Surveillance of Transmitted Antiretroviral Drug Resistance among HIV-1 Infected Women Attending Antenatal Clinics in Chitungwiza, Zimbabwe

The rapid scale-up of highly active antiretroviral therapy (HAART) and use of single dose Nevirapine (SD NVP) for prevention of mother-to-child transmission (pMTCT) have raised fears about the emergence of resistance to the first line antiretroviral drug regimens. A cross-sectional study was conducted to determine the prevalence of primary drug resistance (PDR) in a cohort of young (<25 yrs) HAART-naïve HIV pregnant women attending antenatal clinics in Chitungwiza, Zimbabwe. Whole blood was collected in EDTA for CD4 counts, viral load, serological estimation of duration of infection using the BED Calypte assay and genotyping for drug resistance. Four hundred and seventy-one women, mean age 21 years; SD: 2.1 were enrolled into the study between 2006 and 2007. Their median CD4 count was 371cells/µL; IQR: 255–511 cells/µL. Two hundred and thirty-six samples were genotyped for drug resistance. Based on the BED assay, 27% were recently infected (RI) whilst 73% had long-term infection (LTI). Median CD4 count was higher (p<0.05) in RI than in women with LTI. Only 2 women had drug resistance mutations; protease I85V and reverse transcriptase Y181C. Prevalence of PDR in Chitungwiza, 4 years after commencement of the national ART program remained below WHO threshold limit (5%). Frequency of recent infection BED testing is consistent with high HIV acquisition during pregnancy. With the scale-up of long-term ART programs, maintenance of proper prescribing practices, continuous monitoring of patients and reinforcement of adherence may prevent the acquisition and transmission of PDR

Cluster randomized trials of prescription medicines or prescribing policy:public and general practitioner opinions in Scotland

AIMS: To understand public and general practitioner (GP) opinion on the acceptability of randomized policy design (RPD) studies (cluster randomized trials) of prescription medicines in Scotland. METHODS: We surveyed public opinion on the concept of RPD studies in a sample of 1040 adults to determine acceptability and understand how people feel when changes are made to their medicines. We also surveyed GPs (n = 1034) about the concept of RPD studies as a tool for improving understanding of comparative effectiveness and safety of medicines in the 'usual care' setting. RESULTS: Thirty per cent of people would be happy to receive a letter about randomized policy changes to their therapy, 31% would not mind or had no opinion and 39% would be unhappy. This view was sensitive to the reason for change; effectiveness and safety reasons were most acceptable (96%) and cost saving least acceptable (39%). Only 19% thought randomized policy change was not an acceptable method of determining the best treatments. Eighty-one per cent of respondents were willing for their medical data to be followed up to compare drug treatments (further 10% undecided). Participants reporting long-term medical conditions and those reporting previous changes to drug therapy were more in favour of RPD studies than other participants. Thirty-three per cent (n = 341) of GPs responded to our survey. Of these, 45% were in favour of RPD studies, 19% were undecided and 36% not in favour. CONCLUSIONS: The public in Scotland is broadly supportive of the concept of randomized policy design studies of medicines, while there is a spread of opinion among GPs

Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays

Naturally occurring mutations in HIV-1-infected patients have important implications for therapy and the outcome of clinical studies. However, little is known about the prevalence of mutations that confer resistance to HIV-1 protease inhibitors in isolates derived from patients naive for such inhibitors. In the first clinical application of high-density oligonucleotide array sequencing, the sequences of 167 viral isolates from 102 patients have been determined. The DNA sequence of USA HIV-1 clade B proteases was found to be extremely variable and 47.5% of the 99 amino acid positions varied. This level of amino acid diversity is greater than that previously known for all worldwide HIV-1 clades combined (40%). Many of the amino acid changes that are known to contribute to drug resistance occurred as natural polymorphisms in isolates from patients who had never received protease inhibitors