Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are expected to be widely adopted globally, requiring surveillance of resistance emergence and transmission. OBJECTIVES: We therefore sought to develop a standardized list of INSTI-resistance mutations suitable for the surveillance of transmitted INSTI resistance. METHODS: To characterize the suitability of the INSTI-resistance mutations for transmitted HIV-1 drug resistance (TDR) surveillance, we classified them according to their presence on published expert lists, conservation in INSTI-naive persons, frequency in INSTI-treated persons and contribution to reduced in vitro susceptibility. Mutation prevalences were determined using integrase sequences from 17302 INSTI-naive and 2450 INSTI-treated persons; 53.3% of the INSTI-naive sequences and 20.0% of INSTI-treated sequences were from non-B subtypes. Approximately 10% of sequences were from persons who received dolutegravir alone or a first-generation INSTI followed by dolutegravir. RESULTS: Fifty-nine previously recognized (or established) INSTI-resistance mutations were present on one or more of four published expert lists. They were classified into three main non-overlapping groups: 29 relatively common non-polymorphic mutations, occurring in five or more individuals and significantly selected by INSTI treatment; 8 polymorphic mutations; and 22 rare mutations. Among the 29 relatively common INSTI-selected mutations, 24 emerged as candidates for inclusion on a list of INSTI surveillance drug-resistance mutations: T66A/I/K, E92G/Q, G118R, F121Y, E138A/K/T, G140A/C/S, Y143C/H/R/S, S147G, Q148H/R/K, N155H, S230R and R263K. CONCLUSIONS: A set of 24 non-polymorphic INSTI-selected mutations is likely to be useful for quantifying INSTI-associated TDR. This list may require updating as more sequences become available from INSTI-experienced persons infected with HIV-1 non-subtype B viruses and/or receiving dolutegravir.

Can morbidly obese patients with reflux be offered laparoscopic sleeve gastrectomy? A case report of 40 patients.

BACKGROUND: The incidence of reflux in obesity can reach greater than 35%. Most surgeons recommend Roux-en-y gastric bypass to patients with pre-existing reflux. One alternative to Roux-en-y gastric bypass is the addition of anterior fundoplication (AF) with posterior crural approximation (pCA) to laparoscopic sleeve gastrectomy (LSG) in patients with documented reflux. METHODS: Between February 2011 and April 2013 we reviewed data from the bariatric registry on weight loss, resolution of symptoms, and quality of life presurgery and postsurgery for all patients who consented to participate in the registry and underwent LSG with AF/pCA. RESULTS: Forty patients met inclusion criteria; 78% (31) were female. The mean initial weight was 298 ± 64 lbs. with mean BMI of 49 ± 8 kg/m(2). The mean DeMeester score was 36 ± 27 (normal <14.7). Nine (22.5%) patients had esophagitis. Thirty-six (90%) patients had hiatal hernia. There were no intraoperative complications. The mean operative time was 84 ± 20 minutes and the mean hospital stay was 1.6 ± .9 days. Postoperative complications included 1 fluid collection, 1 narrowing, 4 admissions for nausea and dehydration, 1 for pancreatitis, and 1 for deep vein thrombosis . Thirty-eight (95%) patients had immediate resolution of reflux, whereas 2 (5%) patients complained of worsening symptoms. On short-term follow-up of 24 ± 6 months, 55% of patients responded to the gastroesophageal reflux disease-health related quality of life questionnaire with improvement in their median score from 31/75 interquartile range (IQR 25) preoperatively to 0/75 (IQR 6.5) postoperatively (P < .0001). Their %excess body mass index loss was 69 ± 27%. CONCLUSIONS: Morbidly obese patients with documented reflux can be offered LSG with the addition of AF/pCA.

Laparoscopic Management of Severe Reflux After Sleeve Gastrectomy, in Selected Patients, Without Conversion to Roux-en-Y Gastric Bypass.

BACKGROUND: Treatment of severe reflux after laparoscopic sleeve gastrectomy (LSG) may require conversion to Roux-en-Y gastric bypass (RYGB). We conducted a pilot study to evaluate the feasibility and effectiveness of performing laparoscopic anterior fundoplication with posterior crura approximation (LAF/pCA), in selected patients, to correct the reflux without conversion to RYGB. PATIENTS AND METHODS: From October 2012 to April 2013, 6 patients with confirmed severe de novo reflux after LSG were treated with LAF/pCA. RESULTS: All patients were females with a mean age of 41.5±14.2 years. All patients had lost weight after initial LSG. The percentage excess body mass index (BMI) loss (%EBL) was 61.2±33.2%. The mean time from the initial LSG to LAF/pCA was 33.2±12.5 months. Four patients had reduction of gastric fundus size. One patient required resleeving. Reflux resolved immediately in all patients with a follow-up of 18.5±2.7 months. All patients continued to lose weight, with %EBL reaching 75.5±22.9% and a mean BMI of 32±7.3 kg/m(2). CONCLUSIONS: LAF/pCA with reduction of gastric fundus size, when needed, may be considered an alternative option to correct severe reflux after LSG in selected patients.