Primary resistance to integrase strand transfer inhibitors in Spain using ultrasensitive HIV-1 genotyping.

BACKGROUND: Transmission of resistance mutations to integrase strand transfer inhibitors (INSTIs) in HIV-infected patients may compromise the efficacy of first-line antiretroviral regimens currently recommended worldwide. Continued surveillance of transmitted drug resistance (TDR) is thus warranted. OBJECTIVES: We evaluated the rates and effects on virological outcomes of TDR in a 96 week prospective multicentre cohort study of ART-naive HIV-1-infected subjects initiating INSTI-based ART in Spain between April 2015 and December 2016. METHODS: Pre-ART plasma samples were genotyped for integrase, protease and reverse transcriptase resistance using Sanger population sequencing or MiSeq™ using a ≥ 20% mutant sensitivity cut-off. Those present at 1%-19% of the virus population were considered to be low-frequency variants. RESULTS: From a total of 214 available samples, 173 (80.8%), 210 (98.1%) and 214 (100.0%) were successfully amplified for integrase, reverse transcriptase and protease genes, respectively. Using a Sanger-like cut-off, the overall prevalence of any TDR, INSTI-, NRTI-, NNRTI- and protease inhibitor (PI)-associated mutations was 13.1%, 1.7%, 3.8%, 7.1% and 0.9%, respectively. Only three (1.7%) subjects had INSTI TDR (R263K, E138K and G163R), while minority variants with integrase TDR were detected in 9.6% of subjects. There were no virological failures during 96 weeks of follow-up in subjects harbouring TDR as majority variants. CONCLUSIONS: Transmitted INSTI resistance remains rare in Spain and, to date, is not associated with virological failure to first-line INSTI-based regimens.

Long-term efficacy of 6-month therapy with isoniazid and rifampin compared with isoniazid, rifampin, and pyrazinamide treatment for pleural tuberculosis.

Research into anti-tuberculosis treatment has mainly focused on pulmonary tuberculosis (TB), with few studies on pleural-TB. The aim of the study is to compare the long-term efficacy of a 6-month treatment regimen with isoniazid and rifampicin (6HR) with treatment regimen of isoniazid, rifampicin, and pyrazinamide (6HR2Z) for pleural-TB. A case-control study of 200 HIV-negative patients with pleural-TB prospectively followed in our TB-unit from 1995 to 2018. The primary resistance to isoniazid is < 4% in our geographic area. Pleural-TB diagnosis was based on a positive culture for M. tuberculosis (84 patients), presence of caseating granulomas in pleural biopsy (28), or characteristics of pleural fluid (88). A comparative study of demographic and clinical characteristics between the treatment groups was carried out. Out of the 200 patients followed, (112 males, 88 females; mean age 32.9 ± 18.4 years), 99 patients were treated with 6HR regimen and 101 with 6HR2Z. The groups were comparable, except the 6HR2Z had larger size of pleural effusion. All patients completed the treatment. The group treated with 6HR presented fewer adverse effects (15.3%) than 6HR2Z group (33%), p = 0.005, and lower frequency of severe hepatic toxicity (5% vs 10.9%). Four patients died from causes other than TB during treatment with 6HR2Z, and all other patients were cured during a monitoring period for 8.4 years (IQRs, 3.3-14.3). Six patients in 6HR and 10 in 6HR2Z developed residual pachypleuritis. 6HR is as effective as 6HR2Z treatment for pleural-TB, with fewer adverse effects.