for comparison, the facility-based coverage measure exceeded that observed in the community. HIV-free survival can be estimated with community surveys and should be incorporated into ongoing country monitoring. Facility-based coverage measures correlate with those derived from community sampling, but may overestimate population coverage. The more complex regimens recommended by the World Health Organization seem to have measurable public health benefit at the population level, but power was limited and additional field validation is needed. Please see later in the article for the Editors' Summary.PLoS Medicine 05/2013; 10(5):e1001424. · 16.27 Impact Factor -
Article: Non-virologic algorithms for predicting HIV infection among HIV-exposed infants under 12 weeks of age.
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ABSTRACT: BACKGROUND:: Early initiation of antiretroviral therapy (ART) has been shown to reduce mortality among perinatally HIV-infected infants, but availability of virologic testing remains limited in many settings. METHODS:: We collected cross-sectional data from mother-infant pairs in three primary care clinics in Lusaka, Zambia to develop predictive models for HIV infection among infants age <12 weeks. We evaluated algorithm performance for all possible combinations of selected parameters using an iterative approach. In primary analysis, we identified the model with the highest combined sensitivity and specificity. RESULTS:: Between July 2009 and May 2011, 822 eligible HIV-infected mothers and their HIV-exposed infants were enrolled; of these, 44 (5.4%) infants were diagnosed with HIV. We evaluated 382,155,260 different parameter combinations for predicting infant HIV infection. The algorithm with highest combined sensitivity and specificity required 5 of the following 7 parameter thresholds: infant CD8% > 22, infant CD4% ≤ 44, infant weight-for-age Z score ≤ 0, infant CD4 ≤ 1600 cells/µL, infant CD8 > 2200 cells/µL, ternal CD4 ≤ 600 cells/µL, and mother not currently on ART for HIV treatment. This combination had a sensitivity of 90.3%, specificity of 78.4%, positive predictive value (PPV) of 22.4%, negative predictive value (NPV) of 99.2%, and area under the curve (AUC) of 0.844. CONCLUSION:: Predicting HIV infection in HIV-exposed infants in this age group is difficult using clinical and immunologic parameters. Expansion of PCR capacity in resource-limited settings remains urgently needed.The Pediatric Infectious Disease Journal 08/2012; · 3.58 Impact Factor -
Article: Six-month hemoglobin concentration and its association with subsequent mortality among adults on antiretroviral therapy in Lusaka, Zambia.
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ABSTRACT: Little is known about changes in hemoglobin concentration early in the course of antiretroviral therapy and its subsequent relation to survival. We analyzed data for 40,410 HIV-infected adults on antiretroviral therapy in Lusaka, Zambia. Our main exposure of interest was 6-month hemoglobin, but we stratified our analysis by baseline hemoglobin to allow for potential effect modification. Patients with a 6-month hemoglobin <8.5 g/dL, regardless of baseline, had the highest hazard for death after 6 months (hazard ratio: 4.5; 95% confidence interval: 3.3 to 6.3). Future work should look to identify causes of anemia in settings such as ours and evaluate strategies for more timely diagnosis and treatment.JAIDS Journal of Acquired Immune Deficiency Syndromes 05/2012; 61(1):120-3. · 4.43 Impact Factor -
Article: Effectiveness of generic and proprietary first-line anti-retroviral regimens in a primary health care setting in Lusaka, Zambia: a cohort study.
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ABSTRACT: Although generic anti-retroviral drugs are in common use throughout the developing world, studies comparing their clinical effectiveness with that of proprietary formulations are lacking. We analysed observational data from a large cohort of adults on anti-retroviral therapy (ART) to assess potential differences between generic and proprietary zidovudine (ZDV) formulations in post-90-day mortality, 'programme failure' (a composite of death, follow-up losses and withdrawals) and other clinical outcomes. We accounted for drug exposure in three ways: an 'initial dispensation' approach that categorized patients according to the first prescription; 'time-varying' approach that attributed an outcome to the formulation taken at the time of event; and 'predominant exposure' approach that considered only those with >75% exposure to either brand or generic ZDV. Proprietary formulations were used as the reference group in all adjusted Cox proportional hazard regressions. Among 14 736 patients eligible for analysis, 7277 (49%) initiated a generic formulation of ZDV and 7459 (51%) initiated a proprietary formulation. When categorized according to initial dispensation, no difference in post-90-day mortality was observed between the two groups [adjusted hazard ratio (AHR): 0.93, 95% confidence interval (CI): 0.77-1.12]. Similar findings were noted when drug formulation was treated as a time-varying exposure (AHR: 1.15, 95% CI: 0.89-1.48) when analysis was limited to those with a predominant exposure to one formulation or the other (AHR: 0.59, 95% CI: 0.24-1.49). Results were consistent across all approaches when programme failure was considered as an outcome. No longitudinal differences were detected between formulations for CD4 response, weight change and haemoglobin concentration. Generic ZDV formulations were associated with slight decreases in single-drug substitution. In this large programmatic cohort of adults starting ZDV-based first-line therapy, clinical outcomes appeared similar among patients on generic or proprietary formulations. These findings support continued use of generic anti-retroviral drug formulations in resource-constrained settings.International Journal of Epidemiology 04/2012; 41(2):448-59. · 6.41 Impact Factor -
Article: Taking ART to Scale: Determinants of the Cost and Cost-Effectiveness of Antiretroviral Therapy in 45 Clinical Sites in Zambia.
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ABSTRACT: We estimated the unit costs and cost-effectiveness of a government ART program in 45 sites in Zambia supported by the Centre for Infectious Disease Research Zambia (CIDRZ). We estimated per person-year costs at the facility level, and support costs incurred above the facility level and used multiple regression to estimate variation in these costs. To estimate ART effectiveness, we compared mortality in this Zambian population to that of a cohort of rural Ugandan HIV patients receiving co-trimoxazole (CTX) prophylaxis. We used micro-costing techniques to estimate incremental unit costs, and calculated cost-effectiveness ratios with a computer model which projected results to 10 years. The program cost $69.7 million for 125,436 person-years of ART, or $556 per ART-year. Compared to CTX prophylaxis alone, the program averted 33.3 deaths or 244.5 disability adjusted life-years (DALYs) per 100 person-years of ART. In the base-case analysis, the net cost per DALY averted was $833 compared to CTX alone. More than two-thirds of the variation in average incremental total and on-site cost per patient-year of treatment is explained by eight determinants, including the complexity of the patient-case load, the degree of adherence among the patients, and institutional characteristics including, experience, scale, scope, setting and sector. The 45 sites exhibited substantial variation in unit costs and cost-effectiveness and are in the mid-range of cost-effectiveness when compared to other ART programs studied in southern Africa. Early treatment initiation, large scale, and hospital setting, are associated with statistically significantly lower costs, while others (rural location, private sector) are associated with shifting cost from on- to off-site. This study shows that ART programs can be significantly less costly or more cost-effective when they exploit economies of scale and scope, and initiate patients at higher CD4 counts.PLoS ONE 01/2012; 7(12):e51993. · 4.09 Impact Factor -
Article: Comparative outcomes of tenofovir-based and zidovudine-based antiretroviral therapy regimens in Lusaka, Zambia.
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ABSTRACT: Although tenofovir (TDF) is a common component of antiretroviral therapy (ART), recent evidence suggests inferior outcomes when it is combined with nevirapine (NVP). We compared outcomes among patients initiating TDF + emtricitabine or lamivudine (XTC) + NVP, TDF + XTC + efavirenz (EFV), zidovudine (ZDV) + lamuvidine (3TC) + NVP, and ZDV + 3TC + EFV. We categorized drug exposure by initial ART dispensation by a time-varying analysis that accounted for drug substitutions and by predominant exposure (>75% of drug dispensations) during an initial window period. Risks for death and program failure were estimated using Cox proportional hazard models. All regimens were compared with ZDV + 3TC + NVP. Between July 2007 and November 2010, 18,866 treatment-naive adults initiated ART: 18.2% on ZDV + 3TC + NVP, 1.8% on ZDV + 3TC + EFV, 36.2% on TDF + XTC + NVP, and 43.8% on TDF + XTC + EFV. When exposure was categorized by initial prescription, patients on TDF + XTC + NVP [adjusted hazard ratio (AHR): 1.45; 95% confidence interval (CI): 1.03 to 2.06] had a higher post-90-day mortality. TDF + XTC + NVP was also associated with an elevated risk for mortality when exposure was categorized as time-varying (AHR: 1.51; 95% CI: 1.18 to 1.95) or by predominant exposure over the first 90 days (AHR: 1.91, 95% CI: 1.09 to 3.34). However, these findings were not consistently observed across sensitivity analyses or when program failure was used as a secondary outcome. TDF + XTC + NVP was associated with higher mortality when compared with ZDV + 3TC + NVP but not consistently across sensitivity analyses. These findings may be explained in part by inherent limitations to our retrospective approach, including residual confounding. Further research is urgently needed to compare the effectiveness of ART regimens in use in resource-constrained settings.JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2011; 58(5):475-81. · 4.43 Impact Factor -
Article: Optimal time on HAART for prevention of mother-to-child transmission of HIV.
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ABSTRACT: To determine the impact of time between initiating highly active antiretroviral therapy (HAART) and delivery-duration of antenatal HAART-on perinatal HIV infection. We conducted a retrospective cohort analysis of pregnant HIV-infected women in Lusaka, Zambia. Women in our cohort were receiving HAART and had an infant HIV polymerase chain reaction test between 3 and 12 weeks of life. We examined factors associated with infant HIV infection and performed a locally weighted regression analysis to examine the effect of duration of antenatal HAART on perinatal HIV infection. : From January 2007 to March 2010, 1813 HIV-infected pregnant women met inclusion criteria. Mean gestational age at first antenatal visit was 21 weeks (SD ± 6), median CD4+ cell count was 231 cells per microliter (interquartile range: 164-329), and median duration of antenatal HAART was 13 weeks (interquartile range 8-19). Fifty-nine (3.3%) infants were HIV infected. Duration of antenatal HAART was the most important predictor of perinatal HIV transmission. Compared with women initiating HAART at least 13 weeks before delivery, women on HAART for ≤4 weeks had a 5.5-fold increased odds of HIV transmission (95% confidence interval: 2.6 to 11.7). Locally weighted regression analysis suggested limited additional prophylactic benefit beyond 13 weeks on antenatal HAART. Low rates of mother-to-child HIV transmission can be achieved within programmatic settings in Africa. Maximal effectiveness of prevention of mother-to-child transmission programs is achieved by initiating HAART at least 13 weeks before delivery.JAIDS Journal of Acquired Immune Deficiency Syndromes 06/2011; 58(2):224-8. · 4.43 Impact Factor -
Article: Determinants of stillbirth in Zambia.
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ABSTRACT: The objective of this study was to estimate the rates and determinants of stillbirth in an urban African obstetric population. In this retrospective cohort study, we reviewed vital outcomes of newborns whose mothers received antenatal care, delivery care, or both antenatal and delivery care in the Lusaka, Zambia, public sector between February 2006 and March 2009. We excluded newborns weighing less than 1,000 g, those whose mothers died before delivery, and those born outside Lusaka. There were 100,454 deliveries that met criteria for inclusion. The median maternal age at the initial visit was 24 years (interquartile range 21-29) and the median gestational age was 22 weeks (interquartile range 19-26). The median gestational age at birth was 38 weeks (interquartile range 36-40), and the median neonatal birth weight was 3,000 g (interquartile range 2,750-3,300). A total of 2,109 fetuses were stillborn (crude rate, 21 per 1,000 live births, 95% confidence interval 20.1 per 1,000 to 21.9 per 1,000). This included 1,049 (49.7%) stillbirths classified as "recent" (presumed to have occurred within 12 hours of delivery) and 1,060 (50.3%) classified as "macerated" (presumed to have occurred more than 12 hours before delivery). In adjusted analysis, increasing maternal age, baseline body mass index greater than 26, history of stillbirth, placental abruption, maternal untreated syphilis, cesarean delivery, operative vaginal delivery, assisted breech delivery, and extremes of neonatal birth weight were all significantly associated with stillbirth. Stillbirth is a major contributor to poor perinatal outcomes in Lusaka. Many deaths appear avoidable through investment in antenatal screening and better labor monitoring. Stillbirth should be adopted as a routine health indicator by the World Health Organization.Obstetrics and Gynecology 05/2011; 117(5):1151-9. · 4.73 Impact Factor -
Article: Predictors of CD4 eligibility for antiretroviral therapy initiation among HIV-infected pregnant women in Lusaka, Zambia.
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ABSTRACT: In resource-limited settings, CD4 testing is a barrier to antiretroviral therapy initiation in pregnancy. We used logistic regression to identify predictors of CD4 cell count ≤ 350 cells/uL in 20,233 pregnant women. The best-performing model included any 3 of: age ≥ 28 years old, hemoglobin ≤ 9.8 g/dL, gestational age ≤ 30 weeks, weight ≤ 64 kg, history of tuberculosis or previous death of an infant prior to one year old. Sensitivity was 45.7% (95% CI: 44.5-47.0), specificity 70.7% (95% CI: 69.6-71.8), and misclassification rate 41.4% (95% CI: 40.5-42.2). CD4 triage remains a critical element of maternal HIV care and PMTCT.JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2011; 57(5):e101-5. · 4.43 Impact Factor -
Article: Causes of stillbirth, neonatal death and early childhood death in rural Zambia by verbal autopsy assessments
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ABSTRACT: Objectives To describe specific causes of the high rates of stillbirth, neonatal death and early child childhood death in Zambia.Methods We conducted a household-based survey in rural Zambia. Socio-demographic and delivery characteristics were recorded, alongside a maternal HIV test. Verbal autopsy questionnaires were administered to elicit mortality-related information and independently reviewed by three experienced paediatricians who assigned a cause and contributing factor to death. For this secondary analysis, deaths were categorized into: stillbirths (foetal death ≥28 weeks of gestation), neonatal deaths (≤28 days) and early childhood deaths (>28 days to <2 years).Results Among 1679 households, information was collected on 148 deaths: 34% stillbirths, 26% neonatal and 40% early childhood deaths. Leading identifiable causes of stillbirth were intrauterine infection (26%) and birth asphyxia (18%). Of 32 neonatal deaths, 38 (84%) occurred within the first week of life, primarily because of infections (37%) and prematurity (34%). The majority of early childhood deaths were caused by suspected bacterial infections (82%). HIV prevalence was significantly higher in mothers who reported an early childhood death (44%) than mothers who did not (17%; P < 0.01). Factors significantly associated with mortality were lower socio-economic status (P < 0.01), inadequate water or sanitation facilities (P < 0.01), home delivery (P = 0.04) and absence of a trained delivery attendant (P < 0.01).Conclusion We provide community-level data about the causes of death among children under 2 years of age. Infectious etiologies for mortality ranked highest. At a public health level, such information may have an important role in guiding prevention and treatment strategies to address perinatal and early childhood mortality.Objectifs: Décrire les causes spécifiques des taux élevés de mortinatalité, de mortalité néonatale et de mortalité infantile chez les enfants en Zambie.Méthodes: Nous avons mené une enquête auprès des ménages en milieu rural en Zambie. Les caractéristiques sociodémographiques et celles des accouchements ont été enregistrées ainsi que le test VIH de la mère. Des questionnaires d’autopsie verbale ont été administrés afin d’obtenir des informations liées à la mortalité, indépendamment analysées par trois pédiatres expérimentés qui ont attribué une cause au décès et un facteur contribuant. Pour cette analyse secondaire, les décès ont été classés en: mortinatalité (mort fœtale ≥28 semaines de gestation), mortalité néonatale (≤28 jours) et mortalité infantile (≥28 jours et ≤2 ans).Résultats: Parmi les 1679 ménages étudiés, des informations ont été collectées pour 148 décès: mort-nés (34%), décès néonataux (26%) et décès de la petite enfance (40%). Les principales causes identifiables de mortinatalitéétaient l’infection intra-utérine (26%) et l’asphyxie à la naissance (18%). 32 des 38 (84%) décès néonataux sont survenus au cours de la première semaine de vie, principalement dus à des infections (37%) et à la prématurité (34%). La majorité des décès infantiles étaient dus à des d’infections bactériennes suspectés (82%). la prévalence du VIH était significativement plus élevée chez les mères qui ont déclaré un décès infantile (44%) que chez les autres (17%, p < 0,01). Les facteurs significativement associés à la mortalitéétaient le faible statut socioéconomique (p < 0,01), le manque d’eau ou d’assainissement des installations (p < 0,01), l’accouchement à domicile (p = 0,04) et l’absence d’un aide forméà l’accouchement (p < 0,01).Conclusion: Nous fournissons ici des données au niveau communautaire sur les causes de décès chez les enfants de moins de 2 ans. L’étiologie infectieuse pour la mortalité a été classée comme la plus forte. Au niveau de la santé publique, cette information peut avoir un rôle important dans l’orientation des stratégies de prévention et de traitement pour lutter contre la mortalité périnatale et celle de la petite enfance.Objetivos: Describir las causas específicas de las altas tasas de mortinato, muerte neonatal y muerte infantil temprana en Zambia.Métodos: Hemos realizado un estudio en hogares rurales de Zambia. Se recogieron datos socio-demográficos y características del parto, junto con los resultados de la prueba materna para VIH. Se administraron cuestionarios de autopsia verbal para obtener información relacionada con la mortalidad y estos fueron revisados de forma independiente por tres pediatras expertos que asignaron las causas de muerte y los factores que contribuyeron a la misma. Para este análisis secundario las muertes se catalogaron como mortinatos (muerte fetal ≥28 semanas de gestación), muertes neonatales (≤28 días), y muerte infantil temprana (>28 días a <2 años).Resultados: Entre 1679 hogares se recogió información sobre 148 muertes: 34% mortinatos; 26% neonatos; y 40% de muertes infantiles tempranas. Las principales causas identificables de mortinato eran la infección intrauterina (26%) y la asfixia durante el parto (18%). 32 de 38 (84%) muertes neonatales ocurrieron dentro de la primera semana de vida, principalmente debido a infecciones (37%) y prematuridad (34%). La mayoría de las muertes infantiles tempranas eran debidas a infecciones bacterianas (82%). La prevalencia de VIH era significativamente mayor entre madres que habían reportado una muerte infantil temprana (44%) que las madres que no lo habían hecho (17%; p < 0.01). Los factores significativamente asociados con la mortalidad eran un estatus socio-económico bajo (p < 0.01), unas instalaciones de agua o sanitarias inadecuadas (p < 0.01), tener el parto en casa (p = 0.04), y la ausencia de una partera entrenada durante el parto (p < 0.01).Conclusión: Hemos presentado datos a nivel comunitario sobre las causas de muerte entre niños menores de 2 años. La etiología infecciosa era la causa más común de mortalidad. A nivel de salud pública esta información puede tener un papel importante a la hora de establecer estrategias de prevención y tratamiento para tratar la mortalidad infantil y perinatal.Tropical Medicine & International Health 04/2011; 16(7):894 - 901. · 2.80 Impact Factor -
Article: Causes of stillbirth, neonatal death and early childhood death in rural Zambia by verbal autopsy assessments.
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ABSTRACT: To describe specific causes of the high rates of stillbirth, neonatal death and early child childhood death in Zambia. We conducted a household-based survey in rural Zambia. Socio-demographic and delivery characteristics were recorded, alongside a maternal HIV test. Verbal autopsy questionnaires were administered to elicit mortality-related information and independently reviewed by three experienced paediatricians who assigned a cause and contributing factor to death. For this secondary analysis, deaths were categorized into: stillbirths (foetal death ≥28 weeks of gestation), neonatal deaths (≤28 days) and early childhood deaths (>28 days to <2 years). Among 1679 households, information was collected on 148 deaths: 34% stillbirths, 26% neonatal and 40% early childhood deaths. Leading identifiable causes of stillbirth were intrauterine infection (26%) and birth asphyxia (18%). Of 32 neonatal deaths, 38 (84%) occurred within the first week of life, primarily because of infections (37%) and prematurity (34%). The majority of early childhood deaths were caused by suspected bacterial infections (82%). HIV prevalence was significantly higher in mothers who reported an early childhood death (44%) than mothers who did not (17%; P < 0.01). Factors significantly associated with mortality were lower socio-economic status (P < 0.01), inadequate water or sanitation facilities (P < 0.01), home delivery (P = 0.04) and absence of a trained delivery attendant (P < 0.01). We provide community-level data about the causes of death among children under 2 years of age. Infectious etiologies for mortality ranked highest. At a public health level, such information may have an important role in guiding prevention and treatment strategies to address perinatal and early childhood mortality.Tropical Medicine & International Health 04/2011; 16(7):894-901. · 2.80 Impact Factor -
Article: Implementation of the Zambia electronic perinatal record system for comprehensive prenatal and delivery care.
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ABSTRACT: To characterize prenatal and delivery care in an urban African setting. The Zambia Electronic Perinatal Record System (ZEPRS) was implemented to record demographic characteristics, past medical and obstetric history, prenatal care, and delivery and newborn care for pregnant women across 25 facilities in the Lusaka public health sector. From June 1, 2007, to January 31, 2010, 115552 pregnant women had prenatal and delivery information recorded in ZEPRS. Median gestation age at first prenatal visit was 23weeks (interquartile range [IQR] 19-26). Syphilis screening was documented in 95663 (83%) pregnancies: 2449 (2.6%) women tested positive, of whom 1589 (64.9%) were treated appropriately. 111108 (96%) women agreed to HIV testing, of whom 22% were diagnosed with HIV. Overall, 112813 (98%) of recorded pregnancies resulted in a live birth, and 2739 (2%) in a stillbirth. The median gestational age was 38weeks (IQR 35-40) at delivery; the median birth weight of newborns was 3000g (IQR 2700-3300g). The results demonstrate the feasibility of using a comprehensive electronic medical record in an urban African setting, and highlight its important role in ongoing efforts to improve clinical care.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 02/2011; 113(2):131-6. · 1.41 Impact Factor -
Article: Early immunologic response and subsequent survival among malnourished adults receiving antiretroviral therapy in Urban Zambia.
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ABSTRACT: To evaluate the relationship between early CD4(+) lymphocyte recovery on antiretroviral therapy (ART) and subsequent survival among low body mass index (BMI) HIV-1-infected adults. Retrospective analysis of a large programmatic cohort in Lusaka, Zambia. We evaluated ART-treated adults enrolled in care for more than 6 months. We stratified this study population according to World Health Organization (WHO) malnutrition criteria: normal (BMI >or=18.5 kg/m(2)), mild (17.00-18.49), moderate (16.00-16.99), and severe (<16.0). We used Cox proportional hazards regression to estimate the subsequent risk of death associated with absolute CD4(+) cell count change over the first 6 months on ART. To account for effect modification associated with baseline CD4(+) cell count, a weighted summary measure was calculated. From May 2004 to February 2009, 56,612 patients initiated ART at Lusaka district clinics; of these, 33 097 (58%) were included in this analysis. The median change in 0-6 month CD4(+) cell count in each baseline BMI strata varied from 127 to 131 cells/microl. There was a statistically significant, inverse association between baseline BMI and the post 6-month hazard for mortality only among those patients with less than 100 cells/microl increase in the first 6 months of ART. A CD4(+) cell count increase of at least 100 cells/microl over the first 6 months of ART was not associated with a higher hazard for mortality, regardless of baseline BMI. Low baseline BMI and attenuated CD4(+) cell count response at 6 months had a compounding, negative impact on post 6-month survival. Specific guidelines for monitoring ART response using immunologic criteria may be warranted for low BMI patients.AIDS (London, England) 08/2010; 24(13):2117-21. · 4.91 Impact Factor -
Article: Coverage of nevirapine-based services to prevent mother-to-child HIV transmission in 4 African countries.
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ABSTRACT: Few studies have objectively evaluated the coverage of services to prevent transmission of human immunodeficiency virus (HIV) from mother to child. To measure the coverage of services to prevent mother-to-child HIV transmission in 4 African countries. Cross-sectional surveillance study of mother-infant pairs using umbilical cord blood samples collected between June 10, 2007, and October 30, 2008, from 43 randomly selected facilities (grouped as 25 service clusters) providing delivery services in Cameroon, Côte d'Ivoire, South Africa, and Zambia. All sites used at least single-dose nevirapine to prevent mother-to-child HIV transmission and some sites used additional prophylaxis drugs. Population nevirapine coverage, defined as the proportion of HIV-exposed infants in the sample with both maternal nevirapine ingestion (confirmed by cord blood chromatography) and infant nevirapine ingestion (confirmed by direct observation). A total of 27,893 cord blood specimens were tested, of which 3324 were HIV seropositive (12%). Complete data for cord blood nevirapine results were available on 3196 HIV-seropositive mother-infant pairs. Nevirapine coverage varied significantly by site (range: 0%-82%). Adjusted for country, the overall coverage estimate was 51% (95% confidence interval [CI], 49%-53%). In multivariable analysis, failed coverage of nevirapine-based services was significantly associated with maternal age younger than 20 years (adjusted odds ratio [AOR], 1.44; 95% CI, 1.18-1.76) and maternal age between 20 and 25 years (AOR, 1.28; 95% CI, 1.07-1.54) vs maternal age of older than 30 years; 1 or fewer antenatal care visits (AOR, 2.91; 95% CI, 2.40-3.54), 2 or 3 antenatal care visits (AOR, 1.93; 95% CI, 1.60-2.33), and 4 or 5 antenatal care visits (AOR, 1.56; 95% CI, 1.34-1.80) vs 6 or more antenatal care visits; vaginal delivery (AOR, 1.22; 95% CI, 1.03-1.44) vs cesarean delivery; and infant birth weight of less than 2500 g (AOR, 1.34; 95% CI, 1.11-1.62) vs birth weight of 3500 g or greater. In this random sampling of sites with services to prevent mother-to-child HIV transmission, only 51% of HIV-exposed infants received the minimal regimen of single-dose nevirapine.JAMA The Journal of the American Medical Association 07/2010; 304(3):293-302. · 30.03 Impact Factor -
Article: Peripartum nevirapine exposure and subsequent clinical outcomes among HIV-infected women receiving antiretroviral therapy for at least 12 months.
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ABSTRACT: Prior exposure to intrapartum/neonatal nevirapine (NVP) is associated with compromised virologic treatment outcomes once non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) is initiated. We examined the longer-term clinical outcomes in a programmatic setting. We compared post-12 month mortality and clinical treatment failure (defined by WHO clinical and immunologic criteria) among women with and without prior NVP exposure in Lusaka, Zambia. Between April 2004 and July 2006, 6740 women initiated an NNRTI-containing regimen. At 12 months, 5172 (78%) remained active and were included in this analysis. Of these, 596 (12%) reported prior NVP exposure, whose time from exposure to ART initiation was: <6 months for 11%, 6-12 months for 13%, >12 months for 37%, unknown for 39%. Overall, women with prior NVP exposure trended towards increased survival (adjusted hazard ratio [AHR]: 0.53; 95% confidence interval [CI]: 0.27-1.06, P = 0.07) and towards increased hazard of clinical treatment failure (AHR: 1.18; 95% CI: 0.95-1.47, P = 0.14), particularly those with exposure for <6 months (AHR: 1.52; 95% CI: 0.94-2.45, P = 0.09). Prior NVP exposure appeared to increase risk for clinical treatment failure after 12 months of follow-up, but this finding did not reach statistical significance. With growing evidence linking recent NVP exposure to virologic failure, optimized monitoring algorithms should be considered for women with starting NNRTI-based ART. The association between prior NVP exposure and improved survival has not been previously shown and may be a result of residual confounding around health-seeking behaviours.Tropical Medicine & International Health 07/2010; 15(7):842-7. · 2.80 Impact Factor -
Article: Methods and baseline results of a repeated cross-sectional survey to assess the public health impact of antiretroviral therapy in Lusaka, Zambia.
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ABSTRACT: Although the individual-level impact of antiretroviral therapy (ART) is well documented, there are few available data describing the public health impact of services for persons infected with human immunodeficiency virus in resource-constrained settings. We describe the methods and baseline results of a household survey that assessed the population-level impact of the national program for HIV care in Zambia and treatment in the city of Lusaka. The survey was timed with the staggered expansion of services and repeated cross-sectional surveys planned for pre-implementation and post-implementation comparisons made by community. In the initial survey round, which was performed during the early phases of the program (November-December 2004), 18,110 persons were enumerated from 3,600 households surveyed. Respondents were asked questions designed to evaluate community-level mortality and respondent knowledge and attitudes towards HIV. These findings will serve as a reliable reference in the future analysis of the population-level impact of this HIV treatment and care program in Zambia.The American journal of tropical medicine and hygiene 05/2010; 82(5):971-7. · 2.59 Impact Factor
Top co-authors
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Institutions
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2012
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University of North Carolina at Chapel Hill
Chapel Hill, NC, USA
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2011–2012
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Centre for Infectious Disease Research in Zambia
Birmingham, AL, USA -
University of Alabama at Birmingham
Birmingham, AL, USA
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