Effect of Baseline Renal Function on Tenofovir-Containing Antiretroviral Therapy Outcomes in Zambia

In this large cohort of human immunodeficiency virus-infected patients receiving first-line antiretroviral therapy in Zambia, individuals who started a tenofovir-containing regimen despite baseline renal dysfunction showed comparable mortality and renal function improvement to those not receiving tenofovi

Universal Definition of Loss to Follow-Up in HIV Treatment Programs: A Statistical Analysis of 111 Facilities in Africa, Asia, and Latin America

Background: Although patient attrition is recognized as a threat to the long-term success of antiretroviral therapy programs worldwide, there is no universal definition for classifying patients as lost to follow-up (LTFU). We analyzed data from health facilities across Africa, Asia, and Latin America to empirically determine a standard LTFU definition. Methods and Findings: At a set ''status classification'' date, patients were categorized as either ''active'' or ''LTFU'' according to different intervals from time of last clinic encounter. For each threshold, we looked forward 365 d to assess the performance and accuracy of this initial classification. The best-performing definition for LTFU had the lowest proportion of patients misclassified as active or LTFU. Observational data from 111 health facilities - representing 180,718 patients from 19 countries - were included in this study. In the primary analysis, for which data from all facilities were pooled, an interval of 180 d (95% confidence interval [CI]: 173–181 d) since last patient encounter resulted in the fewest misclassifications (7.7%, 95% CI: 7.6%–7.8%). A secondary analysis that gave equal weight to cohorts and to regions generated a similar result (175 d); however, an alternate approach that used inverse weighting for cohorts based on variance and equal weighting for regions produced a slightly lower summary measure (150 d). When examined at the facility level, the best-performing definition varied from 58 to 383 d (mean = 150 d), but when a standard definition of 180 d was applied to each facility, only slight increases in misclassification (mean = 1.2%, 95% CI: 1.0%–1.5%) were observed. Using this definition, the proportion of patients classified as LTFU by facility ranged from 3.1% to 45.1% (mean = 19.9%, 95% CI: 19.1%–21.7%). Conclusions: Based on this evaluation, we recommend the adoption of $180 d since the last clinic visit as a standard LTFU definition. Such standardization is an important step to understanding the reasons that underlie patient attrition and establishing more reliable and comparable program evaluation worldwide

Nutrition and inflammation serum biomarkers are associated with 12-week mortality among malnourished adults initiating antiretroviral therapy in Zambia

<p>Abstract</p> <p>Background</p> <p>A low body mass index (BMI) at antiretroviral therapy (ART) initiation is a strong predictor of mortality among HIV-infected adults in resource-constrained settings. The relationship between nutrition and inflammation-related serum biomarkers and early treatment outcomes (e.g., less than 90 days) in this population is not well described.</p> <p>Methods</p> <p>An observational cohort of 142 HIV-infected adults in Lusaka, Zambia, with BMI under 16 kg/m²or CD4⁺lymphocyte counts of less than 50 cells/mm³, or both, was followed prospectively during the first 12 weeks of ART. Baseline and serial post-treatment phosphate, albumin, ferritin and highly sensitive C-reactive protein (hsCRP) serum levels were measured. The primary outcome was mortality.</p> <p>Results</p> <p>Lower baseline phosphate and albumin serum levels, and higher ferritin and hsCRP, were significantly associated with mortality prior to 12 weeks (p < 0.05 for all comparisons), independent of known risk factors for early ART-associated mortality in sub-Saharan Africa. The time-dependent interval change in albumin was associated with mortality after adjusting for the baseline value (AHR 0.62 [0.43, 0.89] per 5 g/L increase), but changes in the other biomarkers were not.</p> <p>Conclusions</p> <p>The predictive value of serum biomarkers for early mortality in a cohort of adults with malnutrition and advanced HIV in a resource-constrained setting was primarily driven by pre-treatment values, rather than post-ART changes. Interventions to promote earlier HIV diagnosis and treatment, address nutritional deficiencies, and identify the etiologies of increased systemic inflammation may improve ART outcomes in this vulnerable population.</p

Adherence Support Workers: A Way to Address Human Resource Constraints in Antiretroviral Treatment Programs in the Public Health Setting in Zambia

BACKGROUND: In order to address staff shortages and improve adherence counseling for people on antiretroviral therapy (ART), the Zambia Prevention, Care and Treatment Partnership (ZPCT) developed an innovative strategy of training community volunteers to provide adherence support at the health facility and community levels. The objective of this study was to assess the effectiveness of these 'adherence support workers' (ASWs) in adherence counseling, treatment retention and addressing inadequate human resources at health facilities.METHODOLOGY/PRINCIPAL FINDINGS: The study used quantitative and qualitative research techniques at five selected ART sites in four provinces in Zambia. Five hundred patients on ART were interviewed using a structured questionnaire to compare the quality of adherence counseling before and after the ASW scheme was introduced at the selected sites and between ASWs and HCWs after the introduction of ASWs. In addition, 3,903 and 4,972 electronic records of all new patients accessing antiretroviral therapy for the time period of 12 months before and 12 months after the introduction of ASWs respectively, were analyzed to assess loss to follow-up rates. Two focus group discussions with ASWs and health care workers (HCWs) were conducted in each clinic. Key informant interviews in the ART clinics were also conducted. There was a marked shift of workload from HCWs to ASWs without any compromise in the quality of counseling. Quality of adherence counseling by ASWs was comparable to HCWs after their introduction. The findings suggest that the deployment of ASWs helped reduce waiting times for adherence counseling. Loss to follow-up rates of new clients declined from 15% to 0% after the deployment of ASWs.CONCLUSION: Adherence counseling tasks can be shifted to lay cadres like ASWs without compromising the quality of counseling. Follow-up of clients by ASWs within the community is necessary to improve retention of clients on ART

Estimating Loss to Follow-Up in HIV-Infected Patients on Antiretroviral Therapy: The Effect of the Competing Risk of Death in Zambia and Switzerland

BACKGROUND: Loss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland. METHODS AND FINDINGS: HIV-infected patients aged ≥18 years who started ART 2004-2008 in observational cohorts in Zambia and Switzerland were included. We compared standard Kaplan-Meier curves with CR cumulative incidence. We calculated hazard ratios for LTFU across CD4 cell count strata using cause-specific Cox models, or Fine and Gray subdistribution models, adjusting for age, gender, body mass index and clinical stage. 89,339 patients from Zambia and 1,860 patients from Switzerland were included. 12,237 patients (13.7%) in Zambia and 129 patients (6.9%) in Switzerland were LTFU and 8,498 (9.5%) and 29 patients (1.6%), respectively, died. In Zambia, the probability of LTFU was overestimated in Kaplan-Meier curves: estimates at 3.5 years were 29.3% for patients starting ART with CD4 cells <100 cells/µl and 15.4% among patients starting with ≥350 cells/µL. The estimates from CR cumulative incidence were 22.9% and 13.6%, respectively. Little difference was found between naïve and CR analyses in Switzerland since only few patients died. The results from Cox and Fine and Gray models were similar: in Zambia the risk of loss to follow-up and death increased with decreasing CD4 counts at the start of ART, whereas in Switzerland there was a trend in the opposite direction, with patients with higher CD4 cell counts more likely to be lost to follow-up. CONCLUSIONS: In ART programmes in low-income settings the competing risk of death can substantially bias standard analyses of LTFU. The CD4 cell count and other prognostic factors may be differentially associated with LTFU in low-income and high-income settings

Disclosure to HIV-seropositive children in rural Zambia

Abstract Background Care of children living with HIV comprises various issues, some considered challenging. One of the challenging areas is the serostatus disclosure to HIV-positive children. This study describes the current situation of HIV disclosure among rural children in Zambia and examines the socio-demographic factors promoting disclosure. Methods We used a mixed method approach applying both quantitative and qualitative methods to obtain comprehensive picture of HIV serostatus disclosure for children. Data were collected in Mumbwa district, Zambia (2010–2012), included 57 clinical records of children older than 5 years old. We examined children’s age, gender, and cohabitation status with their parents, caregivers’ level of education and income, and the relation between children and caregivers. Logistic regression model was applied to examine associations between disclosure and socio-demographic characteristics. Semi-structured interviews with 50 caregivers and 22 HIV-positive children were conducted to qualitatively investigate attitude towards disclosure and support needed. Results Full disclosure was completed in 17 out of 57 (29.8%) patients. Median ages of patients in disclosed group and non-disclosed group were 10 and 9, respectively (IQR 8.0–13.0, 7.0–11.25). In univariate analyses, older age and male gender has positive relation to the completion of serostatus disclosure. In logistic regression models, cohabitation status with patients’ mothers showed positive correlation to the completion of serostatus disclosure. In the interviews with caregivers, all caregivers said that disclosure of serostatus is a necessary process and good for their children, while actual serostatus disclosure rate was low. Conclusion Serostatus disclosure to HIV-seropositive children is not prevalent in Rural Zambia. Although further researches would be desirable, increased support to caregivers would be beneficial

Health outcomes and cost impact of the new WHO 2013 guidelines on prevention of mother-to-child transmission of HIV in Zambia.

BackgroundCountries are currently progressing towards the elimination of new paediatric HIV infections by 2015. WHO published new consolidated guidelines in June 2013, which now recommend either 'Antiretroviral drugs (ARVs) for women living with HIV during pregnancy and breastfeeding (Option B)' or 'Lifelong antiretroviral therapy (ART) for all pregnant and breastfeeding women living with HIV (Option B+)', while de facto phasing out Option A. This study examined health outcomes and cost impact of the shift to WHO 2013 recommendations in Zambia.MethodsA decision analytic model was developed based on the national health system perspective. Estimated risk and number of cases of HIV transmission to infants and to serodiscordant partners, and proportions of HIV-infected pregnant women with CD4 count of ≤350 cells/mm3 to initiate ART were compared between 2010 Option A and the 2013 recommendations. Total costs of prevention of mother-to-child transmission of HIV (PMTCT) services per annual cohort of pregnant women, incremental cost-effectiveness ratio (ICER) per infection averted and quality-adjusted life-year (QALY) gained were examined.ResultsOur analysis suggested that the shift from 2010 Option A to the 2013 guidelines would result in a 33% reduction of the risk of HIV transmission among exposed infants. The risk of transmission to serodiscordant partners for a period of 24 months would be reduced by 72% with 'ARVs during pregnancy and breastfeeding' and further reduced by 15% with 'Lifelong ART'. The probability of HIV-infected pregnant women to initiate ART would increase by 80%. It was also suggested that while the shift would generate higher PMTCT costs, it would be cost-saving in the long term as it spares future treatment costs by preventing infections in infants and partners.ConclusionThe shift to the WHO 2013 guidelines in Zambia would positively impact health of family and save future costs related to care and treatment

Health outcomes - HIV infections among exposed infants and serodiscordant partners.

<p>Health outcomes - HIV infections among exposed infants and serodiscordant partners.</p

Cost related outcomes - Base-case analysis.

a<p>For a period of 24 months (from 14 weeks of pregnancy to 18 months after delivery) per annual cohort of 600,000 pregnant women.</p>b<p>Based on the costs of PMTCT programme.</p