Center for Infectious Diseases Research in Zambia

Lusaka, Zambia

Center for Infectious Diseases Research in Zambia

Lusaka, Zambia
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Tirivayi N.,Maastricht University | Koethe J.R.,Center for Infectious Diseases Research in Zambia | Koethe J.R.,Vanderbilt University
Journal of Public Health (United Kingdom) | Year: 2016

Background: The economic effects of poor immunologic recovery among HIV-infected patients receiving antiretroviral therapy (ART) in sub-Saharan Africa are not well understood. We examined the relationship between the CD4 counts of patients on long-term ARTand employment outcomes in HIV-affected households in Lusaka, Zambia. Methods: Administrative data and a household survey captured information on the clinical records, demographics and employment outcomes of the ART-treated adults and their adult family members (n = 311). Multivariable regression analyses were used to assess relationships between CD4 counts of ART-treated adults and household employment outcomes. Results: Patients with a CD4 count of at least 350 cells/μl were 22 percentage points more likely to be engaged in the labor force (P < 0.05) and worked ∼6 more days per month (P < 0.05) and 9 more hours per week (P = 0.05) compared with patients with a CD4 count <350 cells/μl. Non-patient adults in the HIV-affected household had significantly higher labor participation if the patient's CD4 count was ≥500 compared with <500 cells/μl (P < 0.05), but this was not significant for a CD4 ≥350 versus <350. Conclusion: These findings suggest that interventions to improve or maintain robust immune recovery during ART may confer economic benefits for both HIV-infected individuals and HIV-affected households. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved.


Shankalala P.,University of Zambia | Jacobs C.,University of Zambia | Bosomprah S.,Center for Infectious Diseases Research in Zambia | Bosomprah S.,University of Ghana | And 4 more authors.
Journal of Diabetes and Metabolic Disorders | Year: 2017

Background: Africa has a high prevalence of both Human Immunodeficiency Virus and Non Communicable Diseases (NCDs) but in Zambia there are few data on co-morbid NCDs like Diabetes Mellitus (DM) among HIV-infected individuals. We aimed to identify risk factors for impaired fasting glucose or diabetes among HIV-infected Zambians on long-term Combined Antiretroviral Treatment (cART). Methods: This was a cross sectional study of adult HIV patients in five health facilities of Copperbelt Province in Zambia. HIV/AIDS patients aged 18 years and above, enrolled in care at those health facilities and had been on cART for more than 2 years were included. All patients known to have Diabetes mellitus were excluded from the study. Participants underwent assessment of random blood sugar levels at enrolment and returned the following morning for fasting glucose measured by glucometers. The primary outcome was proportion with impaired fasting glucose or DM. Multivariable logistic regression was used to examine if demographics, time on ART, type of ART regimen, body mass index and baseline CD4 count were predictors of impaired fasting glucose. Results: Overall (n = 270) there were 186 females (69%) and 84 males (31%). The prevalence of impaired fasting blood sugar or diabetes after 8 h of fasting was 15% (95%CI: 11.1, 20.0). Ten percent (26/270) had impaired fasting glucose and 5 % (14/270) had diabetes. Impaired fasting glucose was higher in males than females [AOR = 3.26, (95% CI: 1.15-9.25; p-value = 0.03)]; as well as among patients on second line treatment than those on first line [AOR = 3.87 (95% CI 1.16-12.9); p-value = 0.03]. In contrast those with less likelihood of impaired fasting glucose included patients with a normal BMI (18.5-24.9) than overweight or obese patients [AOR = 0.09 (95% CI 0.03-0.31; p-value < 0.001)]; and participants who had less than 4 diabetes symptoms than those with more than 4 diabetes symptoms [AOR = 0.04 (95% CI 0.02-0.12); p-value < 0.001]. Conclusion: We have found high levels of impaired fasting glucose or diabetes among ART patients compared to what is reported in the general population suggesting missed care and support opportunities associated with metabolic imbalance management. There is thus a need to re-package HIV programming to include integration of diabetes screening as part of the overall care and support strategy. © 2017 The Author(s).


Koethe J.R.,Center for Infectious Diseases Research in Zambia | Koethe J.R.,Vanderbilt University | Marseille E.,Health Strategies International | Giganti M.J.,Center for Infectious Diseases Research in Zambia | And 7 more authors.
Cost Effectiveness and Resource Allocation | Year: 2014

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/m2), moderate (16.00-16.99 kg/m2), and mild (17.00-18.49 kg/m2) 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/m2 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/m2 patients. Among BMI 17.00-18.49 kg/m2 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. © 2014 Koethe et al.; licensee BioMed Central Ltd.


Hosseinipour M.C.,UNC Project | Hosseinipour M.C.,University of North Carolina at Chapel Hill | Bisson G.P.,University of Pennsylvania | Miyahara S.,Harvard University | And 24 more authors.
The Lancet | Year: 2016

Summary Background Mortality within the first 6 months after initiating antiretroviral therapy is common in resource-limited settings and is often due to tuberculosis in patients with advanced HIV disease. Isoniazid preventive therapy is recommended in HIV-positive adults, but subclinical tuberculosis can be difficult to diagnose. We aimed to assess whether empirical tuberculosis treatment would reduce early mortality compared with isoniazid preventive therapy in high-burden settings. Methods We did a multicountry open-label randomised clinical trial comparing empirical tuberculosis therapy with isoniazid preventive therapy in HIV-positive outpatients initiating antiretroviral therapy with CD4 cell counts of less than 50 cells per μL. Participants were recruited from 18 outpatient research clinics in ten countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda). Individuals were screened for tuberculosis using a symptom screen, locally available diagnostics, and the GeneXpert MTB/RIF assay when available before inclusion. Study candidates with confirmed or suspected tuberculosis were excluded. Inclusion criteria were liver function tests 2·5 times the upper limit of normal or less, a creatinine clearance of at least 30 mL/min, and a Karnofsky score of at least 30. Participants were randomly assigned (1:1) to either the empirical group (antiretroviral therapy and empirical tuberculosis therapy) or the isoniazid preventive therapy group (antiretroviral therapy and isoniazid preventive therapy). The primary endpoint was survival (death or unknown status) at 24 weeks after randomisation assessed in the intention-to-treat population. Kaplan-Meier estimates of the primary endpoint across groups were compared by the z-test. All participants were included in the safety analysis of antiretroviral therapy and tuberculosis treatment. This trial is registered with ClinicalTrials.gov, number NCT01380080. Findings Between Oct 31, 2011, and June 9, 2014, we enrolled 850 participants. Of these, we randomly assigned 424 to receive empirical tuberculosis therapy and 426 to the isoniazid preventive therapy group. The median CD4 cell count at baseline was 18 cells per μL (IQR 9-32). At week 24, 22 (5%) participants from each group died or were of unknown status (95% CI 3·5-7·8) for empirical group and for isoniazid preventive therapy (95% CI 3·4-7·8); absolute risk difference of -0·06% (95% CI -3·05 to 2·94). Grade 3 or 4 signs or symptoms occurred in 50 (12%) participants in the empirical group and 46 (11%) participants in the isoniazid preventive therapy group. Grade 3 or 4 laboratory abnormalities occurred in 99 (23%) participants in the empirical group and 97 (23%) participants in the isoniazid preventive therapy group. Interpretation Empirical tuberculosis therapy did not reduce mortality at 24 weeks compared with isoniazid preventive therapy in outpatient adults with advanced HIV disease initiating antiretroviral therapy. The low mortality rate of the trial supports implementation of systematic tuberculosis screening and isoniazid preventive therapy in outpatients with advanced HIV disease. Funding National Institutes of Allergy and Infectious Diseases through the AIDS Clinical Trials Group. © 2016 Elsevier Ltd.


PubMed | University of Witwatersrand, Kenya Medical Research Institute, Stanford University, Frontier Science and 18 more.
Type: Journal Article | Journal: Lancet (London, England) | Year: 2016

Mortality within the first 6 months after initiating antiretroviral therapy is common in resource-limited settings and is often due to tuberculosis in patients with advanced HIV disease. Isoniazid preventive therapy is recommended in HIV-positive adults, but subclinical tuberculosis can be difficult to diagnose. We aimed to assess whether empirical tuberculosis treatment would reduce early mortality compared with isoniazid preventive therapy in high-burden settings.We did a multicountry open-label randomised clinical trial comparing empirical tuberculosis therapy with isoniazid preventive therapy in HIV-positive outpatients initiating antiretroviral therapy with CD4 cell counts of less than 50 cells per L. Participants were recruited from 18 outpatient research clinics in ten countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda). Individuals were screened for tuberculosis using a symptom screen, locally available diagnostics, and the GeneXpert MTB/RIF assay when available before inclusion. Study candidates with confirmed or suspected tuberculosis were excluded. Inclusion criteria were liver function tests 25 times the upper limit of normal or less, a creatinine clearance of at least 30 mL/min, and a Karnofsky score of at least 30. Participants were randomly assigned (1:1) to either the empirical group (antiretroviral therapy and empirical tuberculosis therapy) or the isoniazid preventive therapy group (antiretroviral therapy and isoniazid preventive therapy). The primary endpoint was survival (death or unknown status) at 24 weeks after randomisation assessed in the intention-to-treat population. Kaplan-Meier estimates of the primary endpoint across groups were compared by the z-test. All participants were included in the safety analysis of antiretroviral therapy and tuberculosis treatment. This trial is registered with ClinicalTrials.gov, number NCT01380080.Between Oct 31, 2011, and June 9, 2014, we enrolled 850 participants. Of these, we randomly assigned 424 to receive empirical tuberculosis therapy and 426 to the isoniazid preventive therapy group. The median CD4 cell count at baseline was 18 cells per L (IQR 9-32). At week 24, 22 (5%) participants from each group died or were of unknown status (95% CI 35-78) for empirical group and for isoniazid preventive therapy (95% CI 34-78); absolute risk difference of -006% (95% CI -305 to 294). Grade 3 or 4 signs or symptoms occurred in 50 (12%) participants in the empirical group and 46 (11%) participants in the isoniazid preventive therapy group. Grade 3 or 4 laboratory abnormalities occurred in 99 (23%) participants in the empirical group and 97 (23%) participants in the isoniazid preventive therapy group.Empirical tuberculosis therapy did not reduce mortality at 24 weeks compared with isoniazid preventive therapy in outpatient adults with advanced HIV disease initiating antiretroviral therapy. The low mortality rate of the trial supports implementation of systematic tuberculosis screening and isoniazid preventive therapy in outpatients with advanced HIV disease.National Institutes of Allergy and Infectious Diseases through the AIDS Clinical Trials Group.


PubMed | University of science, Biomedical Primate Research Center, Medical Research Council, Center for Infectious Diseases Research in Zambia and European Vaccine Initiative
Type: Journal Article | Journal: Malaria journal | Year: 2016

The safety and immunogenicity of PfAMA1, adjuvanted with Alhydrogel() was assessed in malaria-experienced Malian adults. The malaria vaccine, PfAMA1-FVO [25-545] is a recombinant protein Pichia pastoris-expressed AMA-1 from Plasmodium falciparum FVO clone adsorbed to Alhydrogel(), the control vaccine was tetanus toxoid produced from formaldehyde detoxified and purified tetanus toxin.A double blind randomized controlled phase 1 study enrolled and followed 40 healthy adults aged 18-55years in Bandiagara, Mali, West Africa, a rural setting with intense seasonal transmission of P. falciparum malaria. Volunteers were randomized to receive either 50g of malaria vaccine or the control vaccine. Three doses of vaccine were given on Days 0, 28 and 56, and participants were followed for 1year. Solicited symptoms were assessed for seven days and unsolicited symptoms for 28days after each vaccination. Serious adverse events were assessed throughout the study. The titres of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed.Commonest local solicited adverse events were the injection site pain and swelling more frequent in the PfAMA1 group. No vaccine related serious adverse events were reported. A significant 3.5-fold increase of anti-AMA-1 IgG antibodies was observed in malaria vaccine recipients four weeks after the third immunization compared to the control group.The PfAMA1 showed a good safety profile. Most adverse events reported were of mild to moderate intensity. In addition, the vaccine induced a significant though short-lived increase in the anti-AMA1 IgG titres. Registered on www.clinicaltrials.gov with the number NCT00431808.


Koethe J.R.,Center for Infectious Diseases Research in Zambia | Koethe J.R.,Vanderbilt University | Blevins M.,Vanderbilt University | Bosire C.,University of Alabama at Birmingham | And 13 more authors.
Public Health Nutrition | Year: 2013

Objective Low BMI is a major risk factor for early mortality among HIV-infected persons starting antiretrovial therapy (ART) in sub-Saharan Africa and the common patient belief that antiretroviral medications produce distressing levels of hunger is a barrier to treatment adherence. We assessed relationships between appetite, dietary intake and treatment outcome 12 weeks after ART initiation among HIV-infected adults with advanced malnutrition and immunosuppression. Design A prospective, observational cohort study. Dietary intake was assessed using a 24 h recall survey. The relationships of appetite, intake and treatment outcome were analysed using time-varying Cox models. Setting A public-sector HIV clinic in Lusaka, Zambia. Subjects One hundred and forty-two HIV-infected adults starting ART with BMI <16 kg/m2 and/or CD4+ lymphocyte count <50 cells/μl. Results Median age, BMI and CD4+ lymphocyte count were 32 years, 16 kg/m2 and 34 cells/μl, respectively. Twenty-five participants (18 %) died before 12 weeks and another thirty-three (23 %) were lost to care. A 500 kJ/d higher energy intake at any time after ART initiation was associated with an approximate 16 % reduction in the hazard of death (adjusted hazard ratio = 0·84; P = 0·01), but the relative contribution of carbohydrate, protein or fat to total energy was not a significant predictor of outcome. Appetite normalized gradually among survivors and hunger was rarely reported. Conclusions Poor early ART outcomes were strikingly high in a cohort of HIV-infected adults with advanced malnutrition and mortality was predicted by lower dietary intake. Intervention trials to promote post-ART intake in this population may benefit survival and are warranted. © 2012 The Authors.


Tirivayi N.,Maastricht University | Koethe J.R.,Center for Infectious Diseases Research in Zambia | Koethe J.R.,Vanderbilt University | Groot W.,Maastricht University
Journal of AIDS and Clinical Research | Year: 2012

Background: There has been limited research to date on the effects of food assistance provided to HIV-infected adults in resource-constrained settings with a high prevalence of malnutrition and chronic food insecurity. We compare antiretroviral therapy (ART) adherence, weight gain, and CD4+ lymphocyte count change among HIVinfected adults enrolled in a clinic-based food assistance program in Lusaka, Zambia versus a control group of non-recipients. Methods: We conducted a cohort study incorporating interviewer-administered surveys and retrospective clinical data to compare ART patients receiving food assistance with a control group of non-recipients. Medication adherence was assessed using pharmacy dispensation records. We use propensity score matching to assess the effect of food assistance on outcome measures. Results: After 6 months, food assistance recipients (n=145) had higher ART adherence compared to nonrecipients (n=147, 98.3% versus 88.8%, respectively; p<0.01), but no significant effects were observed for weight or CD4+ lymphocyte count change. The improvement in adherence rates was greater for participants on ART for less than 230 days, and those with BMI<18.5 kg/m2, a higher HIV disease stage, or a CD4+ lymphocyte count ≤ 350 cells/μl. Conclusions: Promoting optimal medication adherence among persons on ART is relevant to public health and the success of HIV control efforts. The provision of food assistance to HIV-infected adults on ART may have an incentivizing effect which can improve medication adherence, particularly among patients recently initiated on treatment and those with poor nutrition or advanced disease. The effects on body weight and immune reconstitution appear minimal. © 2012 Tirivayi N, et al.


Giarenis I.,King's College | Musonda P.,University of East Anglia | Musonda P.,Center for Infectious Diseases Research In Zambia | Mastoroudes H.,King's College | And 2 more authors.
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2016

Objective Traditionally, urodynamic studies (UDS) have been used to assess lower urinary tract symptoms (LUTS), but their routine use is now discouraged. While urodynamic stress incontinence is strongly associated with the symptom of stress urinary incontinence (SUI) and a positive cough test, there is a weak relationship between symptoms of overactive bladder and detrusor overactivity (DO). The aim of our study was to develop a model to predict DO in women with LUTS. Study design This prospective study included consecutive women with LUTS attending a urodynamic clinic. All women underwent a comprehensive clinical and urodynamic assessment. The effect of each variable on the odds of DO was estimated both by univariate analysis and adjusted analysis using logistic regression. Results 1006 women with LUTS were included in the study with 374 patients (37%) diagnosed with DO. The factors considered to be the best predictors of DO were urgency urinary incontinence, urge rating/void and parity (p-value < 0.01). The absence of SUI, vaginal bulging and previous continence surgery were also good predictors of DO (p-value < 0.01). We have created a prediction model for DO based on our best predictors. In our scoring system, presence of UUI scores 5; mean urge rating/void ≥ 3 scores 3; parity ≥ 2 scores 2; previous continence surgery scores −1; presence of SUI scores −1; and the complaint of vaginal bulging scores −1. If a criterion is absent, then the score is 0 and the total score can vary from a value of −3 to +10. The Receiver Operating Characteristic (ROC) analysis for the overall cut-off points revealed an area under the curve of 0.748 (95%CI 0.741, 0.755). Conclusion This model is able to predict DO more accurately than a symptomatic diagnosis alone, in women with LUTS. The introduction of this scoring system as a screening tool into clinical practice may reduce the need for expensive and invasive tests to diagnose DO, but cannot replace UDS completely. © 2016 Elsevier Ireland Ltd


PubMed | Center for Infectious Diseases Research in Zambia
Type: Journal Article | Journal: Public health nutrition | Year: 2013

Low BMI is a major risk factor for early mortality among HIV-infected persons starting antiretrovial therapy (ART) in sub-Saharan Africa and the common patient belief that antiretroviral medications produce distressing levels of hunger is a barrier to treatment adherence. We assessed relationships between appetite, dietary intake and treatment outcome 12 weeks after ART initiation among HIV-infected adults with advanced malnutrition and immunosuppression.A prospective, observational cohort study. Dietary intake was assessed using a 24 h recall survey. The relationships of appetite, intake and treatment outcome were analysed using time-varying Cox models.A public-sector HIV clinic in Lusaka, Zambia.One hundred and forty-two HIV-infected adults starting ART with BMI <16 kg/m2 and/or CD4+ lymphocyte count <50 cells/l.Median age, BMI and CD4+ lymphocyte count were 32 years, 16 kg/m2 and 34 cells/l, respectively. Twenty-five participants (18%) died before 12 weeks and another thirty-three (23%) were lost to care. A 500 kJ/d higher energy intake at any time after ART initiation was associated with an approximate 16% reduction in the hazard of death (adjusted hazard ratio = 0.84; P = 0.01), but the relative contribution of carbohydrate, protein or fat to total energy was not a significant predictor of outcome. Appetite normalized gradually among survivors and hunger was rarely reported.Poor early ART outcomes were strikingly high in a cohort of HIV-infected adults with advanced malnutrition and mortality was predicted by lower dietary intake. Intervention trials to promote post-ART intake in this population may benefit survival and are warranted.

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