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Welcome to the CIDRZ Published Research Collection. This collection serves as a central repository of peer-reviewed publications authored, co-authored, or supported by the Centre for Infectious Disease Research in Zambia (CIDRZ). It provides open access to scientific knowledge that contributes to public health, clinical research, and evidence-based policy in Zambia and beyond.

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Antiretroviral therapy in sub-Saharan Africa: adherence lessons from tuberculosis and leprosy.
(2004-Nov) Reid SE; Reid CA; Vermund SH; Centre for Infectious Disease Research in Zambia, PO Box 34681, Plot 5977 Benakale Road, Northmead, Lusaka, Zambia. stewart@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Declining drug costs and increases in international donor interest are leading to greater availability of antiretroviral treatment programmes for persons living with the human immunodeficiency virus in parts of sub-Saharan Africa. Ensuring adequate adherence to antiretroviral drug therapy is one of the principal challenges facing successful implementation in Africa, where 70% of the world's infected persons live. Tuberculosis and leprosy are two diseases of global importance whose control programmes can provide important lessons for developing antiretroviral drug adherence strategies. This paper examines various approaches used in tuberculosis and leprosy control which could help enhance adherence to antiretroviral therapy in resource-limited settings.
Perceptions toward HIV, HIV screening, and the use of antiretroviral medications: a survey of maternity-based health care providers in Zambia.
(2004-Oct) Chi BH; Chansa K; Gardner MO; Sangi-Haghpeykar H; Goldenberg RL; Sinkala M; Muchimba M; Stringer JS; Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, USA. Bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Mother-to-child transmission of HIV (MTCT) is a major contributor to Zambia's HIV burden. Based on our experience in Zambia, we felt that provider perceptions, knowledge base, and practice patterns toward HIV-positive mothers may pose as significant obstacles to preventing MTCT. Two hundred and twenty-five health care providers throughout Zambia were surveyed in 2002. Providers reported widespread stigma associated with HIV. Physicians (OR = 1.9), providers with research affiliations (OR = 2.3), and those located in Lusaka (OR = 9.0) were more likely to offer HIV testing. Only 30% routinely prescribed antiretroviral treatment (ART) to reduce MTCT. Practitioners from district facilities, those from Lusaka, and those employed at research facilities were more likely to prescribe ART routinely (OR = 2.8, 10.1 and 3.4 respectively). Among those never prescribing ART, most cited a lack of availability (83%). Our results highlight the need for further provider education, critical appraisal of the current system for HIV testing, and widespread distribution of ART.
Effectiveness of a city-wide program to prevent mother-to-child HIV transmission in Lusaka, Zambia.
(2005-Aug-12) Stringer JS; Sinkala M; Maclean CC; Levy J; Kankasa C; Degroot A; Stringer EM; Acosta EP; Goldenberg RL; Vermund SH; Schools of Medicine and Public Health, University of Alabama at Birmingham, USA. stringer@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To determine the population effectiveness of a city-wide perinatal HIV prevention program. DESIGN: An anonymous surveillance of newborn cord blood for HIV serology and nevirapine (NVP). METHODS: All 10 public-sector delivery centers in Lusaka, Zambia participated. All mother-infant pairs delivering during the 12-week surveillance period at the participating centers and who received antenatal care at a public-sector facility in Lusaka were included in the study. The main outcome measure was population NVP coverage, defined as the proportion of HIV-infected women and HIV-exposed infants in the population that ingested NVP. RESULTS: Of 8787 women in the surveillance population, 7204 (82%) had been offered antenatal HIV testing, of which 5149 (71%) had accepted, and of which 5129 (99%) had received a result. Overall, 2257 of 8787 (26%) were cord seropositive. Of the 1246 (55%) cord blood seropositive women who received an antenatal HIV test result, 1112 (89%) received a positive result; the other 134 comprise seroconverters and clerical errors. Only 751 of 1112 (68%) women who received a positive antenatal test result and a NVP tablet for ingestion at labor onset had NVP detected in the cord blood (i.e., maternal non-adherence rate was 32%). A total of 675 infants born to 751 adherent mothers (90%) received NVP before discharge. Thus, only 675 of 2257 (30%) seropositive mother-infant pairs in the surveillance population received both a maternal and infant dose of NVP. CONCLUSIONS: Successful perinatal HIV prevention requires each mother-infant pair to negotiate a cascade of events that begins with offering HIV testing and continues through adherence to the prescribed regimen. This novel surveillance demonstrates that failures occur at each step, resulting in reduced coverage and diminished program effectiveness.
Cost and enrollment implications of targeting different source population for an HIV treatment program.
(2005-Nov-01) Chi BH; Fusco H; Sinkala M; Goldenberg RL; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Rapid scale-up of antiretroviral therapy (ART) is a worldwide priority, and ambitious targets for numbers on ART have been set. Antenatal clinics (ANCs) and tuberculosis (TB) clinics have been targeted as entry points into HIV care. METHODS: We developed a conditional probability model to evaluate the effects of ANC and TB clinic populations on ART program enrollment. RESULTS: To start 1 individual on ART, 3 TB patients have to be screened at a crude program cost of 36 US dollars per patient initiated on therapy. By contrast, 48 ANC patients have to be screened at a cost of US 214 US dollars per patient on therapy. In an incremental analysis in which ANC HIV testing was borne by a program to prevent mother-to-child transmission, recruitment efficiency increased (8 screened per patient starting ART) and cost decreased (114 US dollars per patient on therapy). Absolute numbers starting ART, however, remained fixed. If all 60,000 ANC patients seen yearly in the Lusaka District were screened, 1247 would start ART. Approaching the district's 35,000 annual TB patients would generate 11,947 patients on ART. CONCLUSION: In areas with high HIV prevalence, targeting chronically ill populations for HIV treatment may have significant short-term benefits in cost savings and recruitment efficiency.
Timing of maternal and neonatal dosing of nevirapine and the risk of mother-to-child transmission of HIV-1: HIVNET 024.
(2005-Nov-04) Chi BH; Wang L; Read JS; Sheriff M; Fiscus S; Brown ER; Taha TE; Valentine M; Goldenberg R; University of Alabama at Birmingham, Department of Obstetrics & Gynecology, Birmingham, Alabama, USA. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: Despite a growing emphasis worldwide on complex and potent antiretroviral drug regimens for the prevention of mother-to-child transmission of HIV-1 (MTCT), two-dose nevirapine (NVP) prophylaxis remains an important choice in many settings. We analyzed data from a multicenter clinical trial to determine whether timing of maternal or infant NVP was associated with MTCT between delivery and 6 weeks of age (intrapartum/early postnatal transmission; I/EP). METHODS: HIVNET 024 was a placebo-controlled, double-blind trial of empiric antibiotics to reduce chorioamnionitis-associated MTCT. This secondary analysis used data collected in the original randomized trial. Enrolled women were instructed to self-administer NVP at labor onset; infants were to receive a dose within 72 h of birth. RESULTS: Data regarding 1491 mother-infant pairs were analyzed. The overall I/EP HIV-1 transmission rate was 8.1% at 6 weeks. Almost all women (93%) ingested NVP within 24 h of delivery; 90% of infants were given NVP within 48 h after delivery. Variations in mother or infant dose timing did not influence transmission rates, even when the combined pattern of both was taken into account through multivariate analysis. In the subset of women ingesting NVP or= 4 h). CONCLUSION: Variations in the timing of maternal and infant NVP doses (within reasonable proximity to delivery) do not appear to affect the risk of MTCT.
Field performance of a thin-layer chromatography assay for detection of nevirapine in umbilical cord blood.
(2006) Chi BH; Lee A; Acosta EP; Westerman LE; Sinkala M; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
PURPOSE: Although cord blood surveillance can measure the effectiveness of nevirapine (NVP)-based programs for the prevention of mother-to-child HIV transmission (PMTCT), it requires the ability to detect nevirapine in plasma. At present, the only validated method is high-performance liquid chromatography (HPLC), a technique poorly suited for most resource-constrained settings. METHOD: We evaluated the field performance for a simple and inexpensive thin-layer chromatography (TLC) assay for NVP detection. We developed a conditional probability model to compare 2 testing algorithms: HPLC alone, and TLC screening followed by HPLC confirmation of negative results. RESULTS: When compared to HPLC, sensitivity of TLC was 0.67 (95% confidence interval [CI] 0.49-0.84) and specificity was 0.84 (95% CI 0.69-0.95). In this sample - where overall NVP coverage was 49% - positive predictive value was 0.80 and negative predictive value was 0.72. At baseline with population NVP coverage of 33%, cost per specimen was lower in the TLC-HPLC testing algorithm (40 dollars vs. 50 dollars), and the proportion of false results was acceptable (11%). As population NVP coverage increased, cost-efficiency improved and error rate dropped substantially. CONCLUSION: TLC is reasonably sensitive and specific for NVP detection. A 2-step testing algorithm incorporating TLC and HPLC provides cost-efficiency at little expense to test performance.
HIVCorps: using volunteers to rapidly expand HIV health services across Zambia.
(2006-May) Chi BH; Fusco H; Goma FM; Zulu I; Simmers E; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
In 2004, we created HIVCorps, an international volunteer program to involve pre-medical, medical, and public health students in the scale-up of HIV care and prevention services in Zambia. In our first year, we used 27 American and Zambian volunteers to assist with the administrative and logistical aspects of program implementation. Ten volunteers were based in the capital Lusaka; the remaining 17 were stationed across five rural districts. Supervision was provided by local health care providers, district officials, and hospital administrators. In our setting, the use of volunteers has proven feasible and effective for program support. Depending on a program's immediate needs, use of many basic field personnel may be more beneficial than employment of one to two trained clinicians. Formal volunteer programs like HIVCorps should be developed alongside initiatives focused on deploying more specialized, experienced healthcare workers aboard.
Isolation and characterization of a new simian rotavirus, YK-1.
(2006-May-31) Westerman LE; Jiang B; McClure HM; Snipes-Magaldi LJ; Griffin DD; Shin G; Gentsch JR; Glass RI; Viral Gastroenteritis Team, Respiratory and Enteric Viruses Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. larry@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: To effectively analyze the requirements for protection to rotavirus infection, a reliable animal model that reasonably mimics infection and disease in humans is needed. A requirement for an effective animal model is the availability of appropriate rotavirus stocks for challenge. RESULTS: A new simian rotavirus, designated YK-1, was isolated from a 2-year-old immunodeficient pigtailed macaque with chronic diarrhea. YK-1 was distinguishable by electropherotype from the other simian rotavirus strains, SA11 and RRV. One variant of YK-1, clone 311, which was isolated after adaptation and plaque purification in cell cultures, displayed an unusual RNA electropherotype with an abnormally migrating gene 11 segment. Sequence analysis demonstrated a genetic rearrangement that involved a partial duplication of the gene 11 ORF encoding NSP5. YK-1 was identified as a Group A rotavirus belonging to subgroup 1. To further characterize the YK-1 strain, the genes encoding VP4, VP7, and NSP4 were sequenced. Analysis of VP4 and VP7 gene fragments suggests that this strain is a G3P3 rotavirus and is closely related to the simian rotavirus strain RRV. Serotype analysis also identified YK-1 as a G3 rotavirus. The NSP4 genotype of YK-1 is C, the same genotype as RRV. CONCLUSION: This newly isolated rotavirus, YK-1, is being used to establish a nonhuman primate model for studying the infectivity, immunity, and pathogenesis of rotavirus and for evaluating candidate rotavirus vaccines.
Use of traditional medicine among pregnant women in Lusaka, Zambia.
(2007) Banda Y; Chapman V; Goldenberg RL; Stringer JS; Culhane JF; Sinkala M; Vermund SH; Chi BH; University of Zambia School of Medicine, Lusaka, Zambia. yolan.banda@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: We studied the prevalence of and predictors for traditional medicine use among pregnant women seeking care in the Lusaka, Zambia public health system. SUBJECTS: We surveyed 1128 pregnant women enrolled in a clinical trial of perinatal human immunodeficiency virus (HIV) prevention strategies at two district delivery centers. OUTCOME MEASURES: Postpartum questionnaires were administered to determine demographic characteristics, behavioral characteristics, HIV knowledge, and prior use of traditional medicines. RESULTS: Of the 1128 women enrolled, 335 (30%) reported visiting a traditional healer in the past; 237 (21%) reported using a traditional healer during the current pregnancy. Overall, 54% believed that admitting to a visit to a traditional healer would result in worse medical care. When women who had used traditional medicines were compared to those who had not, no demographic differences were noted. However, women who reported use of traditional medicine were more likely to drink alcohol during pregnancy, have >or=2 sex partners, engage in "dry sex," initiate sex with their partner, report a previously treated sexually transmitted disease, and use contraception (all p < 0.01). HIV-infected women who reported using traditional healers were also less likely to adhere to a proven medical regimen to reduce HIV transmission to their infant (25% versus 50%, p = 0.048). CONCLUSIONS: Use of traditional medicine during pregnancy is common, stigmatized, and may be associated with nonadherence to antiretroviral regimens. Health care providers must open lines of communication with traditional healers and with pregnant women themselves to maximize program success.
A randomized trial of the intrauterine contraceptive device vs hormonal contraception in women who are infected with the human immunodeficiency virus.
(2007-Aug) Stringer EM; Kaseba C; Levy J; Sinkala M; Goldenberg RL; Chi BH; Matongo I; Vermund SH; Mwanahamuntu M; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. eli@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: The purpose of this study was to determine whether the intrauterine contraceptive device (IUD) is effective and safe among women who are infected with the human immunodeficiency virus (HIV). STUDY DESIGN: We randomly assigned 599 postpartum, HIV-infected women in Zambia to receive either a copper IUD or hormonal contraception and followed them for at least 2 years. RESULTS: Women who were assigned randomly to hormonal contraception were more likely to become pregnant than those who were assigned randomly to receive an IUD (rate, 4.6/100 vs 2.0/100 woman-years; hazards ratio, 2.4; 95% CI, 1.3-4.7). One woman who was assigned to the IUD experienced pelvic inflammatory disease (crude rate, 0.16/100 woman-years; 95% CI, 0.004-868); there was no pelvic inflammatory disease among those women who were assigned to hormonal contraception. Clinical disease progression (death or CD4+ lymphocyte count dropping below 200 cells/microL) was more common in women who were allocated to hormonal contraception (13.2/100 woman-years) than in women who were allocated to the IUD (8.6/100 woman-years; hazard ratio, 1.5; 95% CI, 1.04-2.1). CONCLUSION: The IUD is effective and safe in HIV-infected women. The unexpected observation that hormonal contraception was associated with more rapid HIV disease progression requires urgent further study.
Early clinical and immune response to NNRTI-based antiretroviral therapy among women with prior exposure to single-dose nevirapine.
(2007-May-11) Chi BH; Sinkala M; Stringer EM; Cantrell RA; Mtonga V; Bulterys M; Zulu I; Kankasa C; Wilfert C; Weidle PJ; Vermund SH; Stringer JS; Centre for Infectious Disease Research in Zambia, Zambia. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To determine whether prior exposure to single-dose nevirapine (NVP) for prevention of mother-to-child HIV transmission (PMTCT) is associated with attenuated CD4 cell response, death, or clinical treatment failure in women starting antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTI). METHODS: Open cohort evaluation of outcomes for women in program sites across Zambia. HIV treatment was provided according to Zambian/World Health Organization guidelines. RESULTS: Peripartum NVP exposure status was known for 6740 women initiating NNRTI-containing ART, of whom 751 (11%) reported prior use of NVP for PMTCT. There was no significant difference in mean CD4 cell change between those exposed or unexposed to NVP at 6 (+202 versus +182 cells/microl; P = 0.20) or 12 (+201 versus +211 cells/microl; P = 0.60) months. Multivariable analyses showed no significant differences in mortality [adjusted hazard ratio (HR), 1.2; 95% confidence interval (CI), 0.8-1.8] or clinical treatment failure (adjusted HR, 1.1; 95% CI, 0.8-1.5). Comparison of recent NVP exposure with remote exposure suggested a less favorable CD4 cell response at 6 (+150 versus +219 cells/microl; P = 0.06) and 12 (+149 versus +215 cells/microl; P = 0.39) months. Women with recent NVP exposure also had a trend towards elevated risk for clinical treatment failure (adjusted HR, 1.6; 95% CI, 0.9-2.7). CONCLUSION: Exposure to maternal single-dose NVP was not associated with substantially different short-term treatment outcomes. However, evidence was suggestive that exposure within 6 months of ART initiation may be a risk factor for poor treatment outcomes, highlighting the importance of ART screening and initiation early in pregnancy.
Predictors of stillbirth in sub-saharan Africa.
(2007-Nov) Chi BH; Wang L; Read JS; Taha TE; Sinkala M; Brown ER; Valentine M; Martinson F; Goldenberg RL; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To describe the incidence and predictors of stillbirth in a predominantly human immunodeficiency virus (HIV)-infected African cohort. METHODS: Human Immunodeficiency Virus (HIV) Prevention Trials Network (HPTN) 024 was a randomized controlled trial of empiric antibiotics to reduce chorioamnionitis-related perinatal HIV transmission. A proportion of HIV-uninfected individuals were enrolled to reduce community-based stigma surrounding the trial. For this analysis, only women who gave birth to singleton infants were included. RESULTS: Of 2,659 women enrolled, 2,434 (92%) mother- child pairs met inclusion criteria. Of these, 2,099 (86%) infants were born to HIV-infected women, and 335 (14%) were born to HIV-uninfected women. The overall stillbirth rate was 32.9 per 1,000 deliveries (95% confidence interval [CI] 26.1-40.7). In univariable analyses, predictors for stillbirth included previous stillbirth (odds ratio [OR] 2.3, 95% CI 1.2-4.3), antenatal hemorrhage (OR 14.4, 95% CI 4.3-47.9), clinical chorioamnionitis (OR 20.9, 95% CI 5.1-86.2), and marked polymorphonuclear infiltration on placental histology (OR 2.9, 95% CI 1.7-5.2). When compared with pregnancies longer than 37 weeks, those at 34-37 weeks (OR 1.7, 95% CI 0.8-3.4) and those at less than 34 weeks (OR 22.8, 95% CI 13.6-38.2) appeared more likely to result in stillborn delivery. Human immunodeficiency virus infection was not associated with a greater risk for stillbirth in either univariable (OR 1.5, 95% CI 0.7-3.0) or multivariable (adjusted OR 1.11, 95% CI 0.38-3.26) analysis. Among HIV-infected women, however, decreasing CD4 cell count was inversely related to stillbirth risk (P=.009). CONCLUSION: In this large cohort, HIV infection was not associated with increased stillbirth risk. Further work is needed to elucidate the relationship between chorioamnionitis and stillbirth in African populations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00021671 LEVEL OF EVIDENCE: II.
Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trial.
(2007-Nov-17) Chi BH; Sinkala M; Mbewe F; Cantrell RA; Kruse G; Chintu N; Aldrovandi GM; Stringer EM; Kankasa C; Safrit JT; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Intrapartum and neonatal single-dose nevirapine are essential components of perinatal HIV prevention in resource-constrained settings, but can induce resistance to other non-nucleoside reverse transcriptase inhibitor drugs. We aimed to investigate whether this complication would be reduced with a single peripartum intervention of tenofovir and emtricitabine. METHODS: We randomly assigned 400 HIV-infected pregnant women who sought care at two public-sector primary health facilities in Lusaka, Zambia. One was excluded, 200 were assigned to receive a single oral dose of 300 mg tenofovir disoproxil fumarate with 200 mg emtricitabine under direct observation, and 199 to receive no study drug. Short-course zidovudine and intrapartum nevirapine were offered to all HIV-infected women, according to the local standard of care. Women who met national criteria for antiretroviral therapy were referred for care and not enrolled. Our primary study outcome was resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery. We used standard population sequencing to determine HIV genotypes. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00204308. FINDINGS: Of the 200 women who were randomly assigned to the intervention, 14 were lost to follow-up or withdrew from the study, two did not take study drug according to protocol, and one specimen was lost; 23 of 199 controls were lost to follow-up or withdrew from the study, and three specimens were lost. Women given the intervention were 53% less likely than controls to have a mutation that conferred resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery (20/173 [12%] vs 41/166 [25%]; risk ratio [RR] 0.47, 95% CI 0.29-0.76). We noted postpartum anaemia, the most common serious adverse event in mothers, in four women in each group. 20 of 198 (10%) infants in the intervention group and 23 of 199 (12%) controls had a serious adverse event, mostly due to septicaemia (n=22) or pneumonia (n=8); these events did not differ between groups, and none were judged to be caused by the study intervention. INTERPRETATION: A single dose of tenofovir and emtricitabine at delivery reduced resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery by half; therefore this treatment should be considered as an adjuvant to intrapartum nevirapine.
Strategies for achieving healthy energy balance among African Americans in the Mississippi Delta.
(2007-Oct) Parham GP; Scarinci IC; Department of Medicine Room 126, Bevill Research Bldg, University of Alabama at Birmingham, Birmingham, AL 35294, USA. gparham@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: Low-income African Americans who live in rural areas of the Deep South are particularly vulnerable to diseases associated with unhealthy energy imbalance. The Centers for Disease Control and Prevention (CDC) has suggested various physical activity strategies to achieve healthy energy balance. Our objective was to conduct formal, open-ended discussions with low-income African Americans in the Mississippi Delta to determine 1) their dietary habits and physical activity levels, 2) their attitudes toward CDC's suggested physical activity strategies, and 3) their suggestions on how to achieve CDC's strategies within their own environment. METHODS: A qualitative method (focus groups) was used to conduct the study during 2005. Prestudy meetings were held with African American lay health workers to formulate a focus group topic guide, establish inclusion criteria for focus group participants, select meeting sites and times, and determine group segmentation guidelines. Focus groups were divided into two phases. RESULTS: All discussions and focus group meetings were held in community centers within African American neighborhoods in the Mississippi Delta and were led by trained African American moderators. Phase I focus groups identified the following themes: overeating, low self-esteem, low income, lack of physical exercise, unhealthy methods of food preparation, a poor working definition of healthy energy balance, and superficial knowledge of strategies for achieving healthy energy balance. Phase 2 focus groups identified a preference for social support-based strategies for increasing physical activity levels. CONCLUSION: Energy balance strategies targeting low-income, rural African Americans in the Deep South may be more effective if they emphasize social interaction at the community and family levels and incorporate the concept of community volunteerism.
Clinical outcomes and CD4 cell response in children receiving antiretroviral therapy at primary health care facilities in Zambia.
(2007-Oct-24) Bolton-Moore C; Mubiana-Mbewe M; Cantrell RA; Chintu N; Stringer EM; Chi BH; Sinkala M; Kankasa C; Wilson CM; Wilfert CM; Mwango A; Levy J; Abrams EJ; Bulterys M; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
CONTEXT: The Zambian Ministry of Health provides pediatric antiretroviral therapy (ART) at primary care clinics in Lusaka, where, despite scale-up of perinatal prevention efforts, many children are already infected with the human immunodeficiency virus (HIV). OBJECTIVE: To report early clinical and immunologic outcomes of children enrolled in the pediatric treatment program. DESIGN, SETTING, AND PATIENTS: Open cohort assessment using routinely collected clinical and outcome data from an electronic medical record system in use at 18 government primary health facilities in Lusaka, Zambia. Care was provided primarily by nurses and clinical officers ("physician extenders" akin to physician assistants in the United States). Patients were children (<16 years of age) presenting for HIV care between May 1, 2004, and June 29, 2007. INTERVENTION: Three-drug ART (zidovudine or stavudine plus lamivudine plus nevirapine or efavirenz) for children who met national treatment criteria. MAIN OUTCOME MEASURES: Survival, weight gain, CD4 cell count, and hemoglobin response. RESULTS: After enrollment of 4975 children into HIV care, 2938 (59.1%) started ART. Of those initiating ART, the median age was 81 months (interquartile range, 36-125), 1531 (52.1%) were female, and 2087 (72.4%) with World Health Organization stage information were in stage III or IV. At the time of analysis, 158 children (5.4%) had withdrawn from care and 382 (13.0%) were at least 30 days late for follow-up. Of the remaining 2398 children receiving ART, 198 (8.3%) died over 3018 child-years of follow-up (mortality rate, 6.6 deaths per 100 child-years; 95% confidence interval [CI], 5.7-7.5); of these deaths, 112 (56.6%) occurred within 90 days of therapy initiation (early mortality rate, 17.4/100 child-years; post-90-day mortality rate, 2.9/100 child-years). Mortality was associated with CD4 cell depletion, lower weight-for-age, younger age, and anemia in multivariate analysis. The mean CD4 cell percentage at ART initiation among the 1561 children who had at least 1 repeat measurement was 12.9% (95% CI, 12.5%-13.3%) and increased to 23.7% (95% CI, 23.1%-24.3%) at 6 months, 27.0% (95% CI, 26.3%-27.6%) at 12 months, 28.0% (95% CI, 27.2%-28.8%) at 18 months, and 28.4% (95% CI, 27.4%-29.4%) at 24 months. CONCLUSIONS: Care provided by clinicians such as nurses and clinical officers can result in good outcomes for HIV-infected children in primary health care settings in sub-Saharan Africa. Mortality during the first 90 days of therapy is high, pointing to a need for earlier intervention.
Simple adherence assessments to predict virologic failure among HIV-infected adults with discordant immunologic and clinical responses to antiretroviral therapy.
(2008-Aug) Goldman JD; Cantrell RA; Mulenga LB; Tambatamba BC; Reid SE; Levy JW; Limbada M; Taylor A; Saag MS; Vermund SH; Stringer JS; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
We evaluated the association between two antiretroviral therapy (ART) adherence measurements--the medication possession ratio (MPR) and patient self-report--and detectable HIV viremia in the setting of rapid service scale-up in Lusaka, Zambia. Drug adherence and outcomes were assessed in a subset of patients suspected of treatment failure based on discordant clinical and immunologic responses to ART. A total of 913 patients were included in this analysis, with a median time of 744 days (Q1, Q3: 511, 919 days) from ART initiation to viral load (VL) measurement. On aggregate over the period of follow-up, 531 (58%) had optimal adherence (MPR > or =95%), 306 (34%) had suboptimal adherence (MPR 80-94%), and 76 (8%) had poor adherence (MPR <80%). Of the 913 patients, 238 (26%) had VL > or =400 copies/ml when tested. When compared to individuals with optimal adherence, there was increasing risk for virologic failure in those with suboptimal adherence [adjusted relative risk (ARR): 1.3; 95% confidence interval (CI): 1.0, 1.6] and those with poor adherence (ARR: 1.7; 95% CI: 1.3, 2.4) based on MPR. During the antiretroviral treatment course, 676 patients (74%) reported no missed doses. The proportion of patients with virologic failure did not differ significantly among those reporting any missed dose from those reporting perfect adherence (26% vs. 26%, p = 0.97). Among patients with suspected treatment failure, a lower MPR was associated with higher rates of detectable viremia. However, the suboptimal sensitivity and specificity of MPR limit its utility as a sole predictor of virologic failure.
Monitoring effectiveness of programmes to prevent mother-to-child HIV transmission in lower-income countries.
(2008-Jan) Stringer EM; Chi BH; Chintu N; Creek TL; Ekouevi DK; Coetzee D; Tih P; Boulle A; Dabis F; Shaffer N; Wilfert CM; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. eli@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Ambitious goals for paediatric AIDS control have been set by various international bodies, including a 50% reduction in new paediatric infections by 2010. While these goals are clearly appropriate in their scope, the lack of clarity and consensus around how to monitor the effectiveness of programmes to prevent mother-to-child HIV transmission (PMTCT) makes it difficult for policy-makers to mount a coordinated response. In this paper, we develop the case for using population HIV-free child survival as a gold standard metric to measure the effectiveness of PMTCT programmes, and go on to consider multiple study designs and source populations. Finally, we propose a novel community survey-based approach that could be implemented widely throughout the developing world with minor modifications to ongoing Demographic and Health Surveys.
Do targeted HIV programs improve overall care for pregnant women?: Antenatal syphilis management in Zambia before and after implementation of prevention of mother-to-child HIV transmission programs.
(2008-Jan-01) Potter D; Goldenberg RL; Chao A; Sinkala M; Degroot A; Stringer JS; Bulterys M; Vermund SH; Schools of Public Health and Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. dara.potter@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: The implementation of disease-specific research or service programs may have an ancillary beneficial or harmful impact on routine clinical services. METHODS: We reviewed the records of 5801 first visits to 22 antenatal clinics from 1997 to 2004 in Lusaka, Zambia and examined documented syphilis rapid plasma reagin (RPR) screening and syphilis treatment before and after implementation of research and/or service programs in prevention of mother-to-child (PMTCT) HIV transmission. FINDINGS: Compared with before PMTCT program implementation, the prevalence odds ratios (PORs) and 95% confidence intervals (CIs) for documented RPR screening were 0.9 (0.7 to 1.1) after implementation of research, 0.7 (0.6 to 0.8) after service, and 2.5 (2.1 to 3.0) after research and service programs. CONCLUSIONS: Documented RPR screening was improved after implementation of PMTCT research and service were operating simultaneously and not with research or service alone. Health policy makers and researchers should plan explicitly for how the targeted HIV programs, service, and/or research can have a broader primary care impact.
Early lessons from the integration of tuberculosis and HIV services in primary care centers in Lusaka, Zambia.
(2008-Jul) Harris JB; Hatwiinda SM; Randels KM; Chi BH; Kancheya NG; Jham MA; Samungole KV; Tambatamba BC; Cantrell RA; Levy JW; Kimerling ME; Reid SE; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. Jennie.Harris@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Zambia faces overlapping tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics; however, care for co-infected patients often occurs through separate, vertical programs. OBJECTIVE: To establish a program to integrate TB and HIV services in Lusaka primary care centers. METHODS: In collaboration with the Zambian Ministry of Health, TB-HIV integration activities began in December 2005 and were expanded to seven health centers by March 2007. Principal activities included developing staff capacity to manage co-infected patients, implementing HIV testing within TB departments and establishing referral systems between departments. RESULTS: Using a provider-initiated approach, 2053 TB patients were offered HIV testing. Seventy-seven per cent agreed to be tested; 69% of those tested were HIV-infected. Of these, 59% were enrolled in HIV care. The proportion of antiretroviral treatment (ART) program enrollees who were TB-HIV co-infected increased by 38% after program implementation. The median CD4 count among co-infected patients was 161 cells/microl, with 88% eligible for ART. CONCLUSION: Integration of HIV testing and referral services into urban primary care centers identified many co-infected patients and significantly increased the proportion of TB patients among people accessing HIV care. Ongoing challenges include maximizing the number of patients accepting HIV testing and overcoming barriers to enrollment into HIV care.
Extended nevirapine prophylaxis to prevent HIV transmission.
(2008-Jul-26) Stringer JS; Chi BH; University of Alabama at Birmingham, Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia. stringer@cidrz.org