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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.
Browse the collection to explore research covering HIV, TB, maternal and child health, health systems strengthening, and other key public health topics. Articles are frequently harvested from PubMed and other trusted databases.
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Item 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.Item Pregnancy, contraceptive use, and HIV acquisition in HPTN 039: relevance for HIV prevention trials among African women.(2010-Apr) Reid SE; Dai JY; Wang J; Sichalwe BN; Akpomiemie G; Cowan FM; Delany-Moretlwe S; Baeten JM; Hughes JP; Wald A; Celum C; HIV Prevention Research, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. stewart.reid@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: Biomedical HIV prevention trials enroll sexually active women at risk of HIV and often discontinue study product during pregnancy. We assessed risk factors for pregnancy and HIV acquisition, and the effect of pregnancy on time off study drug in HIV Prevention Trials Network 039. METHODS: A total of 1358 HIV negative, herpes simplex virus type 2-seropositive women from South Africa, Zambia, and Zimbabwe were enrolled and followed for up to 18 months. RESULTS: A total of 228 pregnancies occurred; time off study drug due to pregnancy accounted for 4% of woman-years of follow-up among women. Being pregnant was not associated with increased HIV risk (hazard ratio 0.64, 95% confidence interval 0.23-1.80, P = 0.40). However, younger age was associated with increased risk for both pregnancy and HIV. There was no association between condom use as a sole contraceptive and reduced pregnancy incidence; hormonal contraception was not associated with increased HIV risk. Bacterial vaginosis at study entry was associated with increased HIV risk (hazard ratio 2.03, P = 0.02). CONCLUSIONS: Pregnancy resulted in only a small amount of woman-time off study drug. Young women are at high risk for HIV and are an appropriate population for HIV prevention trials but also have higher risk of pregnancy. Condom use was not associated with reduced incidence of pregnancy.Item Early clinical and programmatic outcomes with tenofovir-based antiretroviral therapy in Zambia.(2010-May-01) Chi BH; Mwango A; Giganti M; Mulenga LB; Tambatamba-Chapula B; Reid SE; Bolton-Moore C; Chintu N; Mulenga PL; Stringer EM; Sheneberger R; Mwaba P; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: In July 2007, amid some controversy over cost, Zambia was the first African country to introduce tenofovir (TDF) as a component of first-line antiretroviral therapy (ART) on a wide scale. METHODS: We compared drug substitutions, mortality, and "programmatic failure" among adults starting TDF-, zidovudine (ZDV)-, and stavudine (d4T)-containing ART. Programmatic failure was defined as death, withdrawal, or loss to follow-up. RESULTS: Between July 2007 and January 2009, 10,485 adults initiated ART (66% on TDF, 23% on ZDV, 11% on d4T), with a median follow-up time of 239 (interquartile range 98, 385) days. Those starting TDF were more likely to be male and more likely to have indicators of severe disease at baseline. In adjusted Cox proportional hazards models, ZDV- (adjusted hazard ratio [AHR] = 2.74, 95% confidence interval [CI] = 2.30-3.28) and d4T-based regimens (AHR = 1.92, 95% CI = 1.55-2.38) were associated with higher risk for drug substitution when compared with TDF-based regimens. Similar hazards were noted for overall mortality (ZDV: AHR = 0 .81, 95% CI = 0.62-1.06; d4T: AHR = 1.03, 95% CI = 0.74-1.43) and programmatic failure (ZDV: AHR = 0.99, 95% CI = 0.88-1.11; d4T: AHR = 1.11, 95% CI = 0.96-1.28) when compared with TDF. CONCLUSIONS: TDF is associated with similar clinical and programmatic outcomes as ZDV and d4T but appears to be better tolerated. Although further evaluation is needed, these results are encouraging and support Zambia's policy decision.Item Breastfeeding in HIV-positive women: What can be recommended?(2010) Slater M; Stringer EM; Stringer JS; University of Alabama at Birmingham, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. mackenzieslater@gmail.com; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)Breastfeeding remains a common practice in parts of the world where the burden of HIV is highest and the fewest alternative feeding options exist. The impossible dilemma faced by HIV-positive mothers is whether to breastfeed their infants in keeping with cultural norms but in doing so risk transmitting the virus through breast milk, or to pursue formula feeding, which comes with its own set of risks, including a higher rate of infant mortality from diarrheal illnesses, while reducing transmission of HIV. Treatment of mothers and/or their infants with antiretroviral drugs is a strategy that has been employed for several decades to reduce HIV transmission through pregnancy and delivery, but the effect of these agents when taken during breastfeeding is a newer field of study. In this article we evaluate the latest clinical research, from trials that encourage exclusive breastfeeding to trials of antiretroviral therapy (ART) for either the mother or infant, in an attempt to prevent transmission of HIV through breast milk. Additionally, we discuss research that is in progress, with results anticipated in the next few years that will further shape clinical guidelines and practice. Exclusive breastfeeding is much safer than mixed feeding (the supplementation of breastfeeding with other foods), and should be encouraged even in settings where ART for either the mother or infant is not readily available. The research published regarding maternal treatment with highly active antiretroviral therapy (HAART) during pregnancy and the breastfeeding period has all been non-randomized with relatively little statistical power, but suggests maternal HAART can drastically reduce the risk of transmission of HIV. Infant prophylaxis has been intensively studied in several trials and has been shown to be as effective as maternal treatment with antiretrovirals, reducing the transmission rate after 6 weeks to as low as 1.2%. Research that is in progress will provide us with more answers about the relative contribution of maternal treatment and infant prophylaxis in preventing transmission, and the results of such research may be expected as early as this year through 2013. There is hope that perinatal HIV transmission may be greatly reduced in breastfeeding populations worldwide through a combination of behavioral interventions that encourage exclusive breastfeeding and pharmacologic interventions with antiretrovirals for mothers and/or their infants.Item Implementation of cervical cancer prevention services for HIV-infected women in Zambia: measuring program effectiveness.(2010) Parham GP; Mwanahamuntu MH; Sahasrabuddhe VV; Westfall AO; King KE; Chibwesha C; Pfaendler KS; Mkumba G; Mudenda V; Kapambwe S; Vermund SH; Hicks ML; Stringer JS; Chi BH; University of Cincinnati, OH, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia ; University Teaching Hospital, Lusaka, Zambia.; University of Alabama at Birmingham, AL, USA ; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia ; University Teaching Hospital, Lusaka, Zambia.; Vanderbilt University, TN, USA.; Michigan Cancer Institute, MI, USA.; University of Michigan, MI, USA.; University Teaching Hospital, Lusaka, Zambia.; University of Alabama at Birmingham, AL, USA ; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Vanderbilt University, TN, USA ; National Cancer Institute, MD, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: Cervical cancer kills more women in low-income nations than any other malignancy. A variety of research and demonstration efforts have proven the efficacy and effectiveness of low-cost cervical cancer prevention methods but none in routine program implementation settings of the developing world, particularly in HIV-infected women. METHODS: In our public sector cervical cancer prevention program in Zambia, nurses conduct screening using visual inspection with acetic acid aided by digital cervicography. Women with visible lesions are offered same-visit cryotherapy or referred for histologic evaluation and clinical management. We analyzed clinical outcomes and modeled program effectiveness among HIV-infected women by estimating the total number of cervical cancer deaths prevented through screening and treatment. RESULTS: Between 2006 and 2008, 6572 HIV-infected women were screened, 53.6% (3523) had visible lesions, 58.5% (2062) were eligible for cryotherapy and 41.5% (1461) were referred for histologic evaluation. A total of 75% (1095 out of 1462) of patients who were referred for evaluation complied. Pathology results from 65% (715 out of 1095) of women revealed benign abnormalities in 21% (151), cervical intraepithelial neoplasia (CIN) I in 30% (214), CIN 2/3 in 33% (235) and invasive cervical cancer in 16.1% (115, of which 69% were early stage). Using a conditional probability model, we estimated that our program prevented 142 cervical cancer deaths (high/low range: 238-96) among the 6572 HIV-infected women screened, or one cervical cancer death prevented per 46 (corresponding range: 28-68) HIV-infected women screened. CONCLUSION: Our prevention efforts using setting-appropriate human resources and technology have reduced morbidity and mortality from cervical cancer among HIV-infected women in Zambia. Financial support for implementing cervical cancer prevention programs integrated within HIV/AIDS care programs is warranted. Our prevention model can serve as the implementation platform for future low-cost HPV-based screening methods, and our results may provide the basis for comparison of programmatic effectiveness of future prevention efforts.Item An empirical approach to defining loss to follow-up among patients enrolled in antiretroviral treatment programs.(2010-Apr-15) Chi BH; Cantrell RA; Mwango A; Westfall AO; Mutale W; Limbada M; Mulenga LB; Vermund SH; Stringer JS; Centre for Infectious Disease Research in Zambia, Box 34681, 1275 Lubuto Road, Lusaka, Zambia. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)In many programs providing antiretroviral therapy (ART), clinicians report substantial patient attrition; however, there are no consensus criteria for defining patient loss to follow-up (LTFU). Data on a multisite human immunodeficiency virus (HIV) treatment cohort in Lusaka, Zambia, were used to determine an empirical "days-late" definition of LTFU among patients on ART. Cohort members were classified as either "in care" or LTFU as of December 31, 2007, according to a range of days-late intervals. The authors then looked forward in the database to determine which patients actually returned to care at any point over the following year. The interval that best minimized LTFU misclassification was described as "best-performing." Overall, 33,704 HIV-infected adults on ART were included. Nearly one-third (n = 10,196) were at least 1 day late for an appointment. The best-performing LTFU definition was 56 days after a missed visit, which had a sensitivity of 84.1% (95% confidence interval (CI): 83.2, 85.0), specificity of 97.5% (95% CI: 97.3, 97.7), and misclassification of 5.1% (95% CI: 4.8, 5.3). The 60-day threshold performed similarly well, with only a marginal difference (<0.1%) in misclassification. This analysis suggests that > or =60 days since the last appointment is a reasonable definition of LTFU. Standardization to empirically derived definitions of LTFU will permit more reliable comparisons within and across programs.Item Effectiveness of non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in women previously exposed to a single intrapartum dose of nevirapine: a multi-country, prospective cohort study.(2010-Feb-16) Stringer JS; McConnell MS; Kiarie J; Bolu O; Anekthananon T; Jariyasethpong T; Potter D; Mutsotso W; Borkowf CB; Mbori-Ngacha D; Muiruri P; Ong'ech JO; Zulu I; Njobvu L; Jetsawang B; Pathak S; Bulterys M; Shaffer N; Weidle PJ; University of Alabama at Birmingham Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. stringer@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: Intrapartum and neonatal single-dose nevirapine (NVP) reduces the risk of mother-to-child HIV transmission but also induces viral resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. This drug resistance largely fades over time. We hypothesized that women with a prior single-dose NVP exposure would have no more than a 10% higher cumulative prevalence of failure of their NNRTI-containing antiretroviral therapy (ART) over the first 48 wk of therapy than would women without a prior exposure. METHODS AND FINDINGS: We enrolled 355 NVP-exposed and 523 NVP-unexposed women at two sites in Zambia, one site in Kenya, and two sites in Thailand into a prospective, non-inferiority cohort study and followed them for 48 wk on ART. Those who died, discontinued NNRTI-containing ART, or had a plasma viral load >or=400 copies/ml at either the 24 wk or 48 wk study visits and confirmed on repeat testing were characterized as having failed therapy. Overall, 114 of 355 NVP-exposed women (32.1%) and 132 of 523 NVP-unexposed women (25.2%) met criteria for treatment failure. The difference in failure rates between the exposure groups was 6.9% (95% confidence interval [CI] 0.8%-13.0%). The failure rates of women stratified by our predefined exposure interval categories were as follows: 47 of 116 women in whom less than 6 mo elapsed between exposure and starting ART failed therapy (40%; p<0.001 compared to unexposed women); 25 of 67 women in whom 7-12 mo elapsed between exposure and starting ART failed therapy (37%; p = 0.04 compared to unexposed women); and 42 of 172 women in whom more than 12 mo elapsed between exposure and starting ART failed therapy (24%; p = 0.82 compared to unexposed women). Locally weighted regression analysis also indicated a clear inverse relationship between virologic failure and the exposure interval. CONCLUSIONS: Prior exposure to single-dose NVP was associated with an increased risk of treatment failure; however, this risk seems largely confined to women with a more recent exposure. Women requiring ART within 12 mo of NVP exposure should not be prescribed an NNRTI-containing regimen as first-line therapy.Item A cluster randomized trial of routine HIV-1 viral load monitoring in Zambia: study design, implementation, and baseline cohort characteristics.(2010-Mar-12) Koethe JR; Westfall AO; Luhanga DK; Clark GM; Goldman JD; Mulenga PL; Cantrell RA; Chi BH; Zulu I; Saag MS; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree). METHODOLOGY: Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months. PRINCIPAL FINDINGS: From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites. CONCLUSIONS: A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT00929604.Item 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.Item 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.