Transmission risk behaviour at enrolment in participants in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

OBJECTIVES: A proportion of HIV-positive people have condomless sex. Antiretroviral treatment (ART) reduces infectiousness, but a substantial proportion of HIV-diagnosed people are not yet on ART. We describe baseline self-reported risk behaviours in ART-naïve Strategic Timing of AntiRetroviral Treatment (START) trial participants. METHODS: All START participants completed a risk behaviour questionnaire. Data were collected on sociodemographics, lifestyle factors, health and wellbeing status and clinical status. Recent sexual behaviour and HIV transmission beliefs in the context of ART were also assessed. The primary interest was in condomless sex with serodifferent partners (CLS-D) in the past two months. RESULTS: A total of 4601 of 4685 HIV-positive participants (98%) completed the questionnaire [2559 men who have sex with men (MSM), 803 heterosexual men and 1239 women]. Region of recruitment was Europe/Israel, 33%; South America/Mexico, 25%; Africa, 22%; other, 21%. Median age was 36 years [interquartile range (IQR) 29, 44 years]. Forty-five per cent reported white ethnicity and 31% black ethnicity. Two per cent had HIV viral load < 50 HIV-1 RNA copies/mL. Seventeen per cent (767 of 4601) reported CLS-D; 20% of MSM compared with 10% of heterosexual men and 14% of women. MSM were also more likely to report multiple CLS-D partners. Possible risk limitation measures (reported by more than half of those who had CLS-D) were seropositioning (receptive anal CLS-D only) or withdrawal (insertive anal CLS-D always without ejaculation). CLS-D was more commonly reported by participants from South America/Mexico and North America compared with Europe; among heterosexual men and women CLS-D was also more commonly reported among participants from Africa compared with Europe. Knowledge of ART impact on transmission risk was low. CONCLUSIONS : A substantial minority recruited to the START study reported CLS-D at baseline. CLS-D reporting was higher in MSM than eterosexuals and varied significantly according to region of recruitment. A substantial proportion of MSM reporting CLS-D appear to take transmission risk limitation measures

Efficacy and safety of sequential intravenous/oral moxifloxacin vs intravenous/oral amoxicillin/clavulanate for complicated skin and skin structure infections.

BACKGROUND: Complicated skin and skin structure infections (cSSSIs) are an important healthcare concern worldwide, as they can be life-threatening and challenging to treat. cSSSIs are normally managed using a combination of surgical intervention and prompt antibiotic use. New therapeutic options, including novel antibiotics, are required to improve outcomes in terms of duration of illness and to reduce the consumption of healthcare resources. METHODS: This was a prospective, randomized, open-label, parallel-group, multinational clinical study comparing sequential intravenous/oral (iv/po) moxifloxacin, 400 mg once daily, and iv amoxicillin/clavulanate, 1,000 mg/ 200 mg three times daily followed by po amoxicillin/ clavulanate, 500 mg/125 mg three times daily, for 7-21 days in hospitalized patients. RESULTS: A total of 804 patients were enrolled (mean age 51.8 years). The most common clinical diagnosis was complicated erysipelas (32.1% moxifloxacin; 30.0% amoxicillin/ clavulanate) and major abscess (31.1% moxifloxacin; 29.3% amoxicillin/clavulanate). Overall clinical success rates at the test-of-cure (TOC) visit (14-28 days post-treatment) for the per-protocol population (primary efficacy variable) were 80.6% (254/315) for patients in the moxifloxacin group and 84.5% (268/317) for those receiving amoxicillin/clavulanate (95% confidence interval [CI] -9.41, 2.18). Similar results were obtained for the intention-to-treat population (95% CI -7.56, 4.31). In both treatment groups, the highest clinical success rates were recorded for patients with complicated erysipelas, major abscess, surgical wound infection, and cellulitis. The lowest clinical cure rates were reported for diabetic foot infection and necrotizing fasciitis. In the microbiologically evaluable population, the bacteriological success rate (eradication and presumed eradication) was 76.0% (127/ 167) in the moxifloxacin group and 81.4% (140/172) in the amoxicillin/clavulanate group (95% CI -12.96, 4.41). Staphylococcus aureus (137 isolates) and Escherichia coli (50 isolates) were the most frequently isolated skin pathogens. Adverse event rates were comparable between treatment groups. CONCLUSIONS: Treatment with sequential iv/po moxifloxacin monotherapy once daily is clinically comparable to that with iv/po amoxicillin/clavulanate three times daily in the management of cSSSIs. Moxifloxacin's simple dose regimen offers an advantage over amoxicillin/clavulanate and represents a valuable addition to current antibiotic regimens used in the treatment of cSSSIs.