The conduct of Phase I/II HIV vaccine trials internationally necessitates the development of region-specific clinical reference ranges for trial enrolment and participant monitoring. A population based cohort of adults in Kericho, Kenya, a potential vaccine trial site, allowed development of clinical laboratory reference ranges. Lymphocyte immunophenotyping was performed on 1293 HIV seronegative study participants. Hematology and clinical chemistry were performed on up to 1541 cohort enrollees. The ratio of males to females was 1.9∶1. Means, medians and 95% reference ranges were calculated and compared with those from other nations. The median CD4+ T cell count for the group was 810 cells/µl. There were significant gender differences for both red and white blood cell parameters. Kenyan subjects had lower median hemoglobin concentrations (9.5 g/dL; range 6.7–11.1) and neutrophil counts (1850 cells/µl; range 914–4715) compared to North Americans. Kenyan clinical chemistry reference ranges were comparable to those from the USA, with the exception of the upper limits for bilirubin and blood urea nitrogen, which were 2.3-fold higher and 1.5-fold lower, respectively. This study is the first to assess clinical reference ranges for a highland community in Kenya and highlights the need to define clinical laboratory ranges from the national community not only for clinical research but also care and treatment.

In this case series, we examined concomitant risk factors mentioned in reports of torsades de pointes, a rare ventricular arrhythmia, that occurred in association with administration of macrolide antimicrobials (e.g., azithromycin, clarithromycin, dirithromycin, and erythromycin). Increasing age, female sex, and concomitant diseases and drug administration believed to increase risks for torsades de pointes were commonly reported.

Two-hour glucose level was better than fasting glucose level alone at identifying older adults at increased risk of major incident cardiovascular events.

BACKGROUND Peripartum administration of single-dose nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus. METHODS In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death. RESULTS A total of 241 women who had been exposed to single-dose nevirapine began the study treatments (121 received nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P = 0.001). Virologic failure occurred in 37 (28 in the nevirapine group and 9 in the ritonavir-boosted lopinavir group), and 5 died without prior virologic failure (4 in the nevirapine group and 1 in the ritonavir-boosted lopinavir group). The group differences appeared to decrease as the interval between single-dose nevirapine exposure and the start of antiretroviral therapy increased. Retrospective bulk sequencing of baseline plasma samples showed nevirapine resistance in 33 of 239 women tested (14%). Among 500 women without prior exposure to single-dose nevirapine, 34 of 249 in the nevirapine group (14%) and 36 of 251 in the ritonavir-boosted lopinavir group (14%) had virologic failure or died. CONCLUSIONS In women with prior exposure to peripartum single-dose nevirapine (but not in those without prior exposure), ritonavir-boosted lopinavir plus tenofovir–emtricitabine was superior to nevirapine plus tenofovir–emtricitabine for initial antiretroviral therapy. (Funded by the National Institute of Allergy and Infectious Diseases and the National Research Center; ClinicalTrials.gov number, NCT00089505.)

Background Human immunodeficiency virus (HIV) vaccine development remains a global priority. We describe the safety and immunogenicity of a multi-clade DNA vaccine prime with a replication-defective Adenovirus type 5 (rAd5) boost. Methods The vaccine is a 6-plasmid mixture encoding HIV envelope (env) subtypes A, B and C and subtype B gag, pol and nef, and a rAd5 expressing identical genes, with the exception of nef. Three hundred and twenty-four participants were randomized to receive placebo (n=138), a single dose of rAd5 at 1010 (n=24) or 1011 particle units (n=24), or DNA at 0, 1 and 2 months followed by rAd5 at either 1010 (n=114) or 1011 particle units (n=24) boosting at 6 months. Participants were followed for 24 weeks after the final immunization. Results The vaccine was safe and well tolerated. HIV-specific T cell responses were detected in 63% of vaccinees. Pre-existing Ad5 neutralizing antibody titer did not impact the frequency and magnitude of T cell responses in prime-boost recipients, but did impact the response rates in participants receiving rAd5 alone (p=0.037). Conclusion The DNA/rAd5 immunization regimen was safe and induced HIV-1 multi-clade T cell responses, which were not significantly affected by pre-existing rAd5 neutralizing antibody titer.

Background Patients with HIV and low CD4 counts starting antiretroviral therapy (ART) are at high risk for immune reconstitution inflammatory syndrome (IRIS) and death. Methods To investigate the clinical impact of IRIS in adults with HIV and CD4 counts below 100 cells/µL starting ART, we designed an international, prospective, observational study in United States, Thailand, and Kenya. An independent review committee adjudicated IRIS events. We used Cox models to investigate associations between baseline biomarkers, IRIS, immune recovery at week 48, and death by week 48. Results We enrolled 506 participants, 39.3% of whom were women. Median age was 37 years (IQR 31-45) and CD4 T cell count was 29 cells/µL (IQR 11-56). Within 6 months of ART initiation, 97 (19.2%) participants developed IRIS and 31 (6.5%) died. Participants with lower hemoglobin at study start were at higher risk of IRIS (HR 1.2, p=0.004). IRIS was independently associated with increased risk of death even after adjustment for known risk factors (HR 3.2, P=0.031). In addition, being female (P=0.004), having lower BMI (P=0.003), higher WBC (P=0.005) and higher D-dimer levels (P=0.044) were also significantly associated with increased risk of death. Decision tree analysis identified hemoglobin less than 8.5 g/dL as highly predictive of IRIS and CRP>106 µg/ml and BMI < 15.6 kg/m2 as predictive of death . Conclusions For patients with HIV and severe immunosuppression who are initiating ART, baseline low BMI and hemoglobin, and high CRP and D-dimer may be clinically useful predictors of IRIS and death risk.

Treatment had a large, positive impact on the ability of workers to undertake their primary work activity, harvesting tea, in the first year on ART.

Recommendations are provided for interventions to optimize the HIV care environment; increase HIV testing and linkage to care, treatment coverage, retention in care, and viral suppression; and monitor the HIV care continuum.