Browsing by Author "Giganti MJ"

Now showing 1 - 17 of 17

Association between weight gain and clinical outcomes among malnourished adults initiating antiretroviral therapy in Lusaka, Zambia.
(2010-Apr-01) Koethe JR; Lukusa A; Giganti MJ; Chi BH; Nyirenda CK; Limbada MI; Banda Y; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. john.r.koethe@vanderbilt.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To describe the association between 6-month weight gain on antiretroviral therapy (ART) and subsequent clinical outcomes. DESIGN: A retrospective analysis of a large programmatic cohort in Lusaka, Zambia. METHODS: Using Kaplan-Meier analysis and Cox proportional hazards models, we examined the association between 6-month weight gain and the risk of subsequent death and clinical treatment failure. Because it is a known effect modifier, we stratified our analysis according to body mass index (BMI). RESULTS: Twenty-seven thousand nine hundred fifteen adults initiating ART were included in the analysis. Patients in the lower BMI categories demonstrated greater weight gain. In the post 6-month analysis, absolute weight loss was strongly associated with mortality across all BMI strata, with the highest risk observed among those with BMI <16 kg/m (adjusted hazard ratio 9.7; 95% CI: 4.7 to 20.0). There seemed to be an inverse relationship between weight gain and mortality among patients with BMI <16 kg/m. Similar trends were observed with clinical treatment failure. CONCLUSIONS: Weight gain after ART initiation is associated with improved survival and decreased risk for clinical failure, especially in the lower BMI strata. Prospective trials to promote weight gain after ART initiation among malnourished patients in resource-constrained settings are warranted.
Causes of stillbirth, neonatal death and early childhood death in rural Zambia by verbal autopsy assessments.
(2011-Jul) Turnbull E; Lembalemba MK; Guffey MB; Bolton-Moore C; Mubiana-Mbewe M; Chintu N; Giganti MJ; Nalubamba-Phiri M; Stringer EM; Stringer JS; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Comparative outcomes of tenofovir-based and zidovudine-based antiretroviral therapy regimens in Lusaka, Zambia.
(2011-Dec-15) Chi BH; Mwango A; Giganti MJ; Sikazwe I; Moyo C; Schuttner L; Mulenga LB; Bolton-Moore C; Chintu NT; Sheneberger R; Stringer EM; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Although tenofovir (TDF) is a common component of antiretroviral therapy (ART), recent evidence suggests inferior outcomes when it is combined with nevirapine (NVP). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Coverage of nevirapine-based services to prevent mother-to-child HIV transmission in 4 African countries.
(2010-Jul-21) Stringer EM; Ekouevi DK; Coetzee D; Tih PM; Creek TL; Stinson K; Giganti MJ; Welty TK; Chintu N; Chi BH; Wilfert CM; Shaffer N; Dabis F; Stringer JS; Centre for Infectious Disease Research in Zambia, Plot 1275 Lubutu Rd, PO Box 34681, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
CONTEXT: Few studies have objectively evaluated the coverage of services to prevent transmission of human immunodeficiency virus (HIV) from mother to child. OBJECTIVE: To measure the coverage of services to prevent mother-to-child HIV transmission in 4 African countries. DESIGN, SETTING, AND PATIENTS: 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. MAIN OUTCOME MEASURE: 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). RESULTS: 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. CONCLUSION: 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.
Determinants of stillbirth in Zambia.
(2011-May) Stringer EM; Vwalika B; Killam WP; Giganti MJ; Mbewe R; Chi BH; Chintu N; Rouse D; Goldenberg RL; Stringer JSA; From the University of Alabama at Birmingham School of Medicine, Birmingham, Alabama; the Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; the University Teaching Hospital, Ministry of Health Zambia, Lusaka, Zambia; the Ministry of Health Zambia, Ndeke House, Lusaka, Zambia; Brown University, Providence, Rhode Island; and Drexel University, Philadelphia, Pennsylvania.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: The objective of this study was to estimate the rates and determinants of stillbirth in an urban African obstetric population. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Early immunologic response and subsequent survival among malnourished adults receiving antiretroviral therapy in Urban Zambia.
(2010-Aug-24) Koethe JR; Limbada MI; Giganti MJ; Nyirenda CK; Mulenga L; Wester CW; Chi BH; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. john.r.koethe@vanderbilt.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: 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. DESIGN: Retrospective analysis of a large programmatic cohort in Lusaka, Zambia. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Effectiveness of generic and proprietary first-line anti-retroviral regimens in a primary health care setting in Lusaka, Zambia: a cohort study.
(2012-Apr) Stringer JS; Mwango AJ; Giganti MJ; Mulenga L; Levy JW; Stringer EM; Mulenga P; Saag MS; Musonda P; Williams FB; Reid SE; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. stringer@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Estimating the cost-effectiveness of nutrition supplementation for malnourished, HIV-infected adults starting antiretroviral therapy in a resource-constrained setting.
(2014) Koethe JR; Marseille E; Giganti MJ; Chi BH; Heimburger D; Stringer JS; Centre for Infectious Diseases Research in Zambia, Plot 5032 Great North Road, Lusaka, Zambia ; Division of Infectious Diseases, Vanderbilt University School of Medicine, 215 Light Hall, Nashville, TN 37232, USA.; Centre for Infectious Diseases Research in Zambia, Plot 5032 Great North Road, Lusaka, Zambia ; Vanderbilt Institute for Global Health, 2525 West End Ave., Nashville, TN 37203, USA.; Centre for Infectious Diseases Research in Zambia, Plot 5032 Great North Road, Lusaka, Zambia ; Department of Obstetrics and Gynecology, UNC Global Women's Health, University of North Carolina at Chapel Hill School of Medicine, 3009 Old Clinic Building CB #7570, Chapel Hill, NC 27599-7570, USA.; Health Strategies International, 555 59th Street, Oakland, CA 94609, USA.; Centre for Infectious Diseases Research in Zambia, Plot 5032 Great North Road, Lusaka, Zambia ; Department of Biostatistics, Vanderbilt University School of Medicine, 215 Light Hall, Nashville, TN 37232, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Low body mass index (BMI) individuals starting antiretroviral therapy (ART) for HIV infection in sub-Saharan Africa have high rates of death and loss to follow-up in the first 6 months of treatment. Nutritional supplementation may improve health outcomes in this population, but the anticipated benefit of any intervention should be commensurate with the cost given resource limitations and the need to expand access to ART in the region. METHODS: We used Markov models incorporating historical data and program-wide estimates of treatment costs and health benefits from the Zambian national ART program to estimate the improvements in 6-month survival and program retention among malnourished adults necessary for a combined nutrition support and ART treatment program to maintain cost-effectiveness parity with ART treatment alone. Patients were stratified according to World Health Organization criteria for severe (BMI <16.0 kg/m(2)), moderate (16.00-16.99 kg/m(2)), and mild (17.00-18.49 kg/m(2)) malnutrition categories. RESULTS: 19,247 patients contributed data between May 2004 and October 2010. Quarterly survival and retention were lowest in the BMI <16.0 kg/m(2) category compared to higher BMI levels, and there was less variation in both measures across BMI strata after 180 days. ART treatment was estimated to cost $556 per year and averted 7.3 disability-adjusted life years. To maintain cost-effectiveness parity with ART alone, a supplement needed to cost $10.99 per quarter and confer a 20% reduction in both 6-month mortality and loss to follow-up among BMI <16.0 kg/m(2) patients. Among BMI 17.00-18.49 kg/m(2) patients, supplement costs accompanying a 20% reduction in mortality and loss to follow-up could not exceed $5.18 per quarter. In sensitivity analyses, the maximum permitted supplement cost increased if the ART program cost rose, and fell if patients classified as lost to follow-up at 6 months subsequently returned to care. CONCLUSIONS: Low BMI adults starting ART in sub-Saharan Africa are at high risk of early mortality and loss to follow-up. The expense of providing nutrition supplementation would require only modest improvements in survival and program retention to be cost-effective for the most severely malnourished individuals starting ART, but interventions are unlikely to be cost-effective among those in higher BMI strata.
Evaluation of a Task-Shifting Strategy Involving Peer Educators in HIV Care and Treatment Clinics in Lusaka, Zambia.
(2012-Mar-07) Born LJ; Wamulume C; Neroda KA; Quiterio N; Giganti MJ; Morris M; Bolton-Moore C; Baird S; Sinkamba M; Topp SM; Reid SE; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; University of Alabama at Birmingham, Alabama, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, USA.; Centre for Infectious Disease Research in Zambia , Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; University of Washington, Seattle, Washington, USA.; Harvard Medical School , Boston, Massachusetts, USA.; Lusaka District Health Management Team , Lusaka, Zambia.; Emory University School of Medicine , Atlanta, Georgia, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Rapid expansion of antiretroviral therapy (ART) and a shortage of health care workers (HCWs) required the implementation of a peer educator (PE) model as part of a task-shifting strategy in Lusaka District clinics. The purpose of this study was to evaluate patient and staff perceptions regarding whether the PE program: a) relieved the workload on professional HCWs; and b) delivered services of acceptable quality. Qualitative and quantitative data were gathered from five primary care clinics delivering ART in Lusaka, Zambia. Closed surveys were conducted with 148 patients receiving ART, 29 PEs, and 53 HCWs. Data was imported into Microsoft Excel to calculate descriptive statistics. Six focus group discussions and eight key informant (KI) interviews were conducted, recorded, transcribed, and coded to extract relevant data. Survey results demonstrated that 50 of 53 (96.1%) HCWs agreed PEs reduced the amount of counseling duties required of HCWs. HCWs felt that PEs performed as well as HCWs in counseling patients (48 of 53; 90.6%) and that having PEs conduct counseling enabled clinical staff to see more patients (44 of 53; 83%). A majority of patients (141 of 148; 95.2%) agreed or strongly agreed that PEs were knowledgeable about ART, and 89 of 144 (61.8%) expressed a high level of confidence with PEs performing counseling and related tasks. Focus group and KI interviews supported these findings. PEs helped ease the work burden of HCWs and provided effective counseling, education talks, and adherence support to patients in HIV care. Consideration should be given to formalizing their role in the public health sector.
Implementation of the Zambia electronic perinatal record system for comprehensive prenatal and delivery care.
(2011-May) Chi BH; Vwalika B; Killam WP; Wamalume C; Giganti MJ; Mbewe R; Stringer EM; Chintu NT; Putta NB; Liu KC; Chibwesha CJ; Rouse DJ; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To characterize prenatal and delivery care in an urban African setting. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
Measuring coverage in MNCH: population HIV-free survival among children under two years of age in four African countries.
(2013) Stringer JS; Stinson K; Tih PM; Giganti MJ; Ekouevi DK; Creek TL; Welty TK; Chi BH; Wilfert CM; Shaffer N; Stringer EM; Dabis F; Coetzee D; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. jeff_stringer@unc.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.
Methods and baseline results of a repeated cross-sectional survey to assess the public health impact of antiretroviral therapy in Lusaka, Zambia.
(2010-May) Giganti MJ; Levy JW; Banda Y; Kusanthan T; Sinkala M; Stringer JS; Chi BH; Centre for Infectious Disease Research in Zambia, Box 34681, Plot 1275, Lubuto Road, Lusaka, Zambia. mark.giganti@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Nonvirologic algorithms for predicting HIV infection among HIV-exposed infants younger than 12 weeks of age.
(2013-Feb) Chi BH; Limbada MI; Giganti MJ; Li MS; Bweupe M; Musonda P; Bubala P; Mubiana-Mbewe M; Chintu NT; Bolton-Moore C; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Early initiation of antiretroviral therapy 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 younger than 12 weeks of age. We evaluated algorithm performance for all possible combinations of selected characteristics 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 had HIV diagnosed. We evaluated 382,155,260 different characteristic combinations for predicting infant HIV infection. The algorithm with the highest combined sensitivity and specificity required 5 of the following 7 characteristic thresholds: infant CD8 percentage >22; infant CD4 percentage ≤44; infant weight-for-age Z score ≤0; infant CD4 ≤1600 cells/µL; infant CD8 >2200 cells/µL; maternal CD4 ≤600 cells/µL; and mother not currently using antiretroviral therapy for HIV treatment. This combination had a sensitivity of 90.3%, specificity of 78.4%, positive predictive value of 22.4%, negative predictive value of 99.2% and area under the curve of 0.844. CONCLUSION: Predicting HIV infection in HIV-exposed infants in this age group is difficult using clinical and immunologic characteristics. Expansion of polymerase chain reaction capacity in resource-limited settings remains urgently needed.
Optimal time on HAART for prevention of mother-to-child transmission of HIV.
(2011-Oct-01) Chibwesha CJ; Giganti MJ; Putta N; Chintu N; Mulindwa J; Dorton BJ; Chi BH; Stringer JS; Stringer EM; University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA. Carla.Chibwesha@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVES: To determine the impact of time between initiating highly active antiretroviral therapy (HAART) and delivery-duration of antenatal HAART-on perinatal HIV infection. DESIGN: 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. METHODS: 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. RESULTS: : 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. CONCLUSIONS: 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.
Peripartum nevirapine exposure and subsequent clinical outcomes among HIV-infected women receiving antiretroviral therapy for at least 12 months.
(2010-Jul) Chintu N; Giganti MJ; Putta NB; Sinkala M; Sadoki E; Stringer EM; Stringer JS; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Predictors of CD4 eligibility for antiretroviral therapy initiation among HIV-infected pregnant women in Lusaka, Zambia.
(2011-Aug-15) Liu KC; Mulindwa J; Giganti MJ; Putta NB; Chintu N; Chi BH; Stringer JS; Stringer EM; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. cherry.liu@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: In resource-limited settings, CD4 testing is a barrier to antiretroviral therapy initiation in pregnancy. METHODS: We used logistic regression to identify predictors of CD4 cell count ≤ 350 cells/uL in 20,233 pregnant women. RESULTS: 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). CONCLUSION: CD4 triage remains a critical element of maternal HIV care and PMTCT.
Six-month hemoglobin concentration and its association with subsequent mortality among adults on antiretroviral therapy in Lusaka, Zambia.
(2012-Sep-01) Giganti MJ; Limbada M; Mwango A; Moyo C; Mulenga LB; Guffey MB; Mulenga PL; Bolton-Moore C; Stringer JS; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. giganticidrz@gmail.com; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.