High Prevalence of Drug Resistance Mutations Among Patients Failing First-Line Antiretroviral Therapy and Predictors of Virological Response 24 Weeks After Switch to Second-Line Therapy in São Paulo State, Brazil.

Universal antiretroviral treatment with sustained viral suppression benefits patients and reduces HIV transmission. Effectiveness of therapy may be limited by antiretroviral drug resistance. Information on the resistance profile at treatment failure and its impact on antiretroviral drugs may subsidize subsequent treatment strategies. Partial pol sequences from 319 patients failing first-line therapy were analyzed for resistance associated mutations (RAMs) and HIV subtype. Demographic data, CD4 T cell count, viral load, and antiretroviral regimens and mutational profile at first-line failure were also investigated for associations to the response to second-line regimens. RAMs at the reverse transcriptase gene were frequent. Most sequences (88%) showed at least one mutation. A higher number of reverse transcriptase RAMs were associated to lower CD4 T cell counts and the use of tenofovir/lamivudine in first line. Among 205 with follow-up data, 76.6% were virally suppressed (below 200 copies/ml) after 24 weeks of second-line therapy. Most cases initiated second line with a regimen genotypic susceptibility score ≥2, but it did not predict viral suppression, that was independently associated with higher CD4 T cell counts and with the presence of nucleos(t)ide analog reverse transcriptase inhibitor (NRTI) RAMs. This study documented extensive resistance at first-line failure in this area in Brazil, highlights the risks of low CD4 T cell counts to second-line therapy, and supports the notion that recycled NRTIs may contribute to viral suppression even when genotypic resistance is present.

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.

Antiretroviral treatment adherence in childhood and adolescence: multidisciplinary team as an associated factor in Brazil.

Our aim was to analyze factors associated with non-adherence to antiretroviral (ARV) treatment among children and adolescents. A cross-sectional study was carried out involving non-institutionalized children and adolescents between 2 and 20 years of age, addressing non-adherence to ARV treatment, which was defined as taking ≤89% of the medications on the day of the interview and the three previous days. The investigation into the association between non-compliance and the variables of interest was performed using unconditional logistic regression. The independent factors associated with non-adherence were forgetfulness (OR = 3.22; 95%CI = 1.75-5.92), difficulties coping with treatment (OR = 2.65; 95%CI = 1.03-6.79), and living with grandparents (OR = 2.28; 95%CI = 1.08-4.83), whereas a protective effect was found with participation in multidisciplinary activities (OR = 0.49; 95%CI = 0.25-0.96), i.e., this factor indicates that the exposure to the variable is beneficial, promoting adherence. We concluded that forgetting to take the medications and reporting having difficulty coping with ARV treatment are potentially modifiable factors through educational and programmatic actions. Residing with one's grandparents may strongly impact adherence to ARV treatment, indicating the need for the systematic support of these family members. Participation in multidisciplinary activities should be stimulated at health-care services.

High frequency of BF mosaic genomes among HIV-1-infected children from Sao Paulo, Brazil.

HIV-1 genetic diversity information from a pediatric population is scarce. This study enrolled 128 children living with HIV/AIDS, 103 antiretroviral-treated and 25 naive, from the Sao Paulo metropolitan area. Gag, pol and env regions were amplified, and drug resistance mutations, V3 loop, tropism and viral clades were evaluated. Drug resistance mutations among naïve children infected by vertical transmission were uncommon (4.2%), whereas most ARV-experienced children showed extensive mutation patterns. Clade B predominated at the pol region, but the analysis of the three regions concatenated showed 28% with BF mosaic structures. The most common V3 motif was GPGR, followed by GWGR in clade B samples and GPGQ in clade F samples. A predicted X4 phenotype was observed in 27%, without correlation to HIV clade. These findings expand the limited information on molecular characteristics of HIV-1 among children living with HIV/AIDS in the area and may provide information useful for monitoring the epidemic.

Meningite Viral / Viral Meningitis

A meningite viral caracteriza-se por um quadro clínico de alteração neurológica, que, em geral, evolui de forma benigna. Os casos podem ocorrer isoladamente, embora o aglomerado de casos (surtos) seja comum. Indivíduos de todas as idades são suscetíveis, porém a faixa etária de maior risco é a de menores de 5 anos. Aproximadamente 85% dos casos são devido ao grupo dos Enterovírus, dentre os quais se destacam os Poliovírus, os Echovírus e os Coxsackievírus dos grupos A e B 1,2. O manejo deve ser adequado para cada etiologia. O presente artigo apresenta as principais etiologias, manejo dos casos, possibilidade diagnóstica e tratamento desta importante entidade nosológica.