Phase 2 double-blind, randomized trial of etravirine versus efavirenz in treatment-naive patients: 48-week results.

BACKGROUND: The Study of Etravirine Neuropsychiatric Symptoms versus Efavirenz (SENSE) trial compared etravirine with efavirenz in treatment-naive patients. The primary endpoint was neuropsychiatric adverse events up to week 12; HIV RNA suppression at week 48 was a secondary endpoint. METHODS: Patients with HIV RNA more than 5000  copies/ml were randomized to etravirine 400  mg once daily (n = 79) or efavirenz (n = 78), plus two nucleoside analogues. HIV RNA less than 50  copies/ml at week 48 was analysed using the time to loss of virological response (TLOVR) algorithm. Drug resistance at treatment failure and safety endpoints were also evaluated. RESULTS: At baseline, the median CD4 cell count was 302  cells/µl and HIV RNA was 4.8 log10  copies/ml. In the intent to treat TLOVR analysis at week 48, 60 of 79 (76%) patients on etravirine versus 58 of 78 (74%) on efavirenz had HIV RNA less than 50  copies/ml. In the on-treatment analysis, 60 of 65 (92%) taking etravirine had HIV RNA les than 50 copies/ml versus 58 of 65 (89%) for efavirenz: etravirine showed noninferior efficacy versus efavirenz in both analyses (P < 0.05). Four patients had virological failure in the etravirine arm: none developed resistance to nucleoside analogues or nonnucleosides. Seven patients had virological failure in the efavirenz arm: three developed treatment-emergent resistance to nucleoside analogues and/or nonnucleosides. At the week 48 visit, the percentage with ongoing neuropsychiatric adverse events was 6.3% for etravirine and 21.5% for efavirenz (P = 0.011). CONCLUSION: First-line treatment with etravirine 400 mg once daily and two nucleoside reverse transcriptase inhibitors (NRTIs) led to similar rates of HIV RNA suppression, compared with efavirenz and two NRTIs. None of the patients with virological failure in the etravirine arm developed resistance to nonnucleosides.

Anal human papillomavirus testing with Digene's hybrid capture 2 using two different sampling methods.

PURPOSE: The incidence of human papillomavirus detection in the anal canal is rising. Efficient anal screening by cytology is hampered because of poor specificity. Human papillomavirus (HPV) testing is proposed in addition to Papanicolaou (Pap) testing for the detection of cervical neoplasia. The purpose of this study was to determine the usefulness of a human papillomavirus-DNA detection test to detect human papillomavirus-associated disease and to compare two different methods of sample collection. METHODS: In 555 patients, anal samples were obtained by using a cervical brush and a Dacron swab to test for high-risk and low-risk human papillomavirus-DNA. Patients positive for human papillomavirus-DNA underwent anoscopy. Biopsies were taken from visible lesions. RESULTS: Low-risk human papillomavirus-DNA was found in 325 of 555 patients (58.6 percent) and high-risk human papillomavirus-DNA in 285 of 555 patients (51.4 percent). Positive results confined to one single test method were higher for Dacron swab sampling (2.3 vs. 4.3 percent for low-risk human papillomavirus, P < 0.0001; 3.1 vs. 4.9 percent for high-risk human papillomavirus, P < 0.001). A positive correlation of relative light units was found for both sampling methods in the total cohort (P < 0.0001) as well as for patients who tested human papillomavirus-positive by both sampling techniques (P < 0.0001). Sampling with Dacron swabs yielded higher relative light units values compared with sampling with cervical brush for low-risk human papillomavirus-DNA and high-risk human papillomavirus-DNA. CONCLUSIONS: Anal screening for human papillomavirus-DNA by hybrid capture 2 is a useful method for detection of human papillomavirus-associated disease. Sample collection using Dacron swabs identifies more human papillomavirus-positive patients, and yields higher relative light unit values than using the cervical brush. Further studies are needed to determine the exact value of hybrid capture 2 in the screening for (pre)cancerous lesions of the anal canal.