Smoking Cessation Is Associated With Short-Term Improvement of Vascular Health in a Cohort of People Living With HIV in Rio de Janeiro, Brazil.

Smoking is highly prevalent in people living with HIV/AIDS (PLHA), leading to detrimental effects in different tissues. We examined the effects of nicotine replacement therapy (NRT) on smoking cessation and vascular health. From December 2019 to October 2021, we prospectively enrolled PLHA who were actively smoking. The primary outcome was endothelial function measured by brachial artery flow-mediated dilatation (FMD). We evaluated the percent change in FMD compared to the baseline measure (Δ%FMD) to detect improvements among participants who quit smoking. To confirm the results, we used linear regression models to account for classical cardiovascular (CV) confounders. We included 117 participants with median age of 45.5 years (IQR= 36.4-54.8); 22 (20.4%) had hypertension, 9 (8.3%) had diabetes, almost half were smoking 20+ cigarettes/day (41.7%). After 12 weeks 30.76% participants quit smoking. Comparison of Δ%FMD change from baseline to week 12 showed that among participants adherent to therapy, there has been an increase in Δ%FMD when compared to those who relapsed (1.17% [0.29-2.98] vs -0.19% [-1.95-0.91], p<0.001). After adjustment for CV factors, multiple linear regression showed that Δ%FMD in participants who quit smoking presented a 2.54 mean increase in comparison to those who continued smoking (p=0.007). In conclusion, this study provides evidence that a strategy of NRT and counseling is modestly effective for smoking cessation in PLHA and improves vascular health in a short period of time. This reinforces the importance of the widespread anti-tobacco programs in HIV clinics and the expected impact lowering the incidence of future cardiovascular events.

Inflammasome genes polymorphisms are associated with progression to mechanical ventilation and death in a cohort of hospitalized COVID-19 patients in a reference hospital in Rio de Janeiro, Brazil.

COVID-19 has a broad spectrum of clinical manifestations. We assessed the impact of single nucleotide polymorphisms (SNPs) of inflammasome genesas risk factors for progression toCOVID-19 critical outcomes, such as mechanical ventilation support (MVS) or death.The study included 451 hospitalized individuals followed up at the INI/FIOCRUZ, Rio de Janeiro, Brazil, from 06/2020 to 03/2021. SNPs genotyping was determined by Real-Time PCR. We analyzed risk factors for progression to MVS (n = 174[38.6 %]) or death (n = 175[38.8 %])as a result of COVID-19 by Cox proportional hazardmodels.Slower progression toMVSwas associated with allele G (aHR = 0.66;P = 0.005) or the genotype G/G (aHR = 0.391;P = 0.006) in the NLRP3 rs10754558 or the allele G (aHR = 0.309;P = 0.004) in the IL1ßrs1143634, while C allele in the NLRP3 rs4612666 (aHR = 2.342;P = 0.006) or in the rs10754558 (aHR = 2.957;P = 0.005) were associated with faster progression to death. Slower progression to death was associated to allele G (aHR = 0.563;P = 0.006) or the genotype A/G (aHR = 0.537;P = 0.005) in the CARD8 rs6509365; the genotype A/C in the IFI16 rs1101996 (aHR = 0.569;P = 0.011); the genotype T/T (aHR = 0.394;P = 0.004) or allele T (aHR = 0.68;P = 0.006) in the NLRP3 rs4612666, and the genotype G/G (aHR = 0.326;P = 0.005) or allele G (aHR = 0,68;P = 0.014) in the NLRP3 rs10754558. Our results suggest that inflammasome genetic variations might influence the critical clinical course of COVID-19.

The first case of acute HIV and monkeypox coinfection in Latin America

ABSTRACT Monkeypox (MPX) transmission outside non-endemic countries has been reported since May 2022, rapidly evolving into a multi-country outbreak. A potential role of sexual contact in transmission dynamics, as well as a predominance of anogenitallesions, are remarkable features of current cases. Screening for sexually transmitted infections (STIs) plays an important role in the evaluation of patients with suspected MPX infection. Herein we report the first case of a patient diagnosed with both MPX and acute HIV infection in Latin America. He had no major complications during his clinical course, and antiretroviral therapy was promptly initiated. Diagnosis of acute HIV requires a high level of suspicion and appropriate laboratory investigation. Health practitioners need to consider this diagnosis while evaluating patients with suspected MPX with a recent unprotected sexual contact.

Inflammasome Genetic Variants Are Associated with Protection to Clinical Severity of COVID-19 among Patients from Rio de Janeiro, Brazil.

COVID-19 has a broad spectrum of clinical manifestations, from asymptomatic or mild/moderate symptoms to severe symptoms and death. The mechanisms underlying its clinical evolution are still unclear. Upon SARS-CoV-2 infection, host factors, such as the inflammasome system, are activated by the presence of the virus inside host cells. The search for COVID-19 risk factors is of relevance for clinical management. In this study, we investigated the impact of inflammasome single-nucleotide polymorphisms (SNPs) in SARS-CoV-2-infected individuals with distinct severity profiles at clinical presentation. Patients were divided into two groups according to disease severity at clinical presentation based on the WHO Clinical Progression Scale. Group 1 included patients with mild/moderate disease (WHO < 6; n = 76), and group 2 included patients with severe/critical COVID-19 (WHO ≥ 6; n = 357). Inpatients with moderate to severe/critical profiles were recruited and followed-up at Hospital Center for COVID-19 Pandemic - National Institute of Infectology (INI)/FIOCRUZ, RJ, Brazil, from June 2020 to March 2021. Patients with mild disease were recruited at Oswaldo Cruz Institute (IOC)/FIOCRUZ, RJ, Brazil, in August 2020. Genotyping of 11 inflammasome SNPs was determined by real-time PCR. Protection and risk estimation were performed using unconditional logistic regression models. Significant differences in NLRP3 rs1539019 and CARD8 rs2043211 were observed between the two groups. Protection against disease severity was associated with the A/A genotype (ORadj = 0.36; P = 0.032), allele A (ORadj = 0.93; P = 0.010), or carrier-A (ORadj = 0.45; P = 0.027) in the NLRP3 rs1539019 polymorphism; A/T genotype (ORadj = 0.5; P = 0.045), allele T (ORadj = 0.93; P = 0.018), or carrier-T (ORadj = 0.48; P = 0.029) in the CARD8 rs2043211 polymorphism; and the A-C-G-C-C (ORadj = 0.11; P = 0.018), A-C-G-C-G (ORadj = 0.23; P = 0.003), C-C-G-C-C (ORadj = 0.37; P = 0.021), and C-T-G-A-C (ORadj = 0.04; P = 0.0473) in NLRP3 genetic haplotype variants. No significant associations were observed for the other polymorphisms. To the best of our knowledge, this is the first study demonstrating an association between CARD8 and NLRP3 inflammasome genetic variants and protection against COVID-19 severity, contributing to the discussion of the impact of inflammasomes on COVID-19 outcomes.

Impact of feminizing hormone therapy on tenofovir and emtricitabine plasma pharmacokinetics: a nested drug-drug interaction study in a cohort of Brazilian transgender women using HIV pre-exposure prophylaxis.

OBJECTIVES: Potential interactions between feminizing hormone therapy (FHT) and pre-exposure prophylaxis (PrEP) may be a barrier to PrEP use among transgender women (TGW). We aimed to assess the impact of FHT on PrEP plasma pharmacokinetics (PK) among TGW. METHODS: This was a PK substudy of the effects of FHT on tenofovir disoproxil fumarate/emtricitabine nested to a trans-specific PrEP demonstration study (NCT03220152). Participants were assigned to receive PrEP only (noFHT) or standardized FHT (sFHT; oestradiol valerate 2-6 mg plus spironolactone 100-300 mg) plus PrEP for 12 weeks, after which they could start any FHT (aFHT). Short- and long-term PK assessment occurred at Weeks 12 and 30-48, respectively (plasma samples prior and 0.5, 1, 2, 4, 6, 8 and 24 h after dose). Non-compartmental PK parameters of tenofovir and emtricitabine were compared as geometric mean ratios (GMRs) between noFHT and PrEP and FHT (sFHT at short-term PK; aFHT at long-term PK) participants. RESULTS: No differences in tenofovir and emtricitabine plasma PK parameters were observed between the short-term PK of noFHT (n = 12) and sFHT participants (n = 18), except for emtricitabine Cmax [GMR: 1.15 (95% CI: 1.01-1.32)], or between noFHT short-term PK and aFHT long-term PK (n = 13). Most participants were on oestradiol valerate 2 mg at the short-term PK (56%) and 4 mg at the long-term PK (54%). Median (IQR) oestradiol levels were 56.8 (43.2-65.4) pg/mL at short-term PK (sFHT) and 44.8 (24.70-57.30) pg/mL at long-term PK (aFHT). No participants in this analysis seroconverted during the study. CONCLUSIONS: Our results indicate no interaction of FHT on tenofovir levels, further supporting PrEP use among TGW using FHT.

Kidney function and daily emtricitabine/tenofovir disoproxil fumarate pre-exposure prophylaxis against HIV: results from the real-life multicentric demonstrative project PrEP Brazil.

BACKGROUND: Pre-Exposure Prophylaxis (PrEP) has demonstrated efficacy in the reduction of sexually transmitted HIV infections. The prolonged use of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) co-formulation (TDF/FTC), however, may result in augmented risk of renal toxicity. We aimed to evaluate changes in the estimated Glomerular Filtration Rate (eGFR) in a real-world population setting of participants enrolled in PrEP Brazil, a 48-week prospective, open-label, demonstration study to assess the feasibility of daily oral TDF/FTC used by men who have sex with men and transgender women at high-risk of HIV infection, all over 18 years old. METHODS: Kidney function was assessed by serial measurement of serum creatinine and eGFR with the Modification of Diet in Renal Disease Study (MDRD) formula on weeks 4, 12, 24, 36 and 48. Adherence to PrEP was assessed by dosing TDF concentration in dried blood spots at weeks 4 and 48, measured by liquid chromatography-mass spectrometry or mass spectrometry. RESULTS: Of 392 participants completing the 48-week follow-up protocol with TDF blood detectable levels and eGFR measures, 43.1% were young adults, of Caucasian ethnic background (57.9%), with BMI below 30 kg/m2, without arterial hypertension. At screening, median eGFR was 93.0 mL/min/1.73 m2. At week 4 follow-up, 90 (23% of the study population) participants presented reductions in eGFR greater than 10 mL/min/1.73 m2 as compared to baseline eGFR, some as large as 59 mL/min/1.73 m2, but with no clinical outcomes (adverse events and renal adverse events) severe enough to demand TDF/FTC discontinuation. A negative relationship was observed between TDF blood levels and eGFR at weeks 4 (r = - 0.005; p < 0.01) and 48 (r = - 0.006; p < 0.01). CONCLUSIONS: These results suggest that the renal function profile in individuals on TDF/FTC may be assessed on week 4 and then only annually, allowing a more flexible medical follow-up in primary care centers.

Transcendendo: A Cohort Study of HIV-Infected and Uninfected Transgender Women in Rio de Janeiro, Brazil.

Purpose: Worldwide, the burden of adverse health conditions is substantial among travestis and transgender women (trans women). Transcendendo, the first trans-specific cohort in a low- or middle-income country, is an open cohort established in August 2015 to longitudinally evaluate the health aspects of trans women aged ≥18 years in Rio de Janeiro, Brazil. Methods: Study visits occur on an annual basis. Data on sociodemographics, behavioral, gender transition, affirmation procedures, hormone use, discrimination, violence, clinical and mental health, HIV prevention, and care (for those HIV-infected) are collected. Physical examination, anthropometric measurements, and laboratory tests are performed. Results: As of July 2017, 322 trans women were enrolled in the cohort with a median age of 31.5 years (interquartile range 25.7-39.5), of whom 174 (54%) were HIV-infected. The Transcendendo baseline information reinforces the scenario of marginalization and deprivation surrounding trans women. Most participants had low income (62.0% were living with below US$ 10.00/day), showed a very high engagement in sex work (78.6%), and reported increased occurrence of sexual (46.3%) and physical (54.0%) violence. Pre-exposure peophylaxis (PReP) was used by 18.8% of the HIV-uninfected trans women, only through research participation. Positive screening for depression (57.8%) and problematic use of tobacco (56.6%), cannabis (28.9%), cocaine (23.8%), and alcohol (21.5%) were high. Almost all participants (94.8%) reported hormone use at some point, mostly without medical supervision (78.7%). Conclusion: Our results describe a context of exclusion experienced by trans women, exposing vulnerabilities of this population in a middle-income country, with poor access to trans-specific care, HIV prevention and care, and mental health care. Addressing transgender experiences and needs can help the development of strategies to diminish stigma, improve health care environment, guide future research on trans morbidities, substance use, and trans-specific interventions to support health-related recommendations. Ultimately, it contributes to close the gaps concerning transgender health and reinforces that trans care cannot be disentangled from the social environment that surrounds trans women.

Incidence rate of modifying or discontinuing first combined antiretroviral therapy regimen due to toxicity during the first year of treatment stratified by age

Toxicity is the most frequently reported reason for modifying or discontinuing the first combined antiretroviral therapy regimens, and it can cause significant morbidity, poor quality of life and also can be an important barrier to adherence, ultimately resulting in treatment failure and viral resistance. Elderly patients with HIV/AIDS (≥50 years) may have a different profile in terms of treatment modification due to higher incidence of comorbidities and polypharmacy. The aim of this study was to describe the incidence of modifying or discontinuing first combined antiretroviral therapy regimen due to toxicity (TOX-MOD) during the first year of treatment at the IPEC – FIOCRUZ HIV/AIDS cohort, Rio de Janeiro, Brazil, stratified by age. Demographic, clinical and treatment characteristics from antiretroviral-naïve patients who first received combined antiretroviral therapy between Jan/1996 and Dec/2010 were collected. Incidence rate and confidence interval of each event were estimated using quasipoisson model. To estimate hazard ratio (HR) of TOX-MOD during the first year of combined antiretroviral therapy Cox's proportional hazards regression was applied. Overall, 1558 patients were included; 957 (61.4%), 420 (27.0%) and 181 (11.6%) were aged <40, 40–49, and ≥50 years, respectively. 239 (15.3%) events that led to any modifying or discontinuing within the first year of treatment were observed; 228 (95.4%) of these were TOX-MOD, corresponding to an incidence rate of 16.6/100 PY (95% CI: 14.6–18.9). The most frequent TOX-MOD during first combined antiretroviral therapy regimen were hematologic (59; 26.3%), central nervous system (47; 20.9%), rash (42; 19.1%) and gastrointestinal (GI) (38; 16.7%). In multivariate analysis, incidence ratio of TOX-MOD during the first year of combined antiretroviral therapy progressively increases with age, albeit not reaching statistical significance. This profile was maintained after adjusting the model for sex, combined antiretroviral therapy regimen and year of combined antiretroviral therapy initiation. These results are important because not only patients are living longer and aging with HIV, but also new diagnoses are being made among the elderly. Prospective studies are needed to evaluate the safety profile of first line combined antiretroviral therapy on elderly individuals, especially in resource-limited countries, where initial regimens are mostly NNRTI-based.

Incidence rate of modifying or discontinuing first combined antiretroviral therapy regimen due to toxicity during the first year of treatment stratified by age.

Toxicity is the most frequently reported reason for modifying or discontinuing the first combined antiretroviral therapy regimens, and it can cause significant morbidity, poor quality of life and also can be an important barrier to adherence, ultimately resulting in treatment failure and viral resistance. Elderly patients with HIV/AIDS (≥ 50 years) may have a different profile in terms of treatment modification due to higher incidence of comorbidities and polypharmacy. The aim of this study was to describe the incidence of modifying or discontinuing first combined antiretroviral therapy regimen due to toxicity (TOX-MOD) during the first year of treatment at the IPEC - FIOCRUZ HIV/AIDS cohort, Rio de Janeiro, Brazil, stratified by age. Demographic, clinical and treatment characteristics from antiretroviral-naïve patients who first received combined antiretroviral therapy between Jan/1996 and Dec/2010 were collected. Incidence rate and confidence interval of each event were estimated using quasipoisson model. To estimate hazard ratio (HR) of TOX-MOD during the first year of combined antiretroviral therapy Cox's proportional hazards regression was applied. Overall, 1558 patients were included; 957 (61.4%), 420 (27.0%) and 181 (11.6%) were aged <40, 40-49, and ≥ 50 years, respectively. 239 (15.3%) events that led to any modifying or discontinuing within the first year of treatment were observed; 228 (95.4%) of these were TOX-MOD, corresponding to an incidence rate of 16.6/100 PY (95% CI: 14.6-18.9). The most frequent TOX-MOD during first combined antiretroviral therapy regimen were hematologic (59; 26.3%), central nervous system (47; 20.9%), rash (42; 19.1%) and gastrointestinal (GI) (38; 16.7%). In multivariate analysis, incidence ratio of TOX-MOD during the first year of combined antiretroviral therapy progressively increases with age, albeit not reaching statistical significance. This profile was maintained after adjusting the model for sex, combined antiretroviral therapy regimen and year of combined antiretroviral therapy initiation. These results are important because not only patients are living longer and aging with HIV, but also new diagnoses are being made among the elderly. Prospective studies are needed to evaluate the safety profile of first line combined antiretroviral therapy on elderly individuals, especially in resource-limited countries, where initial regimens are mostly NNRTI-based.

Efetividade dos esquemas antirretrovirais de primeira e segunda linha utilizados no tratamento de Pacientes com HIV/AIDS numa coorte urbana no Rio de Janeiro / Effectiveness of first- and second-line antirretroviral therapy in a HIV/AIDS urban cohort in Rio de Janeiro, Brazil

Introdução: O Brasil foi o primeiro país em desenvolvimento a implantar um programa de acesso universal ao tratamento antirretroviral (TAR) em larga escala, acarretando aumento da sobrevida da população vivendo com HIV/Aids, diminuição da incidência de infecções oportunistas e diminuição das hospitalizações. [...] Objetivo: Estimar as taxas de efetividade dos esquemas antirretrovirais e fatores associados à resposta ao tratamento e sua durabilidade para TAR de primeira e segunda linhas na coorte de pacientes com HIV/Aids do IPEC-Fiocruz. Primeiro Artigo: Foi estimada a efetividade de TAR de primeira linha no IPEC-Fiocruz e os fatores sóciodemográficos, comportamentais, clínicos e estruturais associados à supressão viral foram avaliados. [...] Entre janeiro de 2000 e junho de 2010, 1.311 pacientes iniciaram TAR de primeira linha, dos quais 987 (75 por cento) utilizaram esquemas baseados em ITRNN. A efetividade foi de 77 por cento, 76 por cento e 68 por cento aos seis, 12 e 24 meses, respectivamente. Fatores associados com supressão viral, definida como ter uma medida de carga viral menor ou igual 400 cópias/mL sem modificação/interrupção de classe, na análise multivariada em 12 meses foram maior escolaridade, início da TAR no calendário mais recente (2005- 2010) e participação em estudo clínico; aos 24 meses nossos resultados sugerem que ser mais velho e usar esquemas baseados em ITRNN são fatores independentemente associados a melhor resposta. Segundo Artigo: Foram descritos os desfechos relacionados a TAR de segunda linha no IPEC Fiocruz, assim como o tempo até a falha e os fatores associados...

Introduction: Brazil was the first developing country to introduce a free access to antiretroviral therapy (cART) for all in need, leading to an increase in HIV/AIDS population survival and a decrease on the incidence of opportunistics infections and hospitalizations. [...] Objective: Evaluate first- and second-line cART effectiveness and factors correlated with response to treatment and its durability in HIV/AIDS IPEC-FIOCRUZ cohort.First Article: First-line cART effectiveness in IPEC-Fiocruz cohort was estimated and sociodemographic,behavioral, clinical and structural factors associated with virologic suppression were evaluated. Virologic suppression was accessed at 6, 12, and 24 months from cARTinitiation. Quasi-Poisson regression was used to quantify the association of factors with virologic suppression at 12 and 24 months. From January 2000 through June 2010, 1,311patients started first-line cART; 987 (75 percent) patients used NNRTI-based regimens. [...] In multivariate analysis, factors associated with virologic suppression, defined ashaving a viral load measurement less than or equal to 400 copies/mL without drug class modification and/or discontinuation, at 12 months were higher formal education, starting cART more recently(2005-2010) and clinical trial participation; for the 24-month endpoint, older age and anNNRTI-based regimen were also independently associated with virologic suppression. Second Article: Second-line cART outcomes in IPEC-Fiocruz cohort were described, including time to failure as well as factors associated with treatment failure...

Aging with HIV: a practical review

The worldwide elderly population is expected to grow by an additional 694 million people by 2025. By that time, there will be approximately two billion elderly people in the world, most of whom (80%) will be living in developing countries. Based on recent estimates, this population will number over 40 million in 2030 in Brazil and a consequent increase in governmental spending for this population can be expected. Since highly active antiretroviral therapy became available in the mid-1990s, the life expectancy of people living with HIV has increased significantly. Approximately 12 million life years were added to the world between 1996 and 2008 as a consequence of wider access to highly active antiretroviral therapy. In Brazil, the incidence of AIDS among the population aged >50 years doubled between 1996 and 2006. The development of antiretroviral therapy has allowed individuals diagnosed at a younger age to live longer, which partially explains the aging tendency associated with the HIV/AIDS epidemic. It is estimated that by 2015, subjects aged >50 years will represent 50% of the people living with HIV undergoing clinical treatment. This scenario presents some challenges, including the fact that the diagnosis of HIV tends to be delayed in older patients compared to younger patients because the symptoms of HIV can be confused with those of other common diseases among the elderly and also because healthcare professionals do not consider this population to be at high risk for HIV infection. In regard to the individuals diagnosed with HIV, a further challenge is presented by the morbidity normally associated with aging. Finally, the elderly also exhibit higher susceptibility to the toxic effects and pharmacological interactions of medications. The present article reviews the literature regarding the profile of HIV infection among individuals aged >50 years focusing on practical features related to the clinical approach and long-term follow-up of this population.

Aging with HIV: an overview of an urban cohort in Rio de Janeiro (Brazil) across decades of life

The introduction of highly active antiretroviral therapy during the 1990s was crucial to the decline in the rates of morbidity and death related to the acquired immunodeficiency syndrome (AIDS) and turned human immunodeficiency virus (HIV) infection into a chronic condition. Consequently, the HIV/AIDS population is becoming older. The aim of this study was to describe the immunological, clinical and comorbidity profile of an urban cohort of patients with HIV/AIDS followed up at Instituto de Pesquisa Clinica Evandro Chagas, Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Retrospective data from 2307 patients during January 1st, 2008 and December 31st, 2008 were collected. For continuous variables, Cuzick's non-parametric test was used. For categorical variables, the Cochran-Armitage non-parametric test for tendency was used. For all tests, the threshold for statistical significance was set at 5%. In 2008, 1023 (44.3%), 823 (35.7%), 352 (15.3%) and 109 (4.7%) were aged 18-39, 40-49, 50-59 and >60 years-old, respectively. Older and elderly patients (>40 years) were more likely to have viral suppression than younger patients (18-39 years) (p 0.001). No significant difference in the latest CD4+ T lymphocyte count in the different age strata was observed, although elderly patients (> 50 years) had lower CD4+ T lymphocyte nadir (p 0.02). The number of comorbidities increased with age and the same pattern was observed for the majority of the comorbidities, including diabetes mellitus, dyslipidemia, hypertension, cardiovascular diseases, erectile dysfunction, HCV, renal dysfunction and also for non-AIDSrelated cancers (p 0.001). With the survival increase associated to successful antiretroviral therapy and with the increasing new infections among elderly group, the burden associated to the diagnosis and treatment of the non-AIDS related HIV comorbidities will grow. Longitudinal studies on the impact of aging on the HIV/AIDS population are still necessary, especially in resource-limited countries.

Aging with HIV: an overview of an urban cohort in Rio de Janeiro (Brazil) across decades of life.

The introduction of highly active antiretroviral therapy during the 1990s was crucial to the decline in the rates of morbidity and death related to the acquired immunodeficiency syndrome (AIDS) and turned human immunodeficiency virus (HIV) infection into a chronic condition. Consequently, the HIV/AIDS population is becoming older. The aim of this study was to describe the immunological, clinical and comorbidity profile of an urban cohort of patients with HIV/AIDS followed up at Instituto de Pesquisa Clinica Evandro Chagas, Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Retrospective data from 2307 patients during January 1st, 2008 and December 31st, 2008 were collected. For continuous variables, Cuzick's non-parametric test was used. For categorical variables, the Cochran-Armitage non-parametric test for tendency was used. For all tests, the threshold for statistical significance was set at 5%. In 2008, 1023 (44.3%), 823 (35.7%), 352 (15.3%) and 109 (4.7%) were aged 18-39, 40-49, 50-59 and ≥60 years-old, respectively. Older and elderly patients (≥40 years) were more likely to have viral suppression than younger patients (18-39 years) (p<0.001). No significant difference in the latest CD4(+) T lymphocyte count in the different age strata was observed, although elderly patients (≥ 50 years) had lower CD4(+) T lymphocyte nadir (p<0.02). The number of comorbidities increased with age and the same pattern was observed for the majority of the comorbidities, including diabetes mellitus, dyslipidemia, hypertension, cardiovascular diseases, erectile dysfunction, HCV, renal dysfunction and also for non-AIDS-related cancers (p<0.001). With the survival increase associated to successful antiretroviral therapy and with the increasing new infections among elderly group, the burden associated to the diagnosis and treatment of the non-AIDS related HIV comorbidities will grow. Longitudinal studies on the impact of aging on the HIV/AIDS population are still necessary, especially in resource-limited countries.

Breast cancer in a cohort of human immunodeficiency virus (HIV)-infected women from Rio de Janeiro, Brazil: a cases series report and an incidence rate estimate.

Highly active antiretroviral therapy (HAART) has changed the morbidity pattern affecting HIV-infected individuals to include non-AIDS-defining cancers. We describe the breast cancer cases occurring in a cohort of 860 HIV-infected women followed in Rio de Janeiro, Brazil, and estimate the incidence rate of breast cancer for this population. Nine cases were identified; median age at diagnosis was 46 years. Median survival after breast cancer diagnosis was 12 months. Breast cancer diagnosis was made within 2 to 15 years of HIV-infection diagnosis. At breast cancer diagnosis, CD4 counts ranged from 135 to 782 cells/mm3; six women were receiving HAART. Histological analysis indicated infiltrating ductal carcinoma in all cases. The incidence rate of breast cancer was 133 cases per 100,000 persons-year. Patients from our case series were late diagnosed with breast cancer and thus suffered from worse prognosis. Strategies targeting earlier diagnosis and prompt initiation of treatment are needed.

CMV and HSV-2 myeloradiculitis in an HIV infected patient / Mieloradiculite por CMV e HSV2 em paciente infectado pelo HIV

While CMV myeloradiculitis is a known complication in AIDS patients with severe immunosuppression, HSV-2 necrotizing myeloradiculitis is rare and often associated with disabling a fatal outcome. We hereby describe a 46 year-old HIV infected patient with profound and sustained immunosuppression who presented with an acute ascending paraparesis and urinary retention. Lumbar spine MRI showed contrast enhancement at the conus medullaris and cauda equine, and both CMV and HSV-2 CSF PCR were positive. Despite treatment, the patient died 20 days later. We review the main diagnostic and therapeutic aspects of herpes virus associated myeloradiculitis and discuss the approach in similar cases.

Enquanto a mieloradiculite pelo CMV é complicação conhecida em pacientes com SIDA e imunossupressão grave, a mieloradiculite necrosante por HSV-2 é rara e muitas vezes associada a sequelas ou desfecho fatal. Descrevemos um paciente de 46 anos de idade, infectado pelo HIV com imunossupressão profunda e sustentada que apresentou paraparesia aguda ascendente e retenção urinária. A RM de coluna lombar mostrou o realce de contraste no cone medular e cauda equina e ambos PCR para CMV e HSV-2 no LCR foram positivos. Apesar do tratamento, o paciente morreu 20 dias depois. Revisamos os principais aspectos diagnósticos e terapêuticos da mieloradiculite associada aos herpesvírus e discutimos a abordagem em casos semelhantes.

Avaliação das razões para modificação e interrupção da terapia anti-retroviaral altamente potente (HAART) em pacientes com infecção pelo HIV tratados em um centro de referência / Evaluation of the reasons for modification and interruption of highly powerful the anti-retroviaral therapy (HAART) in patients with infection for the HIV treated in a reference center

O Brasil foi o primeiro país em desenvolvimento a implementar um programa de acesso universal aos anti-retrovirais. A efetividade desta política de saúde pública foi evidenciada pelo aumento da sobrevida dos pacientes. Dados sobre a duração do primeiro esquema terapêutico, bem como das razões de sua modificação ou interrupção são fundamentais para o planejamento da aquisição e distribuição dos medicamentos no país. Entretanto, esses dados ainda permanecem bastante escassos no nosso meio. Estudar as razões de modificação da primeira terapia anti-retroviral altamente potente (HAART) na coorte de pacientes com HIV/AIDS do Instituto de Pesquisa Clínica Evandro Chagas – IPEC, que iniciaram HAART entre janeiro de 1996 a dezembro de 2005 e foram acompanhados até janeiro de 2007. Estudo de coorte, retrospectivo, avaliando dados demográficos, clínico-laboratoriais e categoria de exposição relacionados às razões de modificação, seu tempo de ocorrência e suas associações de risco através de análise de sobrevida. A probabilidade de modificar o primeiro esquema HAART por quaisquer motivos foi de 44 por cento e o tempo mediano para sua ocorrência de 25 meses. As razões mais freqüentes foram: toxicidades de curto prazo, falha terapêutica, decisão do paciente, toxicidades de longo prazo, e baixa adesão. Decisão do paciente teve maior probabilidade de ocorrência no primeiro ano de HAART (48 por cento). As toxicidades de longo prazo aconteceram no tempo mediano de 32 meses. Fatores de risco variaram conforme a razão, destacando-se maior risco de toxicidades (curto prazo) entre mulheres, (longo prazo) para uso de d4T e esquemas com IP vs ITRNN, ser não-branco e mais velho. De um modo geral, foi identificado menor risco para pacientes utilizando AZT + 3TC + EFV. Apesar da evolução da terapia anti-retroviral, modificações ao longo do tempo, por diferentes razões, continuam ocorrendo para um numero signifcativo de pacientes.

Os dois primeiros anos de HAART mostraram-se críticos nesse estudo, tendo a maioria das modificações ocorrido nesse período. Dessa forma, nessa fase do tratamento todos os esforços precisam ser concentrados para minimizar as razões de troca ou interrupção de HAART.