Pamela Njuguna

Reasons for ineligibility in phase 1 and 2A HIV vaccine clinical trials at Kenya AIDS vaccine initiative (KAVI), Kenya.

Background With the persistent challenges towards controlling the HIV epidemic, there is an ongoing need for research into HIV vaccines and drugs. Sub-Saharan African countries - worst affected by the HIV pandemic - have participated in the conduct of clinical trials for HIV vaccines. In Kenya, the Kenya AIDS Vaccine Initiative (KAVI) at the University of Nairobi has conducted HIV vaccine clinical trials since 2001. Methodology Participants were recruited after an extensive informed consent process followed by screening to determine eligibility. Screening included an assessment of risk behavior, medical history and physical examination, and if clinically healthy, laboratory testing. In the absence of locally derived laboratory reference ranges, the ranges used in these trials were derived from populations in the West. Principal findings Two hundred eighty-one participants were screened between 2003 and 2006 for two clinical trials. Of these, 167 (59.4%) met the inclusion/exclusion criteria. Overall, laboratory abnormalities based on the non-indigenous laboratory references used were the most frequent reasons (61.4%) for ineligibility. Medical abnormalities contributed 30.7% of the total reasons for ineligibility. Based on the laboratory reference intervals now developed from East and Southern Africa, those ineligible due to laboratory abnormalities would have been 46.3%. Of the eligible participants, 18.6% declined enrolment. Conclusions Participant recruitment for HIV vaccine clinical trials is a rigorous and time-consuming exercise. Over 61% of the screening exclusions in clinically healthy people were due to laboratory abnormalities. It is essential that laboratory reference ranges generated from local populations for laboratory values be used in the conduct of clinical trials to avoid unnecessary exclusion of willing participants and to avoid over-reporting of adverse events for enrolled participants. Trial registration Protocol IAVI VRC V001 [1]. ClinicalTrials.gov NCT00124007 Protocol IAVI 010 [2] (registration with ClincalTrials.gov is in progress) Protocols IAVI 002 and IAVI 004 are Phase 1 trials only mentioned in introductory paragraphs; details will not be reported. Registration was not required when they were conducted.

The clock is ticking: the rate and timeliness of antiretroviral therapy initiation from the time of treatment eligibility in Kenya.

Understanding the determinants of timely antiretroviral therapy (ART) initiation is useful for HIV programmes intent on developing models of care that reduce delays in treatment initiation while maintaining a high quality of care. We analysed patient‐ and facility‐level determinants of time to ART initiation among patients who initiated ART in Kenya.

Pharmaceutical availability across levels of care: Evidence from facility surveys in Ghana, Kenya, and Uganda

Objective In this study we use facility-level data from nationally representative surveys conducted in Ghana, Kenya, and Uganda to understand pharmaceutical availability within the three countries. Methods In 2012, we conducted a survey to capture information on pharmaceuticals and other facility indicators from over 200 facilities in each country. We analyze data on the availability of pharmaceuticals and quantify its association with various facility-level indicators. We analyze both availability of essential medicines, as defined by the various essential medicine lists (EMLs) of each respective country, and availability of all surveyed pharmaceuticals deemed important for treatment of various high-burden diseases, including those on the EMLs. Results We find that there is heterogeneity with respect to availability across the three countries with Ghana generally having better availability than Uganda and Kenya. To analyze the relationship between facility-level factors and pharmaceutical stock-out we use a binomial regression model. We find that the factors associated with stock-out vary by country, but across all countries both presence of a laboratory at the facility and presence of a vehicle at the facility are significantly associated with reduced stock-out. Conclusion The results of this study highlight the poor availability of essential medicines across these three countries and suggest more needs to be done to strengthen the supply system so that stock remains uninterrupted.

Uptake of WHO Recommendations for First- Line Antiretroviral Therapy in Kenya, Uganda, and Zambia

Introduction Antiretroviral therapy (ART) guidelines were significantly changed by the World Health Organization in 2010. It is largely unknown to what extent these guidelines were adopted into clinical practice. Methods This was a retrospective observational analysis of first-line ART regimens in a sample of health facilities providing ART in Kenya, Uganda, and Zambia between 2007-2008 and 2011-2012. Data were analyzed for changes in regimen over time and assessed for key patient- and facility-level determinants of tenofovir (TDF) utilization in Kenya and Uganda using a mixed effects model. Results Data were obtained from 29,507 patients from 146 facilities. The overall percentage of patients initiated on TDF-based therapy increased between 2007-2008 and 2011-2012 from 3% to 37% in Kenya, 2% to 34% in Uganda, and 64% to 87% in Zambia. A simultaneous decrease in stavudine (d4T) utilization was also noted, but its use was not eliminated, and there remained significant variation in facility prescribing patterns. For patients initiating ART in 2011-2012, we found increased odds of TDF use with more advanced disease at initiation in both Kenya (odds ratio [OR]: 2.78; 95% confidence interval [CI]: 1.73-4.48) and Uganda (OR: 2.15; 95% CI: 1.46-3.17). Having a CD4 test performed at initiation was also a significant predictor in Uganda (OR: 1.43; 95% CI: 1.16-1.76). No facility-level determinants of TDF utilization were seen in Kenya, but private facilities (OR: 2.86; 95% CI: 1.45-5.66) and those employing a doctor (OR: 2.86; 95% CI: 1.48-5.51) were more likely to initiate patients on TDF in Uganda. Discussion d4T-based ART has largely been phased out over the study period. However, significant in-country and cross-country variation exists. Among the most recently initiated patients, those with more advanced disease at initiation were most likely to start TDF-based treatment. No facility-level determinants were consistent across countries to explain the observed facility-level variation.

Trends and Determinants of Antiretroviral Therapy Patient Monitoring Practices in Kenya and Uganda

Introduction Patients receiving antiretroviral therapy (ART) require routine monitoring to track response to treatment and assess for treatment failure. This study aims to identify gaps in monitoring practices in Kenya and Uganda. Methods We conducted a systematic retrospective chart review of adults who initiated ART between 2007 and 2012. We assessed the availability of baseline measurements (CD4 count, weight, and WHO stage) and ongoing CD4 and weight monitoring according to national guidelines in place at the time. Mixed-effects logistic regression models were used to analyze facility and patient factors associated with meeting monitoring guidelines. Results From 2007 to 2012, at least 88% of patients per year in Uganda had a recorded weight at initiation, while in Kenya there was a notable increase from 69% to 90%. Patients with a documented baseline CD4 count increased from 69% to about 80% in both countries. In 2012, 83% and 86% of established patients received the recommended quarterly weight monitoring in Kenya and Uganda, respectively, while semiannual CD4 monitoring was less common (49% in Kenya and 38% in Uganda). Initiating at a more advanced WHO stage was associated with a lower odds of baseline CD4 testing. On-site CD4 analysis capacity was associated with increased odds of CD4 testing at baseline and in the future. Discussion Substantial gaps were noted in ongoing CD4 monitoring of patients on ART. Although guidelines have since changed, limited laboratory capacity is likely to remain a significant issue in monitoring patients on ART, with important implications for ensuring quality care.

What affects patient outcomes? A retrospective cross-country analysis of facility performance in sub-Saharan Africa

Abstract Background The life-saving benefits of antiretroviral therapy (ART) for HIV-infected patients have been well established. However, there continues to be much debate on how best to deliver ART care. In this study, we seek to answer part of this question by examining facility-level determinants of patient outcome. Methods We examined a nationally representative sample of health facilities providing ART in Kenya, Uganda, and Zambia. Facility-level data were collected through an extensive survey that gathered information ranging from finances and management, to services and outputs. Patient-level information was collected from a random sample of charts of patients who were receiving or had received ART. All adult patients who had been on ART between 6 and 60 months at the time of data collection, regardless of outcome, were eligible for inclusion. Descriptive statistics examining patient-level trends at ART initiation over time, as well as logistic regression and survival analyses to assess for facility-level effects on outcome, were performed. Findings We collected data from more than 30 000 patient charts across 138 facilities. Initial findings suggest that patient outcomes are largely driven by patient-level characteristics at the time of ART initiation. Initial CD4 cell count, body-mass index, and WHO clinical staging were all predictive of 12-month and 24-month retention. Conversely, we found no consistent 12-month or 24-month retention trend with regard to facility-level ART programme characteristics such as facility type (hospital vs health clinic), location (urban vs rural), management (private vs public), funding source, number of years the facility has been in operation, leadership type (physician vs nurse), or existence of outreach programmes. Interpretation These findings further support the critical need to expand ART programmes to initiate patients early in the disease process. They also suggest that many aspects of ART care could potentially be carried out safely and effectively at smaller, lower complexity facilities with less-specialised personnel. Funding Bill & Melinda Gates Foundation.

The production and costs of health service across four African countries: Ghana, Kenya, Uganda, and Zambia

Abstract Background Few data exist for the production or costs of health service in developing countries. Consequently, researchers and policy makers have not been able to clearly identify technical or allocative inefficiencies in the provision of care. To remedy this shortcoming, the Institute for Health Metrics and Evaluation, UNICEF, and others have collaborated on de-novo costing exercises across a dozen developing countries. This project has engaged in-country partners to survey over 2300 health facilities. These facilities range from large, referral hospitals to small clinics and pharmacies. Facility-level data are supplemented by centralised information from ministries of health and other national-level financing agents. In most countries, panel data were collected, from 2007 to 2011. Methods Data collection and analysis is ongoing in many countries, but it is complete for a subset, including four African countries: Ghana, Kenya, Uganda, and Zambia. This work will report descriptive values of costs and provision across these countries, as well as results from country-level and cross-country production and cost functions. We particularly focus on quantifying technical inefficiencies in service provision, and on identifying how the degree of those inefficiencies has changed over time. Findings Patterns in expenditure and levels of service provision vary across countries, and these differences are in part explained by each countrys level of economic development. Personnel expenditure is more important in less-developed countries and less-sophisticated facilities, and in general levels of service provision have increased at a faster rate than either personnel counts or expenditure. Interpretation These data and subsequent analyses are critically important to in-country policy makers and international donors. Undoubtedly, the demand for health service will increase in these countries along with population growth and economic wealth. To maintain (let alone improve) current service levels, policy makers must understand the sources and degrees of inefficiency in service provision, and have reliable estimates of the costs of expanding service. This study is the most comprehensive exercise conducted to date to understand these issues across countries. Funding Bill & Melinda Gates Foundation.