Bhatt Km

Safety and immunogenicity of recombinant low-dosage HIV-1 A vaccine candidates vectored by plasmid pTHr DNA or modified vaccinia virus Ankara (MVA) in humans in East Africa

The safety and immunogenicity of plasmid pTHr DNA, modified vaccinia virus Ankara (MVA) human immunodeficiency virus type 1 (HIV-1) vaccine candidates were evaluated in four Phase I clinical trials in Kenya and Uganda. Both vaccines, expressing HIV-1 subtype A gag p24/p17 and a string of CD8 T-cell epitopes (HIVA), were generally safe and well-tolerated. At the dosage levels and intervals tested, the percentage of vaccine recipients with HIV-1-specific cell-mediated immune responses, assessed by a validated ex vivo interferon gamma (IFN-gamma) ELISPOT assay and Cytokine Flow Cytometry (CFC), did not significantly differ from placebo recipients. These trials demonstrated the feasibility of conducting high-quality Phase 1 trials in Africa.

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.

An audit of the informed consent process in postgraduate dissertation studies at the College of Health Sciences, University of Nairobi, Kenya

Background. Informed consent ensures respect for individual autonomy and safeguards against abuses of human participants. However, the high prevalence of poverty, inaccessibility of healthcare services, diseases, social insecurity and low literacy in developing countries such as Kenya increases participants’ vulnerability to research exploitation and abuse. Biomedical and behavioural studies conducted on the vulnerable population in Kenya raise concerns about voluntary participation. Objective. The purpose of this study was to assess the process of obtaining informed consent by postgraduate students in the College of Health Sciences at the University of Nairobi, Kenya. Method. The study was observational, descriptive and quantitative. A convenience sample of 20 postgraduate students at the data collection stage was selected to participate in the study. Each student was observed during four episodes of administering informed consent, totalling 80 episodes of observed student-subject interaction. Data were collected for a period of 6 weeks by means of an observation checklist and analysed using the SPSS version 14 computer package. Descriptive statistics were used to answer the research questions. Results. The main finding was that performance scores were better on the items that had a positive influence on patient participation than on those that would negatively influence patient participation. Conclusions. The consent form was mainly used for the students’ legal protection and not for the patients’ benefit. Recommendation. A further study on a large sample drawn from all the schools of the college is needed to confirm the practice of obtaining informed consent and compare performance in all the schools.