HIV knowledge and its correlation with the Undetectable = Untransmittable slogan in Brazil.

Knowledge about HIV transmission and prevention is a necessary step for adopting preventive behaviors. We assessed HIV knowledge and its correlation with the perceived accuracy of the "Undetectable = Untransmittable" (U=U) slogan in an online sample with 401 adult Brazilians. Overall, 28% of participants showed high HIV knowledge level. The perceived accuracy of the U=U slogan significantly correlated with HIV knowledge. Younger participants, those reporting lower income or lower education, or who had never tested for HIV showed poorer HIV knowledge. Filling gaps of knowledge among specific populations is urgent in order to increase preventive behaviors and decrease HIV stigma.

Diretrizes para organização, funcionamento e avaliação de farmácias de ensaios clínicos no Brasil: revisão de escopo / Guidelines for organization, operation and evaluation of clinical trials pharmacies in Brazil: a scope review

Resumo O desenvolvimento de novos medicamentos depende de etapas científicas que culminam nos ensaios clínicos em seres humanos. A farmácia de ensaios clínicos (FEC) é o local destinado ao recebimento, preparação, armazenamento e dispensação do produto investigacional (PI). Para tanto, deve possuir infraestrutura e procedimentos que garantam a segurança do participante e a qualidade da pesquisa. Este trabalho teve por objetivo sistematizar diretrizes para FEC no Brasil. Foi realizada uma revisão de escopo e as diretrizes foram organizadas utilizando o método de Ishikawa ("método 6Ms"). No total foram selecionadas 51 publicações, sendo 39 diretrizes e normas e 12 artigos científicos para cada "M"; 25 descreveram o ciclo de assistência farmacêutica (procedimentos para assegurar a segurança dos participantes, desde a requisição do produto até a destinação final), 14 indicadores de qualidade, 12 de recursos humanos, 11 de infraestrutura e recursos materiais e 5 descreveram PIs. para organização, funcionamento e avaliação de FEC no Brasil e corroboram a necessidade da presença do profissional farmacêutico no ciclo da assistência farmacêutica no contexto dos ensaios clínicos, contribuindo ainda na preparação para monitorias, auditorias e inspeções de agências regulatórias.

Abstract The development of new drugs depends on several scientific steps, which culminate in clinical trials. The clinical trials pharmacy (CTP) is the place for receiving, preparing, storing and dispensing the investigational product or study drug. Therefore, it must have infrastructure and procedures that guarantee participant safety and quality of research data. This study aimed to systematize guidelines for CTP in Brazil. We conducted a scope review and organized the results using the Ishikawa Method (6Ms). In total, 51 publications were selected for each "M", 39 laws, regulations or guidelines and 12 scientific articles: 25 publications for pharmaceutical services (pharmacy procedures to ensure participant safety from investigational product ordering to final disposition), 14 for Quality Indicators, 12 for Human Resources, 11 for Infrastructure, 11 for Material Resources and 5 for Investigational Product. Our results synthesize information for the organization, operation and evaluation of CTP in Brazil, emphasizes the inclusion of the pharmacist within the clinical trials context, and contributes to preparation for monitoring, auditing, and inspections conducted by regulatory agencies.

Guidelines for organization, operation and evaluation of clinical trials pharmacies in Brazil: a scope review. / Diretrizes para organização, funcionamento e avaliação de farmácias de ensaios clínicos no Brasil: revisão de escopo.

The development of new drugs depends on several scientific steps, which culminate in clinical trials. The clinical trials pharmacy (CTP) is the place for receiving, preparing, storing and dispensing the investigational product or study drug. Therefore, it must have infrastructure and procedures that guarantee participant safety and quality of research data. This study aimed to systematize guidelines for CTP in Brazil. We conducted a scope review and organized the results using the Ishikawa Method (6Ms). In total, 51 publications were selected for each "M", 39 laws, regulations or guidelines and 12 scientific articles: 25 publications for pharmaceutical services (pharmacy procedures to ensure participant safety from investigational product ordering to final disposition), 14 for Quality Indicators, 12 for Human Resources, 11 for Infrastructure, 11 for Material Resources and 5 for Investigational Product. Our results synthesize information for the organization, operation and evaluation of CTP in Brazil, emphasizes the inclusion of the pharmacist within the clinical trials context, and contributes to preparation for monitoring, auditing, and inspections conducted by regulatory agencies.

O desenvolvimento de novos medicamentos depende de etapas científicas que culminam nos ensaios clínicos em seres humanos. A farmácia de ensaios clínicos (FEC) é o local destinado ao recebimento, preparação, armazenamento e dispensação do produto investigacional (PI). Para tanto, deve possuir infraestrutura e procedimentos que garantam a segurança do participante e a qualidade da pesquisa. Este trabalho teve por objetivo sistematizar diretrizes para FEC no Brasil. Foi realizada uma revisão de escopo e as diretrizes foram organizadas utilizando o método de Ishikawa ("método 6Ms"). No total foram selecionadas 51 publicações, sendo 39 diretrizes e normas e 12 artigos científicos para cada "M"; 25 descreveram o ciclo de assistência farmacêutica (procedimentos para assegurar a segurança dos participantes, desde a requisição do produto até a destinação final), 14 indicadores de qualidade, 12 de recursos humanos, 11 de infraestrutura e recursos materiais e 5 descreveram PIs. para organização, funcionamento e avaliação de FEC no Brasil e corroboram a necessidade da presença do profissional farmacêutico no ciclo da assistência farmacêutica no contexto dos ensaios clínicos, contribuindo ainda na preparação para monitorias, auditorias e inspeções de agências regulatórias.

HIV knowledge and its correlation with the Undetectable = Untransmittable slogan in Brazil

ABSTRACT Knowledge about HIV transmission and prevention is a necessary step for adopting preventive behaviors. We assessed HIV knowledge and its correlation with the perceived accuracy of the "Undetectable = Untransmittable" (U=U) slogan in an online sample with 401 adult Brazilians. Overall, 28% of participants showed high HIV knowledge level. The perceived accuracy of the U=U slogan significantly correlated with HIV knowledge. Younger participants, those reporting lower income or lower education, or who had never tested for HIV showed poorer HIV knowledge. Filling gaps of knowledge among specific populations is urgent in order to increase preventive behaviors and decrease HIV stigma.

Mortality in patients with HIV-1 and tuberculosis co-infection in Rio de Janeiro, Brazil - associated factors and causes of death.

BACKGROUND: Tuberculosis is the most frequent opportunistic infection and the leading cause of death among persons living with HIV in several low and middle-income countries. Mortality rates during tuberculosis treatment and death causes among HIV-1/TB co-infected patients may differ based on the immunosuppression severity, timing of diagnosis and prompt initiation of tuberculosis and antiretroviral therapy. METHODS: This was a retrospective observational study conducted in the clinical cohort of patients with HIV-1/Aids of the National Institute of Infectious Diseases Evandro Chagas, Rio de Janeiro, Brazil. All HIV-1 infected patients who started combination antiretroviral therapy up to 30 days before or within 180 days after the start of tuberculosis treatment from 2000 to 2010 were eligible. Causes of death were categorized according to the "Coding Causes of Death in HIV" (CoDe) protocol. The Cox model was used to estimate the hazard ratio (HR) of selected mortality variables. RESULTS: A total of 310 patients were included. Sixty-four patients died during the study period. Mortality rate following tuberculosis treatment initiation was 44 per 100 person-years within the first 30 days, 28.1 per 100 person-years within 31 and 90 days, 6 per 100 person-years within 91 and 365 days and 1.6 per 100 person-years after 365 days. Death probability within one year from tuberculosis treatment initiation was approximately 13%. In the adjusted analysis the associated factors with mortality were: CD4 ≤ 50 cells/mm3 (HR: 3.10; 95% CI: 1.720 to 5.580; p = 0.00); mechanical ventilation (HR: 2.81; 95% CI: 1.170 to 6.760; p = 0.02); and disseminated tuberculosis (HR: 3.70; 95% CI: 1.290 to 10.590, p = 0.01). Invasive bacterial disease was the main immediate cause of death (46.9%). CONCLUSION: Our results evidence the high morbidity and mortality among patients co-infected with HIV-1 and tuberculosis in Rio de Janeiro, Brazil. During the first year following tuberculosis diagnosis, mortality was the highest within the first 3 months, being invasive bacterial infection the major cause of death. In order to successfully intervene in this scenario, it is utterly necessary to address the social determinants of health contributing to the inequitable health care access faced by this population.

Incidence of antiretroviral adverse drug reactions in pregnant women in two referral centers for HIV prevention of mother-to-child-transmission care and research in Rio de Janeiro, Brazil

Mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) infection remains an important cause of new HIV infections worldwide, especially in low and middle-resource limited countries. Safety data from studies involving pregnant women and prenatal antiretroviral (ARV) exposure are still needed once these studies are often small and with a limited duration to assess adverse drug reactions (ADR). The aim of this study was to estimate the incidence of ADR related to the use of antiretroviral therapy (ART) in pregnant women in two referral centers in Rio de Janeiro State. A prospective study was carried out from February 2005 to May 2006. Women were classified according to their ART status during pregnancy diagnosis: ARV-experienced (ARTexp) or ARV-naïve (ARTn). Two hundred fourteen HIV-infected pregnant women were included: 36 ARTexp and 178 ARTn. ARTexp women have not experienced ADR. Among ARTn, 20.2% presented ADR. Incidence rate of ADR was 70.8 per 1000 person-months and the most common ADRs observed were: gastrointestinal (belly or abdominal cramps, diarrhea, nausea and vomit) in 16.3%, cutaneous (pruritus and rash) in 6.2%, anemia (2.2%) and hepatitis (1.7%). The frequency of obstetrical complications, pre-term delivery, low birth weight and birth abnormalities was low in this population. ADRs ranged from mild to moderate intensity, none of them being potentially fatal. Only in a few cases it was necessary to discontinue ART. In conclusion, the high effectiveness of ARV for HIV prevention of MTCT (PMTCT) overcomes the risk of ADR.

Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in HIV-positive pregnant women.

A lopinavir-ritonavir (LPV/r)-based regimen is recommended during pregnancy to reduce the risk of HIV mother-to-child transmission, but the appropriate dose is controversial. We compared the pharmacokinetics of standard and increased LPV/r doses during pregnancy. This randomized, open-label prospective study enrolled 60 pregnant women between gestational weeks 14 and 30. The participants received either the standard dose (400/100 mg twice a day [BID]) or increased dose (600/150 mg BID) of LPV/r tablets during pregnancy and the standard dose for 6 weeks after childbirth. Pharmacokinetics analysis was performed using a high-performance liquid chromatography-tandem mass spectrometry method. Adherent participants who received the standard dose presented minimum LPV concentrations of 4.4, 4.3, and 6.1 µg/ml in the second and third trimesters and postpartum, respectively. The increased-dose group exhibited values of 7.9, 6.9, and 9.2 µg/ml at the same three time points. Although LPV exposure was significantly higher in the increased-dose group, the standard dose produced therapeutic levels of LPV against wild-type virus in all adherent participants, except one patient in the third trimester; 50%, 37.5%, and 25%, and 0%, 15%, and 0% of the participants in the standard- and increased-dose groups failed to achieve therapeutic levels against resistant viruses during the second and third trimesters and after childbirth, respectively. After 12 weeks of treatment and after childbirth, all adherent participants achieved undetectable HIV viral loads, and their babies (49/54) were uninfected. No serious drug-related adverse events were observed. We conclude that the standard dose is appropriate for use during pregnancy and that an increased dose may be necessary for women harboring resistant HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT00605098.).

Incidence of antiretroviral adverse drug reactions in pregnant women in two referral centers for HIV prevention of mother-to-child-transmission care and research in Rio de Janeiro, Brazil.

Mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) infection remains an important cause of new HIV infections worldwide, especially in low and middle-resource limited countries. Safety data from studies involving pregnant women and prenatal antiretroviral (ARV) exposure are still needed once these studies are often small and with a limited duration to assess adverse drug reactions (ADR). The aim of this study was to estimate the incidence of ADR related to the use of antiretroviral therapy (ART) in pregnant women in two referral centers in Rio de Janeiro State. A prospective study was carried out from February 2005 to May 2006. Women were classified according to their ART status during pregnancy diagnosis: ARV-experienced (ARTexp) or ARV-naïve (ARTn). Two hundred fourteen HIV-infected pregnant women were included: 36 ARTexp and 178 ARTn. ARTexp women have not experienced ADR. Among ARTn, 20.2% presented ADR. Incidence rate of ADR was 70.8 per 1000 person-months and the most common ADRs observed were: gastrointestinal (belly or abdominal cramps, diarrhea, nausea and vomit) in 16.3%, cutaneous (pruritus and rash) in 6.2%, anemia (2.2%) and hepatitis (1.7%). The frequency of obstetrical complications, pre-term delivery, low birth weight and birth abnormalities was low in this population. ADRs ranged from mild to moderate intensity, none of them being potentially fatal. Only in a few cases it was necessary to discontinue ART. In conclusion, the high effectiveness of ARV for HIV prevention of MTCT (PMTCT) overcomes the risk of ADR.

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: 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-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.