The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00219557.
Findings All randomised patients were included in the efficacy analyses. Median overall survival was longer with gemcitabine
plus axitinib than with gemcitabine alone (6.9 [95% CI 5.3-10 . 1] months vs 5.6 [3.9-8.8] months). The hazard ratio for survival with gemcitabine plus axitinib versus with gemcitabine alone, adjusted for stratification factors, was 0 . 71 (95% CI 0 . 44-1.13). The most common grade 3 or worse adverse events were GW3965 fatigue (15 [22%] patients in the gemcitabine plus axitinib group vs one [3%] in the gemcitabine alone group), abdominal pain (eight [12%] vs five [16%]), and asthenia
(eight [12%] vs one [3%]).
Interpretation Gemcitabine plus axitinib showed a similar safety profile to gemcitabine alone; the small, non-statistically significant gain in overall survival needs to be assessed in a randomised phase III trial.
Funding Pfizer Inc.”
“Background Across many observational studies, herpes simplex virus type 2 (HSV-2) infection is associated with two-fold to three-fold increased risk for HIV-1 infection. We investigated whether HSV-2 suppression with aciclovir would reduce the risk of HIV-1 acquisition.
Methods PD173074 We undertook a double-blind, randomised, placebo-controlled phase III trial in HIV-negative, HSV-2 seropositive women in Africa and men who have sex with men (MSM) from sites in Peru and the USA. Participants
were randomly assigned by block randomisation to twice daily aciclovir 400 mg (n=1637) or matching placebo (n=1640) for 12-18 months, and were seen monthly for dispensation Bafilomycin A1 manufacturer of study drug, adherence counselling and measurement by pill count and self-reporting, and risk reduction counselling, and every 3 months for genital examination and HIV testing. The primary outcome was HIV-1 acquisition and secondary was incidence of genital ulcers. Analysis was by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00076232.
Findings 3172 participants (1358 women, 1814 MSM) were included in the primary dataset (1581 in aciclovir group, 1591 in control group). The incidence of HIV-1 was 3.9 per 100 person-years in the aciclovir group (75 events in 1935 person-years of follow-up) and 3.3 per 100 person-years in the placebo group (64 events in 1969 person-years of follow-up; hazard ratio 1 . 16 [95% CI 0 . 83-1.62]). Incidence of genital ulcers on examination was reduced by 47% (relative risk 0 . 53 [0.46-0.62]) and HSV-2 positive genital ulcers by 63% (0.37 [0.31-0.45]) in the aciclovir group.