Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials.

BACKGROUND: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1. SETTING: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies. METHODS: Adult participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints. RESULTS: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA <50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm. CONCLUSION: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression.

A review of complications associated with the surgical treatment of vulvar cancer.

OBJECTIVE: The mainstay of treatment for most vulvar malignancies is surgery to the vulva with lymphadenectomy to the inguino-femoral areas, plus radiotherapy or/and chemotherapy for locally advanced, or recurrent disease. Treatment is associated with significant physical, sexual, and psychological morbidity. The high morbidity rate has resulted in a continuing shift in treatment paradigms that focus on treatments that reduce morbidity without compromising cure rates. This paper reviews the complications associated with contemporary surgical treatment for vulva cancer and discusses preventative strategies. METHODS: A review of the English literature was undertaken for articles published between 1965 and August 31, 2012 to identify articles that assessed complications resulting from surgery to the vulva or groins in patients with vulva cancer. Two independent researchers selected and qualitatively analyzed the articles using a predetermined protocol. RESULTS: The heterogeneity of articles and differences in definitions and outcomes made this unsuitable for meta-analysis. Most studies advocated for change in surgical technique to reduce complications associated with inguino-femoral lymphadenectomy and surgery to the vulva, with varying success. The most effective means of preventing complications is by omitting systematic lymph node dissection. This can be achieved safely through sentinel lymph node biopsy. Saphenous vein sparing, VTE prophylaxis, the use of flaps and grafts, and preoperative counseling are additional ways to decrease morbidity. CONCLUSION: Despite technical advances, complications following surgical treatment for vulva cancer remain high. More research, particularly multi centered randomized controlled trials to improve the quality of evidence and studies that focus on complications as an outcome measure and analyze individual surgeon complication rates, are needed. Measures also need to be standardized throughout the gynecologic oncology community to allow for better comparison between studies.

Once weekly fluconazole for antifungal prophylaxis post-liver transplantation.

BACKGROUND: Invasive fungal infections (IFI) remain a significant cause of morbidity and mortality in orthotopic liver transplantation (OLT) recipients. In this retrospective study, the outcomes of a protocol using once weekly fluconazole for 3 months after OLT in low- and high-risk patients were reviewed. METHODS: In total, 221 OLTs were evaluated in the 3-year period after institution of the new protocol to determine the incidence of IFI within 6 months post-OLT. RESULTS: In this cohort, 11 IFIs developed during the 6-month post-transplant period, with the majority being non-albicans Candida. High-risk patients had a greater rate of IFI (16.7% versus 3.4%, P = 0.038) and a significantly longer intensive unit care (ICU) and hospital lengths of stay compared with low-risk patients. Patient and graft survival were similar between the groups. Our patient population appeared to be at low risk for IFI, with 92% of the entire cohort considered low risk. DISCUSSION: Given the low incidence of IFI in the low-risk group and the possibility of such protocol selecting out for fluconazole-resistant fungi, the use of weekly fluconazole for 3 months may not be justifiable in low-risk OLT recipients. Given the increased resource utilization observed with IFI, further examination of a more intensive prophylactic strategy in high-risk patients may be warranted.

Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria.

OBJECTIVE: To identify predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia (VAP) attributed to potentially antibiotic-resistant Gram-negative bacteria (PARGNB) [Pseudomonas aeruginosa, Acinetobacter species, and Stenotrophomonas maltophilia]. DESIGN: A retrospective, single-center, observational cohort study. SETTING: Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital. PATIENTS: Adult patients requiring hospitalization with microbiologically confirmed VAP attributed to PARGNB. INTERVENTIONS: Retrospective data collection from automated hospital, microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: Seventy-six patients with VAP attributed to PARGNB were identified over a 5-year period. Nineteen patients (25.0%) died during hospitalization. Patients receiving their first dose of appropriate antibiotic therapy within 24 h of BAL sampling had a statistically lower 30-day mortality rate compared to patients receiving the first dose of appropriate therapy >24 h after BAL (17.2% vs 50.0%; p = 0.005). VAP due to Acinetobacter species was most often initially treated with an inappropriate antibiotic regimen, followed by S maltophilia and P aeruginosa (66.7% vs 33.3% vs 17.2%; p = 0.017). Overall, total hospitalization costs were statistically similar in patients initially treated with an inappropriate antibiotic regimen compared to an appropriate regimen ($68,597 +/- $55,466 vs $86,644 +/- $64,433; p = 0.390). CONCLUSIONS: These data suggest that inappropriate initial antibiotic therapy of microbiologically confirmed VAP attributed to PARGNB is associated with greater 30-day mortality. High rates of VAP attributed to antibiotic-resistant bacteria (eg, Acinetobacter species) may require changes in the local empiric antibiotic treatment of VAP in order to optimize the prescription of appropriate initial therapy.