Development of H51Y and E157Q mutations for integrase inhibitor resistance in a patient undergoing treatment for pulmonary tuberculosis: A case report.

Background: Failure of first-line regimens with dolutegravir, a high genetic barrier antiretroviral of the integrase inhibitor class, although uncommon, tends to increase in prevalence due to broader use. Objective: To describe the clinical case of an HIV/Tuberculosis coinfected patient who developed Human Immunodeficieny Virus (HIV) treatment failure during dolutegravir therapy. Case report: Male, 29 years old, presented with a right cervical mass, dry cough, and hyporexia, which lasted 2 weeks. Diagnostic tests were positive for tuberculosis and HIV. The viral load was 437,927 cp/mL (Log = 5.64). Antiretroviral therapy was initiated with Tenofovir/Lamivudine and Dolutegravir (TDF/3TC and DTG), the latter at a dose of 50 mg/day, as was a regimen for tuberculosis. After 8 months, therapeutic failure was verified. Genotyping was requested, with detection of the H51Y and E157Q mutations in the integrase. Conclusion: Attention when determining the antiretroviral therapy treatment regimen of HIV/TB coinfected patients is paramount. Poor adherence to antiretroviral therapy and follow-up may have contributed to treatment failure and resistance.

Telehealth effectiveness for pre-exposure prophylaxis delivery in Brazilian public services: the Combine! Study.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) delivery based on user needs can enhance PrEP access and impact. We examined whether telehealth for daily oral PrEP delivery could change the indicators of care related to prophylactic use in five Brazilian public HIV clinics (testing centres, outpatient clinics and infectious disease hospitals). METHODS: Between July 2019 and December 2020, clients on PrEP for at least 6 months could transition to telehealth or stay with in-person follow-up. Clients were clinically monitored until June 2021. A desktop or mobile application was developed, comprising three asynchronous consultations and one annual in-person consultation visit. Predictors influencing telehealth preference and care outcomes were examined. The analysis encompassed intent-to-treat (first choice) and adjustments for sexual practices, schooling, age, duration of PrEP use and PrEP status during the choice period. RESULTS: Of 470 users, 52% chose telehealth, with the adjusted odds ratio (aOR) increasing over time for PrEP use (aOR for 25-months of use: 4.90; 95% CI: 1.32-18.25), having discontinued PrEP at the time of the choice (aOR: 2.91; 95% CI: 1.40-6.06) and having health insurance (aOR: 1.91; 95% CI: 1.24-2.94) and decreasing for those who reported higher-risk behaviour (aOR for unprotected anal sex: 0.51; 95% CI: 0.29-0.88). After an average follow-up period of 1.6 years (95% CI: 1.5-1.7), the risk of discontinuing PrEP (not having the medication for more than 90 days) was 34% lower with telehealth (adjusted hazard ratio: 0.66; 95% CI: 0.45-0.97). When adjusted by mixed linear regression, no differences in adherence (measured by mean medication possession rate) were found between in-person and telehealth (p = 0.486) or at pre- and post-telehealth follow-ups (p = 0.245). Sexually transmitted infections increased between the pre-follow-up and post-follow-up choices and were not associated with in-person or telehealth (p = 0.528). No HIV infections were observed. CONCLUSIONS: Our findings indicate that telehealth for PrEP delivery can enhance service rationalization and reinforce the prevention cascade. This approach reduces prophylaxis interruptions and is mainly preferred by individuals with lower demands for healthcare services.

Cytokines, chemokines, and cells growth factors in patients with mild to moderate SARS-CoV-2 infection: A case-control study.

Several biomarkers have been evaluated as predictors of severity or in directing the treatment of COVID-19, however there are no conclusive results. In this study, we evaluated serum levels of cytokines, chemokines, and cell growth factors in association with the pathobiology of mild to moderate SARS-CoV-2 infection. Serum levels of SARS-CoV-2 infected patients (n = 113) and flu symptoms individuals negative for SARS-CoV-2 (n = 58), tested by the RT-qPCR test-nasal swab were compared to healthy controls (n = 53). Results showed that the proinflammatory cytokines IL-1ß, MCP-3, TNF-α, and G-CSF were increased in symptomatic patients and the cytokines IL-6 and IL-10 were associated with patients positive for SARS-CoV-2 when compared to healthy controls. Symptoms associated with COVID-19 were fever, anosmia, ageusia, and myalgia. For patients without SARS-CoV-2 infection, their major symptom was sore throat. The pathobiology of mild to moderate SARS-CoV-2 infection was associated with increasing proinflammatory cytokines and a pleiotropic IL-6 and anti-inflammatory IL-10 cytokines compared to healthy controls. Thus, knowledge about the pathophysiology and the involvement of biomarkers in the mild to moderate profile of the disease should be evaluated. Monitoring these biomarkers in patients with mild to moderate disease can help establish adequate treatment and prevention strategies for long-term COVID-19.

Detection of SARS-CoV-2 in different human biofluids using the loop-mediated isothermal amplification assay: A prospective diagnostic study in Fortaleza, Brazil.

We adopted the reverse-transcriptase-loop-mediated isothermal amplification (RT-LAMP) to detect severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) in patient samples. Two primer sets for genes N and Orf1ab were designed to detect SARS-CoV-2, and one primer set was designed to detect the human gene Actin. We collected prospective 138 nasopharyngeal swabs, 70 oropharyngeal swabs, 69 salivae, and 68 mouth saline wash samples from patients suspected to have severe acute respiratory syndrome (SARS) caused by SARS-CoV-2 to test the RT-LAMP in comparison with the gold standard technique reverse-transcription quantitative polymerase chain reaction  (RT-qPCR). The accuracy of diagnosis using both primers, N5 and Orf9, was evaluated. Sensitivity and specificity for diagnosis were 96% (95% confidence interval [CI]: 87-99) and 85% (95% CI: 76-91) in 138 samples, respectively. Accurate diagnosis results were obtained only in nasopharyngeal swabs processed via extraction kit. Accurate and rapid diagnosis could aid coronavirus disease 2019 (COVID-19) pandemic management by identifying, isolating, and treating patients rapidly.

Nonoccupational post-exposure prophylaxis for HIV after sexual intercourse among women in Brazil: Risk profiles and predictors of loss to follow-up.

Access to antiretroviral-based HIV prevention has been marked by sex asymmetries, and its effectiveness has been compromised by low clinical follow-up rates. We investigated risk profiles of women who received nonoccupational post-exposure prophylaxis (nPEP), as well as the rates and predictive factors of loss to follow-up after nPEP initiation.Retrospective study evaluating 501 women who received nPEP between 2014 and 2015 at 5 HIV centers (testing centers-VCT, outpatient clinics, and infectious diseases hospital). Risk profiles were drawn based on the characteristics of the women and their sexual partners, and then stratified by sociodemographic indicators and previous use of HIV prevention services. Loss to follow-up (LTFU) was defined as not presenting for follow-up visits or for HIV testing after nPEP initiation. Predictors of LTFU were analyzed by calculating adjusted prevalence ratios (aPRs).Approximately 90% of women had sexual encounters that met the criteria established in the Brazilian guidelines for nPEP. Those who declared to be sex workers (26.5%) or drug users (19.2%) had the highest social vulnerability indicators. In contrast, women who had intercourse with casual partners of unknown HIV risk (42.7%) had higher education and less experience with previous HIV testing (89.3%) or nPEP use (98.6%). Of the women who received nPEP after sexual intercourse with stable partners, 75.8% had HIV-infected partners. LTFU rate was 72.8% and predictors included being Black (aPR = 1.15, 95% confidence interval [CI]: 1.03-1.30), using drugs/alcohol (aPR = 1.15, 95% CI: 1.01-1.32) and having received nPEP at an HIV outpatient clinic (aPR = 1.35, 95% CI: 1.20-1.51) or at an infectious diseases hospital (aPR = 1.37, 95% CI: 1.11-1.69) compared with a VCT. The risk of LTFU declined as age increased (aPR 41-59 years = 0.80, 95% CI: 0.68-0.96).Most women who used nPEP had higher socioeconomic status and were not part of populations most affected by HIV. In contrast, factors that contribute to loss to follow-up were: having increased social vulnerability; increased vulnerability to HIV infection; and seeking nPEP at HIV treatment services as opposed to at a VCT.

Effectiveness of first-wave protease inhibitors in hepatitis C virus genotype 1 infection: a multicenter study in Brazil.

INTRODUCTION: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. METHODS: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant. RESULTS: Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia. CONCLUSIONS: The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.

Effectiveness of first-wave protease inhibitors in hepatitis C virus genotype 1 infection: a multicenter study in Brazil

Abstract INTRODUCTION: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. METHODS: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant. RESULTS: Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia. CONCLUSIONS: The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.

Association of IL10, IL4, IFNG, and CTLA4 Gene Polymorphisms with Efavirenz Hypersensitivity Reaction in Patients Infected with Human Immunodeficiency Virus.

We evaluated interleukin-10 (IL10) －592 C/A, IL4－589 C/T, interferon gamma (IFNG)＋874 A/T, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)＋49 A/G gene polymorphisms associated with efavirenz hypersensitivity reaction. A total of 63 human immunodeficiency virus-positive patients under treatment at a public hospital were included in the study, of whom 21 presented with efavirenz hypersensitivity. Patients who presented with efavirenz hypersensitivity reaction showed a higher frequency of the IL10 －592A allele than the controls (p＝0.028). The allele A was associated with increased risk of efavirenz hypersensitivity (odds ratio＝2.40). In case of IL4, a significant difference in the frequency of the IL4 －589 (C/T) polymorphism was not observed between patients and controls. A significant inverse correlation was observed when comparing the CTLA4＋49A/G and IL4 －589 C/T polymorphisms (r＝－0.650, p＝0.001); that is, the CTLA4 +49GG genotype, involved with the lowest capacity of inhibition, was inversely correlated IL4－589TT genotype, which induces high production of IL-4. With respect to the CTLA4＋49A/G and IFNG＋874T/A gene polymorphisms, significant differences in allele and genotype frequencies were not observed between the groups. Therefore, our data suggest that polymorphisms in regulatory regions of cytokine genes could modulate an individual's susceptibility to efavirenz hypersensitivity reaction.

CD38+CD8+ and CD38+CD4+ T Cells and IFN Gamma (+874) Polymorphism Are Associated with a Poor Virological Outcome.

The main objective of the work was to evaluate the use of CD38 on T lymphocytes, IFNγ (+874 A/T), and IL-10 (-1082 A/G) polymorphisms in HIV-infected patients under antiretroviral (ARV) therapy. Sixty-one patients were selected at the outpatient clinic for HIV infection at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. The patients were classified into two groups, according to viral load after one year of ARV therapy. In the aviremic group (group I), a reduction of 35.5% of CD38+CD4+ T cells was observed (p = 0.02) and 49.3% of CD38+CD8+ T cells (p = 0.001). In the viremic group (group II), a reduction of 37.2% of CD38+CD4+ T cells (p = 0.067), and 21.4% of CD38+CD8+ T cells (p = 0.60) occurred. No association was found between IL-10 (-1082) polymorphism and the type of response to ARV therapy. Regarding the gene polymorphism on IFNγ (+874 T/A), 73.34% of group I and 33.3% of group II presented the AA genotype. The relative risk of the individuals carrying AA genotype or the A allele and not being able to suppress the viral load level after one year of ARV therapy was 3.44 (1.25-9.45; p = 0.014) or 2.35 (1.05-5.26; p = 0.027), respectively. Our data suggested that an augmented frequency of activated CD38+CD8+ T cells as well as the presence of the A allele of IFNγ polymorphism could contribute to a reduced virological suppression in patients under antiretroviral therapy.

Pre-exposure and postexposure prophylaxes and the combination HIV prevention methods (The Combine! Study): protocol for a pragmatic clinical trial at public healthcare clinics in Brazil.

INTRODUCTION: Few results from programmes based on combination prevention methods are available. We propose to analyse the degree of protection provided by postexposure prophylaxis (PEP) for consensual sexual activity at healthcare clinics, its compensatory effects on sexual behaviour; and the effectiveness of combination prevention methods and pre-exposure prophylaxis (PrEP), compared with exclusively using traditional methods. METHODS AND ANALYSIS: A total of 3200 individuals aged 16 years or older presenting for PEP at 5 sexually transmitted disease (STD)/HIV clinics in 3 regions of Brazil will be allocated to one of two groups: the PEP group-individuals who come to the clinic within 72 h after a sexual exposure and start PEP; and the non-PEP group-individuals who come after 72 h but within 30 days of exposure and do not start PEP. Clinical follow-up will be conducted initially for 6 months and comprise educational interventions based on information and counselling for using prevention methods, including PrEP. In the second study phase, individuals who remain HIV negative will be regrouped according to the reported use of prevention methods and observed for 18 months: only traditional methods; combined methods; and PrEP. Effectiveness will be analysed according to the incidence of HIV, syphilis and hepatitis B and C and protected sexual behaviour. A structured questionnaire will be administered to participants at baseline and every 6 months thereafter. Qualitative methods will be employed to provide a comprehensive understanding of PEP-seeking behaviour, preventive choices and exposure to HIV. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the resolution of the School of Medicine Research Ethics Commission of Universidade de São Paulo (protocol no. 251/14). The databases will be available for specific studies, after management committee approval. Findings will be presented to researchers, health managers and civil society members by means of newspapers, electronic media and scientific journals and meetings.

Consensus of the Brazilian Society of Infectious Diseases and Brazilian Society of Clinical Oncology on the management and treatment of Kaposi's sarcoma

Kaposi's sarcoma is a multifocal vascular lesion of low-grade potential that is most often present in mucocutaneous sites and usually also affects lymph nodes and visceral organs. The condition may manifest through purplish lesions, flat or raised with an irregular shape, gastrointestinal bleeding due to lesions located in the digestive system, and dyspnea and hemoptysis associated with pulmonary lesions. In the early 1980s, the appearance of several cases of Kaposi's sarcoma in homosexual men was the first alarm about a newly identified epidemic, acquired immunodeficiency syndrome. In 1994, it was finally demonstrated that the presence of a herpes virus associated with Kaposi's sarcoma called HHV-8 or Kaposi's sarcoma herpes virus and its genetic sequence was rapidly deciphered. The prevalence of this virus is very high (about 50%) in some African populations, but stands between 2% and 8% for the entire world population. Kaposi's sarcoma only develops when the immune system is depressed, as in acquired immunodeficiency syndrome, which appears to be associated with a specific variant of the Kaposi's sarcoma herpes virus. There are no treatment guidelines for Kaposi's sarcoma established in Brazil, and thus the Brazilian Society of Clinical Oncology and the Brazilian Society of Infectious Diseases developed the treatment consensus presented here.

Interleukin-10 gene polymorphism (-1082G/A) and allergy to efavirenz in patients infected with human immunodeficiency virus.

The aim of the present study was to investigate the association between polymorphism in the interleukin-10 gene promoter at position -1082 in human immunodeficiency virus-infected patients who had presented allergic reaction due to efavirenz. The study included 63 patients treated at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. Twenty-one patients who had presented allergic reaction to efavirenz were compared to 42 patients with no allergic reaction following exposure to this drug. Blood samples were collected for DNA extraction and submitted to the restriction fragment length polymorphism - polymerase chain reaction technique. The -1082AA genotype was significantly more frequent in allergic patients as compared to non-allergic patients (p=0.019; χ(2)=5.534; OR=3.625; 95% CI=1.210-10.860). Likewise the allele IL-10 -1082A was identified significantly more often among efavirenz allergic patients than in the non-allergic group (p=0.009; χ(2)=6.787; OR=3.029; 95% CI=1.290-7.111). These findings suggest that the polymorphism in the interleukin-10 gene promoter -1082G/A can be related to the development of allergic reactions to efavirenz.

Consensus of the Brazilian Society of Infectious Diseases and Brazilian Society of Clinical Oncology on the management and treatment of Kaposi's sarcoma.

Kaposi's sarcoma is a multifocal vascular lesion of low-grade potential that is most often present in mucocutaneous sites and usually also affects lymph nodes and visceral organs. The condition may manifest through purplish lesions, flat or raised with an irregular shape, gastrointestinal bleeding due to lesions located in the digestive system, and dyspnea and hemoptysis associated with pulmonary lesions. In the early 1980s, the appearance of several cases of Kaposi's sarcoma in homosexual men was the first alarm about a newly identified epidemic, acquired immunodeficiency syndrome. In 1994, it was finally demonstrated that the presence of a herpes virus associated with Kaposi's sarcoma called HHV-8 or Kaposi's sarcoma herpes virus and its genetic sequence was rapidly deciphered. The prevalence of this virus is very high (about 50%) in some African populations, but stands between 2% and 8% for the entire world population. Kaposi's sarcoma only develops when the immune system is depressed, as in acquired immunodeficiency syndrome, which appears to be associated with a specific variant of the Kaposi's sarcoma herpes virus. There are no treatment guidelines for Kaposi's sarcoma established in Brazil, and thus the Brazilian Society of Clinical Oncology and the Brazilian Society of Infectious Diseases developed the treatment consensus presented here.

Virologic and immunologic effectiveness at 48 weeks of darunavir-ritonavir-based regimens in treatment-experienced persons living with HIV-1 infection in clinical practice: a multicenter Brazilian cohort.

INTRODUCTION: Published data addressing the effectiveness of darunavir-ritonavir (DRV/r)-based therapy for multiexperienced patients in developing countries are scarce. This study evaluated the 48-week virologic and immunologic effectiveness of salvage therapy based on DRV/r for the treatment of multidrug-experienced HIV-1-infected adults in Brazil. MATERIALS AND METHODS: A multicenter retrospective cohort study was carried out with multidrug-experienced adults who were on a failing antiretroviral therapy and started a DRV/r-based salvage therapy between 2008 and 2010. The primary effectiveness end point was the proportion of patients with virologic success (plasma HIV-1 RNA <50 copies/mL at week 48). RESULTS: At 48 weeks, 73% of the patients had HIV-RNA <50 copies/mL and a mean increase of 108 CD4 cells/mm(3). Higher baseline viral load, lower baseline CD4 count, younger age, and 3 or more DRV/r-associated resistance mutations were significantly predictive of virologic failure. Concomitant use of raltegravir was strongly associated with virologic success. CONCLUSION: The use of DRV/r-based regimens for salvage therapy is an effective strategy in the clinical care setting of a developing country.

Factors determining changes in initial antiretroviral therapy.

OBJECTIVE: To investigate factors determining changes in initial antiretroviral therapy (ART) in patients attended to in an AIDS tertiary care hospital in Ceará, Brazil. METHODS: This descriptive and exploratory study used the analysis of request to initiate or change treatment forms in the year of 2008, and the changes in therapy were followed through the first year of treatment. Data were analyzed with SPSS and EpiInfo by using ANOVA and the exact test of the coefficient of contingency, with significance at p < 0.05. RESULTS: From 301 patients initiating ART, 22.1% (n = 68) needed a change in the first year. These patients were mostly males, aged 20 to 39 years; with only one ART changed needed in 86.8% of the cases (n = 59). Reports of two or three changes in regimen were observed. Zidovudine was the drug most often changed, followed by lopinavir/ritonavir and efavirenz. A significant association was found between changes in initial regimens and the report of adverse reactions (p < 0.001). CONCLUSION: The main factor determining changes in the initial ART was an adverse reaction report. Most patients had one change in the initial ART over the first year of treatment. ART monitoring contributed to a better control of the specific drug therapy.

Fatores determinantes para modificações da terapia antirretroviral inicial / Factors determining changes in initial antiretroviral therapy

OBJETIVO: Investigar os fatores determinantes das mudanças da terapia antirretroviral (TARV) inicial dos pacientes assistidos em hospital de referência em AIDS do Ceará. MÉTODOS: O estudo descritivo e exploratório utilizou a análise dos formulários de solicitação de início ou modificação de tratamento do ano de 2008, acompanhando as mudanças de terapia durante o primeiro ano de tratamento. Os dados foram analisados nos programas Statistical Package for the Social Sciences (SPSS) e Epi Info, utilizando ANOVA e teste exato do coeficiente de contingência, com significância de p < 0,05. RESULTADOS: Dos 301 pacientes que iniciaram TARV, 22,1% (n = 68) realizaram troca no primeiro ano. Os pacientes eram, na maioria, do sexo masculino, de idade entre 20 e 39 anos, e fizeram apenas uma mudança da TARV (86,8%; n = 59). Registros de duas ou três mudanças de esquema foram observados. A zidovudina foi o fármaco mais substituído, seguido por lopinavir/ritonavir e efavirenz. Existiu associação significante entre as trocas dos esquemas iniciais com o relato de ocorrência de reações adversas (p < 0,001). CONCLUSÃO: O principal fator determinante para as mudanças de TARV inicial foi o relato de ocorrência de reações adversas. A maioria dos pacientes fez somente uma mudança na TARV inicial durante o primeiro ano de tratamento. O monitoramento da TARV contribuiu para melhor controle da farmacoterapia específica.

OBJECTIVE: To investigate factors determining changes in initial antiretroviral therapy (ART) in patients attended to in an AIDS tertiary care hospital in Ceará, Brazil. METHODS: This descriptive and exploratory study used the analysis of request to initiate or change treatment forms in the year of 2008, and the changes in therapy were followed through the first year of treatment. Data were analyzed with SPSS and EpiInfo by using ANOVA and the exact test of the coefficient of contingency, with significance at p < 0.05. RESULTS: From 301 patients initiating ART, 22.1% (n = 68) needed a change in the first year. These patients were mostly males, aged 20 to 39 years; with only one ART changed needed in 86.8% of the cases (n = 59). Reports of two or three changes in regimen were observed. Zidovudine was the drug most often changed, followed by lopinavir/ritonavir and efavirenz. A significant association was found between changes in initial regimens and the report of adverse reactions (p < 0.001). Conclusion: The main factor determining changes in the initial ART was an adverse reaction report. Most patients had one change in the initial ART over the first year of treatment. ART monitoring contributed to a better control of the specific drug therapy.

Short communication: intermediate prevalence of HIV type 1 primary antiretroviral resistance in Ceará State, Northeast Brazil.

Brazil is a large developing country where almost all FDA-licensed antiretrovirals are made available to more than 200,000 individuals under antiretroviral treatment. General primary HIV-1 resistance in Brazil is assumed to be low, but data are scarce, especially in the Northeast region. To evaluate the prevalence of primary HIV-1 antiretroviral resistance in the state of Ceará, Brazil, a cross-sectional prospective study of antiretroviral-naive HIV-1-infected individuals was performed between May 2008 and May 2009. Genomic sequences of reverse transcriptase and protease regions of the pol gene of HIV-1 using PCR products were obtained. Mutations related to resistance to NRTI, NNRTI, and PI were evaluated according to the WHO mutation list for primary resistance surveillance, which excludes common polymorphisms. Seventy-four individuals were evaluated (50% male) with a median age 30 years; 55.4% were men who have sex with men. Median CD4(+) T lymphocyte counts were 418 and 960 cells/mm(3) and the median viral loads were 4.41 and 4.46 log(10) RNA copies/ml for individuals older and younger that 18 years, respectively. Twenty-seven percent of patients were symptomatic. Five patients (6.8%) were recently infected, as detected by the BED test. The mutations 41L, 67N, 215D, 219Q, 101E, and 103N in the RT and 32I, 46I, 54V, 82T, and 90M, in the PR were identified in 9.5% of samples, more frequently in HIV subtype B (85.1%). A significant level of primary HIV resistance was detected in urban Northeast Brazil, a region geographically distant from the more highly populated and wealthier areas of Southeast Brazil, and this emphasizes the need for monitoring resistance in the studied area.

Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus

Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flipflop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

Impact of the number of failed therapeutic regimes on the development of resistance mutations to HIV-1 in northeast Brazil.

Highly-potent antiretroviral therapy is necessary to avoid viral replication in HIV patients; however, it can favor the appearance of resistance mutations. The mutations 41L, 67N, 70R, 210W, 215Y/F, 219E/Q, 44D and 118I are defined as nucleoside analogous mutations (NAMs), because they affect the efficacy of all nucleoside reverse transcriptase inhibitors (NRTI). The mutation most frequently associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is 103N. 33W/F, 82A/F/L/T, 84V and 90M are called protease inhibitor resistance-associated mutations (PRAM), because they are associated with resistance to several protease inhibitors (PI). This study evaluated the development of resistance mutations and examine the susceptibility of HIV with these mutations to antiretrovirals in HIV-1 patients who have failed one or more therapy regimes. Analyses were made of 101 genotypic tests of patients with therapeutic failure to 2 or 3-drug regimens with NRTI, NNRTI or PI. We used the Stanford database to define the susceptibility profile of the viruses. The samples were divided into three treatment-failure groups: first (F), second (S) and multi-failure (MF) to antiretroviral regimens, and we correlated these groups with resistance profiles and principal mutations. There was a significant increase in resistance mutations V82A/F/L/T, I84V, L90M, M41L, K70R, L210W, T215Y/F and K219Q/E in MF. We also found significantly higher resistance to zidovudine, didanosine, stavudine and abacavir in MF. There was no increase in resistance to tenofovir (p=0.28) and lopinavir (p=0.079) in MF. A high degree of resistance to NNRTIs was observed in all groups. Increased resistance mutations will affect future therapeutic options for HIV patients in Brazil because it results in a significant increase in resistance to antiretroviral drugs.