Transmitted antiretroviral drug resistance to Integrase Strand Transfer Inhibitors class in São Paulo metropolitan area, Brazil.

Objectives A newer Integrase Strand Transfer Inhibitor (INSTI) cabotegravir was recently approved for both therapy and prophylaxis and can play an essential role in the fight against AIDS. It shares similar resistance profile to dolutegravir, the cornerstone of Brazilian antiretroviral treatment (ARV), with about 600 thousand people living with HIV in Brazil currently on regimens that contain this INSTI. Health services in the São Paulo metropolitan area are responsible to a large proportion of ARV dispensation in the country. Estimating Transmitted Drug Resistance Mutation (TDRM) in the area before cabotegravir introduction may provide a useful baseline information. Methods Partial HIV-1 pol gene was sequenced (Sanger) from 192 newly diagnosed individuals from São Paulo and nearby cities (2020 to March 2023) at integrase, with 85 also at protease/reverse transcriptase regions. Retrotranscribed plasma RNA, amplified with nested PCR, was edited (Recall or Sequencher) and analyzed at Rega and Stanford db. Results Surveillance DRM (SDRM) to INSTI class was detected in three cases (1.6% CI95% 0.5%-5%), two E138K and one R263K, with 7.8% (CI95% 5%-13%) with resistance mutations (major or accessory). SDRM for NRTI, NNRTI, and PI classes were identified in 7 (8.2% CI95% 4%-16%) cases. Subtype B predominated (69%), followed by subtype C (16%), now the second most prevalent infection in this area. Among 131 patients treated for over six months, 92% were virally suppressed below 200 copies/mL, with low TCD4 counts independently associated to failure. Conclusions SDRM to INSTI class is rare in the area. Intermediate rates of transmitted resistance to other ARV classes are comparable to previous estimates. Viral suppression rates may depend on TCD4 counts, another negative impact of late diagnosis in care that deserves more attention.

Long-term virological effectiveness with darunavir/ritonavir-based salvage therapy in people living with HIV/AIDS from São Paulo, Brazil.

Even though darunavir/ritonavir (DRV/r) has high potency and a greater genetic barrier, there are few studies on the long-term effectiveness of DRV/r-based salvage therapy in people living with HIV (PLWH) in low and middle-income countries. This retrospective cohort study, from São Paulo, Brazil, included ART-experienced PLWH aged ≥18 years with virological failure (VF) who had started DRV/r plus an optimized background regimen (OBR) between 2008 and 2012. The proportion of patients with viral load (VL) <50 copies/mL, the improved mean CD4+ T cell count and the factors associated with VF during the 144-week follow-up were assessed. The study included 173 patients with the following characteristics [median (interquartile range)]: age 48 (42 -53) years; CD4+ T cell count, 229 (89 -376) cells/mm3; VL, 4.26 (3.70 -4.74) log10; 6 (4 -7) previous regimens; and 100 (38 -156) months of VF. After 144 weeks, 129 (75%) patients had VL< 50 copies/mL and a mean increase in the CD4+ T cell count of 190 cells/mm3. VL>100,000 copies/mL and poor adherence were associated with VF. DRV/r plus an OBR showed high long-term virological suppression and immunological recovery. VL>100,000 copies/mL and poor adherence were associated with VF at 144 weeks.

Major drug resistance mutations to HIV-1 protease inhibitors (PI) among patients exposed to PI class failing antiretroviral therapy in São Paulo State, Brazil.

BACKGROUND: Protease inhibitors (PI) are especially important in salvage therapy. Previous treatment failure with a PI containing regimen may elicit resistance mutations, reducing PI susceptibility and limiting treatment options. The aim of this study was to describe major PI mutations among patients exposed to at least one PI to evaluate predictors of mutation emergence and the impact of subtypes on resistance. METHODOLOGY: Partial HIV-1 pol sequences (Sanger Sequencing) from patients exposed to PI with virological failure were genotyped from January 2014 to December 2017. Drug resistance mutations (DRM), antiretroviral susceptibility (GSS) and subtypes, along clinical and laboratory parameters, were evaluated using logistic regression to access the predictors of mutation emergence. RESULTS: In 27.5% (466/1696) of the cases at least one major PI mutations was identified, most commonly M46 (14.7%), V82 (13.8%) and I54 (13.3%). Mutations to NRTI and NNRTI were observed in 69.6% and 59.9%, respectively, of the 1696 sequences. Full activity to darunavir was predicted in 88% (1496/1696), but was only 57% among those with at least one PI-DRM. Subtype C sequences had less major PI-DRMs (10%, 9/87) compared to B (28%, 338/1216) or F (35%, 58/168) (p <0.001) but adjusted analysis suggested that this association is not independent from a shorter treatment time and fewer regimens (OR 0.59, Confidence Interval 95: 0.2-2.5, p = 0.48). Subtype F, together with NRTI mutations and longer time on treatment was associated to presence of PI-DRM, to a lower darunavir GSS and to mutations at codon I50. CONCLUSIONS: Among patients with PI-DRM, full activity to darunavir was compromised in almost half of the cases and efforts to detect failure at earlier time are warranted, particularly for HIV-1 subtype F that showed association to the emergence of resistance, with potential impact in protease inhibitors sequencing. Furthermore, NRTI mutations may serve as an indicative of sufficient adherence to allow PI-DRM emergence.

Transmitted Drug Resistance Among Recently Diagnosed Adults and Children in São Paulo, Brazil.

Transmitted drug resistance mutations (TDRM) have been a constant threat to treatment efficacy. We evaluated TDRM in plasma RNA of 217 antiretroviral therapy-naive patients from sites in the São Paulo metropolitan area, collected from 2012 to 2014. The partial HIV-1 polymerase region was sequenced using Big Dye terminators at an ABI 3130 Genetic Analyzer. TDRM was defined according to the Stanford database calibrated population resistance (CPR v.6.0), but other drug resistance mutations (DRM) considered at the IAS list (IAS, 2014) and at the Stanford HIV Database Genotyping Resistance Interpretation (GRI-HIVdb) were also described. Out of 78% (170/217) of patients with information on the time of diagnosis, most (83%, 141/170) had been recently diagnosed, with the first positive HIV serology at a median of 58 days (IQR 18-184). Subtype B predominated (70%), followed by subtype F (10%), BF (7.5%), C (7.5%), and BC (5%). TDRMs were observed in 9.2% (20/217, CI 95% 5.9% to 13.6%), mostly (5.2%) to nonnucleoside reverse transcriptase inhibitor (NNRTI) antiretroviral class. Among children and adolescents, only a single patient showed TDRMs. Additional non-CPR mutations were observed: 11.5% (25/217) according to IAS or 4.6% (10/217) according to GRI-HIVdb. Overall, 23.5% (51/217) of the cases had one or more DRM identified. TDRM prevalence differed significantly among some sites. These trends deserve continuous and systematic surveillance, especially with the new policies of treatment as prevention being implemented in the country.

Prevalence and antimicrobial susceptibility profile of Enterococcus spp isolated from frozen chicken carcasses

Prevalence and antimicrobial susceptibility of Enterococcus spp. were evaluated in 360 frozen unse asoned chicken carcasses samples collected from September 2004 to June 2006 from the retail stores in São Paulo State, Brazil. Enterococcus spp. was isolated from all analyzed samples, and 1,332 strains were identified from them. Among the ten identified species, the predominance of E. faecalis, E. gallinarum, E.casseliflavus and E. faecium was occurred. All of the Enterococci strains showed some degree of resistanceto the nine antimicrobials utilized in the study. The percentages of antimicrobial resistance were: 89.2% for tetracycline, 91.4% for quinupristin-dalfopristin, 83.5% for erythromycin, 65% for ciprofloxacin, 55.4% for chloramphenicol, 6.5% for linezolid, 2.3% for vancomycin, 2.3% for teicoplanin and 0.2% for ampicillin. The occurrence of the high level resistance to amyno glicosides (HLR-A) was detected in 57.4% of the isolates. E. faecalis and E. faecium species, which are considered as important agents in nosocomial infections, showed resistance to eight and seven antibiotics, respectively.