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.

Cardiovascular disease among people living with HIV in Brazil.

OBJECTIVES: There is a paucity of data on cardiovascular disease (CVD) among people living with HIV (PLHIV) in resource-limited countries. We assessed factors associated with CVD and the impact of prevalent CVD on all-cause mortality in PLHIV on antiretroviral therapy in Brazil. METHODS: Competing risk regression to assess factors associated with CVD and all-cause mortality in the HIV-Brazil Cohort Study between 2003 and 2014. RESULTS: Among 5614 patients, the rate of CVD was 3.5 (95% confidence interval [95% CI] 2.9-4.3) per 1000 person-years. CVD was associated with older age (adjusted hazard ratio [aHR] 6.4 for ≥55 years vs. <35 years, 95% CI: 2.5-16.3, P < 0.01), black race (aHR 1.8 vs. white race, 95% CI: 1.0-3.1, P = 0.04), past CVD (aHR 3.0 vs. no past CVD, 95% CI: 1.4-6.2, P < 0.01), hypertension (aHR 1.8 vs. no hypertension, 95% CI: 1.0-3.1, P = 0.04), high-grade dyslipidemia (aHR 9.3 vs. no high-grade dyslipidemia, 95% CI: 6.0-14.6, P < 0.01), ever smoking (aHR 2.4 vs. never, 95% CI: 1.2-5.0, P = 0.02) and low nadir CD4 cell count (aHR 1.8 for 100-250 cells/mm3 vs. >250 cells/mm3 , 95% CI: 1.0-3.2, P = 0.05). The rate of death was 16.6 (95% CI: 15.1-18.3) per 1000 person-years. Death was strongly associated with having had a past CVD event (aHR 1.7 vs. no past CVD event, 95% CI: 1.1-2.7, P = 0.01). CONCLUSIONS: Traditional and HIV-specific factors associated with CVD among PLHIV in Brazil are similar to those identified among PLHIV in high-income countries. PLHIV in Brazil with a history of CVD have a high risk of death. CVD care and treatment remain priorities for PLHIV in Brazil as this population ages and antiretroviral therapy use expands.

OBJECTIFS: Il existe peu de données sur les maladies cardiovasculaires (MCV) chez les personnes vivant avec le VIH (PVVIH) dans les pays à ressources limitées. Nous avons évalué les facteurs associés aux MCV et l'impact des MCV prévalentes sur la mortalité toutes causes confondues des PVVIH sous le traitement antirétroviral au Brésil. MÉTHODES: Régression des risques concurrente pour évaluer les facteurs associés aux MCV et à la mortalité toutes causes confondues dans l'étude de cohorte VIH-Brésil entre 2003 et 2014. RÉSULTATS: Parmi 5.614 patients, le taux de MCV était de 3,5 (intervalle de confiance à 95% [IC95%] 2,9-4,3) pour 1.000 personnes-années. Les MCV étaient associées à un âge plus avancé (rapport de risque ajusté [aHR] 6,4 chez les ≥55 ans versus chez les <35 ans, IC95%: 2,5-16,3 ; p <0,01), race noire (aHR: 1,8 versus race blanche, IC95%: 1,0-3,1 ; p = 0,04), MCV passée (aHR: 3,0 versus pas de MCV passée, IC95%: 1,4-6,2 ; p <0,01), hypertension (aHR: 1,8 versus pas d'hypertension, IC95%: 1,0-3,1 ; p = 0,04), dyslipidémie de grade élevé (aHR 9,3 versus absence de dyslipidémie de grade élevé, IC95%: 6,0-14,6 ; p <0,01), tabagisme (aHR 2,4 versus n'avoir jamais fumé, IC95%: 1,2-5,0 ; p = 0,02) et faible nombre de CD4 au nadir (aHR: 1,8 pour 100-250 cellules/mm3 versus >250 cellules/mm3 , IC95%: 1,0-3,2 ; p = 0,05). Le taux de décès était de 16,6 (IC95%: 15,1-18,3) pour 1.000 personnes-années. Le décès était fortement associé à un événement MCV antérieur (aHR: 1,7 versus aucun événement MCV antérieur, IC95%: 1,1-2,7 ; p = 0,01). CONCLUSIONS: Les facteurs traditionnels et spécifiques au VIH associés aux MCV chez les PVVIH au Brésil sont similaires à ceux identifiés chez les PVVIH dans les pays à revenu élevé. Les PVVIH au Brésil ayant des antécédents de MCV ont un risque élevé de décès. Les soins et le traitement des MCV restent des priorités pour les PVVIH au Brésil à mesure que cette population vieillit et que l'utilisation des thérapies antirétrovirales augmente.

Biochemical non-invasive assessment of liver fibrosis cannot replace biopsy in HIV-HCV coinfected patients.

BACKGROUND AND RATIONALE: The liver biopsy has been considered the gold standard for the diagnosis and quantification of fibrosis. However, this method presents limitations. In addition, the non-invasive evaluation of liver fibrosis is a challenge. The aim of this study was to validate the fibrosis cirrhosis index (FCI) index in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, and compare to AST/ALT ratio (AAR), AST to platelet ratio index (APRI) and FIB-4 scores, as a tool for the assessment of liver fibrosis in coinfected patients. MATERIAL AND METHODS: Retrospective cross sectional study including 92 HIV-HCV coinfected patients evaluated in two reference centers for HIV treatment in the Public Health System in Southern Brazil. Patients who underwent liver biopsy for any indication and had concomitant laboratory data in the 3 months prior to liver biopsy, to allow the calculation of studied noninvasive markers (AAR, APRI, FIB-4 and FCI) were included. RESULTS: APRI < 0.5 presents the higher specificity to detect no or minimal fibrosis, whereas APRI > 1.5 presents the best negative predictive value and FCI > 1.25 the best specificity to detect significant fibrosis. The values of noninvasive markers for each Metavir fibrosis stage showed statistically significant differences only for APRI. In conclusion, until better noninvasive markers for liver fibrosis are developed and validated for HIV-HCV coinfected patients, noninvasive serum markers should be used carefully in this population.

Association of blood pressure and hypertension with alcohol consumption in HIV-infected white and nonwhite patients.

INTRODUCTION: Although alcohol abuse is associated with hypertension in whites and nonwhites, it has been scarcely investigated in HIV-infected patients. OBJECTIVE: To investigate whether the association of alcohol abuse with hypertension is influenced by skin color in HIV-infected individuals. METHODS: Cross-sectional study in HIV-infected individuals aged 18 years or older. Demographic characteristics, lifestyle, and HIV infection were investigated. Alcohol abuse was defined as ≥ 15 (women) and ≥ 30 g/alcohol/day (men), and binge drinking by the intake of ≥ 5 drinks on a single occasion. Hypertension was defined by blood pressure ≥ 140/90 mmHg or use of blood pressure-lowering agents. RESULTS: We studied 1,240 individuals, with 39.1 ± 10 years, 51% males and 57% whites. Age and body mass index were associated with blood pressure, and there was an independent association of alcohol abuse with hypertension in whites (RR = 1.9, 95% CI 1.1-3.3) and nonwhites (RR = 2.4, 95% CI 1.4 to 4.0). Among nonwhite individuals who were alcohol abusers, systolic (9.3 ± 3.2; P = 0.001) and diastolic blood pressures (6.4 ± 2.1; P = 0.008) were higher than in nonabusers. CONCLUSION: Alcohol abuse is a risk factor for hypertension in white and nonwhite HIV-infected individuals. The association of ethanol consumption with blood pressure is not explained by AIDS-related conditions.

Risk of coronary heart disease among HIV-infected patients: a multicenter study in Brazil.

Cardiovascular disease has emerged as a crescent problem among HIV-infected population. This study aimed to determine the 10-year risk of coronary heart disease using the Framingham risk score among HIV-infected patients from three regions of Brazil. This is a pooled analysis of three cohort studies, which enrolled 3,829 individuals, 59% were men, 66% had white skin color, and mean age 39.0 ± 9.9 years. Comparisons among regions showed that there were marked differences in demographic, socioeconomic, clinical, and HIV-related characteristics. Prevalence of Framingham score ≥10 was 4.5% in the Southern, 4.2% in the Midwest, and 3.9% in the Northeast of Brazil. The Framingham score ≥10 was similar between regions for males, patients aged ≥60 years, with obesity, central obesity, hypertension, and diabetes mellitus. Women were three times more likely to have coronary heart disease in 10 years than men. Hypertension and diabetes increased more than four times the risk of coronary heart disease, followed by central obesity, obesity, and prehypertension. The use of antiretroviral agents and time since HIV diagnosis were not risk factors for coronary artery disease in 10 years. In conclusion, hypertension and diabetes are the strongest independent predictors of 10-year risk of coronary heart disease among HIV-infected population.

Metabolic syndrome and population attributable risk among HIV/AIDS patients: comparison between NCEP-ATPIII, IDF and AHA/NHLBI definitions.

BACKGROUND: Metabolic Syndrome (MetS) is based on the same individual components, but has received several amendments to the original definition. In this study, we verified the prevalence of metabolic syndrome according to different criteria, and the impact of each component on the diagnostic. METHODS: This cross-sectional study enrolled HIV infected patients from a HIV/AIDS reference Center in southern Brazil. Metabolic syndrome was identified according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATPIII), the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) criteria, and using a standardized questionnaire and blood testing. RESULTS: A sample of 1240, out of 1295, HIV-infected patients was enrolled. Males were on average older, more educated, and had shorter time since the HIV diagnosis. The population attributable risk (PAR) for waist circumference explained 80% of the prevalence among men and women (AHA/NHLBI criteria). Triglycerides had the highest impact on prevalence of metabolic syndrome according to all criteria, independently of age, skin color and HAART use, among men. CONCLUSIONS: In this large sample of HIV infected patients, the overall prevalence of metabolic syndrome, under either classification, was noticeable and the AHA/NHLBI definition accounted for the highest prevalence.

Antiretroviral therapy and Kaposi's sarcoma trends and outcomes among adults with HIV in Latin America.

INTRODUCTION: Kaposi's sarcoma (KS) remains the most frequent malignancy in persons living with HIV (PWH) in Latin America. We examined KS trends and outcomes from Latin American clinical sites in the era of increased access to antiretroviral therapy (ART). METHODS: Cohorts in Brazil, Peru, Mexico, Honduras, Argentina and Chile contributed clinical data of PWH ≥16 years old from 2000 to 2017, excluding patients with KS diagnosed before clinic enrolment. We compared KS incidence over time using multivariable incidence rate ratios. Predictors of KS before/at or after ART initiation and of mortality after KS were examined using Cox regression. RESULTS: Of 25 981 PWH, 481 had incident KS, including 200 ART-naïve and 281 ART-treated patients. From 2000 to 2017, the incidence of KS decreased from 55.1 to 3.0 per 1000 person-years. In models adjusting for CD4 and other factors, the relative risk for KS decreased from 2000 to 2008. Since 2010, the adjusted risk of KS increased in the periods before and ≤90 days after ART initiation but decreased >90 days after ART. In addition to low CD4 and male-to-male sex, KS risk after ART was associated with age and history of other AIDS-defining illnesses. Mortality after KS (approximately 25% after five years) was not associated with either year of KS diagnosis nor timing of diagnosis relative to ART initiation. CONCLUSIONS: KS incidence in Latin America has remained stable in recent years and risk is highest before and shortly after ART initiation. Early diagnosis of HIV and ART initiation remain critical priorities in the region.

Trends and predictors of non-communicable disease multimorbidity among adults living with HIV and receiving antiretroviral therapy in Brazil.

INTRODUCTION: People living with HIV (PLHIV) on antiretroviral therapy (ART) experience high rates of non-communicable diseases (NCDs). These co-morbidities often accumulate and older adults may suffer from multimorbidity. Multimorbidity has been associated with loss of quality of life, polypharmacy, and increased risk of frailty and mortality. Little is known of the trends or predictors NCD multimorbidity in PLHIV in low- and middle-income countries. METHODS: We examined NCD multimorbidity in adult PLHIV initiating ART between 2003 and 2014 using a multi-site, observational cohort in Brazil. NCDs included cardiovascular artery disease, hyperlipidemia (HLD), diabetes, chronic kidney disease, cirrhosis, osteoporosis, osteonecrosis, venous thromboembolism and non-AIDS-defining cancers. Multimorbidity was defined as the incident accumulation of two or more unique NCDs. We used Poisson regression to examine trends and Cox proportional hazard models to examine predictors of multimorbidity. RESULTS: Of the 6206 adults, 332 (5%) developed multimorbidity during the study period. Parallel to the ageing of the cohort, the prevalence of multimorbidity rose from 3% to 11% during the study period. Older age, female sex (adjusted hazard ratio (aHR) = 1.30 (95% confidence interval (CI) 1.03 to 1.65)) and low CD4 nadir (<100 vs. ≥200 cells/mm3 aHR = 1.52 (95% CI: 1.15 to 2.01)) at cohort entry were significantly associated with increased risk of multimorbidity. Among patients with incident multimorbidity, the most common NCDs were HLD and diabetes; however, osteoporosis was also frequent in women (16 vs. 35% of men and women with multimorbidity respectively). CONCLUSIONS: Among adult PLHIV in Brazil, NCD multimorbidity increased from 2003 to 2014. Females and adults with low CD4 nadir were at increased risk in adjusted analyses. Further studies examining prevention, screening and management of NCDs in PLHIV in low- and middle-income countries are needed.

People living with HIV on ART have accurate perception of lipodystrophy signs: a cross-sectional study.

BACKGROUND: The prevalence of lipodystrophy ranges from 31 to 65%, depending on the criteria adopted for diagnosis. The usual methods applied in the diagnosis vary from self-perception, medical examination, skinfolds measurements, or even imaging assessment for confirmation of fat distribution changes. Although several methods have been developed, there is no gold standard for characterization of LA and LH, or mixed forms. This study aimed to compare self-reported signs of lipodystrophy with objective measures by skinfolds and circumferences, and to evaluate the prevalence of lipoatrophy (LA) and lipohypertrophy (LH) among subjects living with HIV/AIDS on ART. METHODS: A cross-sectional study enrolled participants living with HIV/AIDS receiving ART, aged 18 years or older from an outpatient health care center, in Southern Brazil. Self-reported body fat enlargement in the abdomen, chest or breasts, and dorsocervical fat pad were used to determine LH, while LA was identified by self-reported fat wasting of the face, neck, legs, arms or buttocks. Measurements were obtained with a scientific caliper for infraorbital, buccal, and submandibular skinfolds, and using an inelastic tape to measure circumferences of waist, hip, neck, and arm. LH and LA were established by the presence of at least one self-reported sign. RESULTS: Comparisons of self-reported signs with objective measurements for men and women were carried out in 815 participants on ART, out of 1240 participants with HIV infection. Self-report of decreased facial fat and sunken cheeks was associated with lower infraorbital, buccal, and submandibular skinfolds. Participants who reported buffalo hump had, on average, greater neck circumference, as well as those who have increased waist circumference also reported abdominal enlargement, but no buttock wasting. Men were most commonly affected by lipoatrophy (73 vs. 53%; P < 0.001), and women by lipohypertrophy (79 vs. 56%; P < 0.001). CONCLUSION: In conclusion, self-reported signs of lipodystrophy and lipoatrophy are prevalent, differ by gender, and are associated with objective measurements in people living with HIV/AIDS.

Alcohol Drinking Pattern: A Comparison between HIV-Infected Patients and Individuals from the General Population.

BACKGROUND: Alcohol consumption is highly prevalent in the general population and among HIV-infected population. This study aimed to compare the pattern of alcohol consumption and to describe characteristics associated with heavy alcohol consumption in individuals from the general population with patients infected with HIV. METHODS: Participants for this analysis came from a population-based cross-sectional study and from a consecutive sampling of patients infected with HIV. Participants aged 18 years or older were interviewed using similar questionnaires with questions pertaining to socio-demographic characteristics, alcohol consumption, smoking, physical activity, and HIV-related characteristics, among others. Blood pressure and anthropometric measures were measured using standardized procedures. RESULTS: Weekly alcohol consumption was more prevalent among individuals from the general population than HIV-infected patients: 57.0 vs. 31.1%, P<0.001. The prevalence of heavy episodic drinking was higher in the population sample as well: 46.1 vs. 17.0%, P<0.001. In the general population, heavy alcohol consumption was more prevalent in men. Cigarette smoking was independently associated with heavy alcohol consumption among HIV infected (Prevalence Ratio; PR = 5.9; 95%CI 2.6-13.9; P<0,001) and general population (PR = 2.6; 95%CI 1.9-3.0; P<0.001). Years at school were inversely associated with heavy alcohol consumption among HIV-infected patients and directly associated among participants from the general population, even after controlling for sex, age, skin color, and smoking. CONCLUSIONS: Heavy alcohol consumption is more prevalent in the general population than among HIV-infected patients. Individuals aware about their disease may reduce the amount of alcoholic beverages consumption comparatively to healthy individuals from the general population.

Comparison between potential risk factors for cardiovascular disease in people living with HIV/AIDS in areas of Brazil.

INTRODUCTION: Coronary heart disease and its risk factors depend on genetic characteristics, behaviors, and habits, all of which vary in different regions. The use of antiretroviral therapy (ARV) has increased the survival of people living with HIV/AIDS (PLWHA), who begin to present mortality indicators similar to the general population. This study aimed to compare the prevalence of factors potentially associated with coronary heart disease in three cohorts of PLWHA from three different regions of Brazil. METHODOLOGY: The study population was composed of participants of the cohorts of Pernambuco, Goiás, and Rio Grande do Sul states. In these sites, adult patients attending reference centers for treatment of HIV/AIDS were consecutively enrolled. RESULTS: Pernambuco and Goiás had a higher proportion of males and of individuals with high-risk high-density lipoprotein (HDL). Pernambuco also had a greater proportion of individuals with hypertension, elevated triglycerides, and CD4 counts below 200 cells/mm(3). Lower education was more frequent in Rio Grande do Sul, and the use of cocaine was higher in this state. CONCLUSIONS: The results confirm the importance of risk factors for coronary heart disease in PLHIV and highlight differences in the three cohorts. Specific measures against smoking and sedentary lifestyle, avoidance of advanced stages of immunosuppression, and appropriate treatment of dyslipidemia and dysglicemia are urgently needed to cope with the disease in Brazil.

Physical activity: do patients infected with HIV practice? How much? A systematic review.

Several studies have suggested that aerobic physical activity is safe and beneficial for HIV-infected adults. However, there is information lacking regarding whether HIV-infected patients practice physical activity and to what extent. Therefore, the aim of this systematic review was to determine the prevalence of physical activity, sedentary lifestyle or lack of physical activity in non-experimental conditions performed by HIV-infected subjects. The electronic search was conducted using Medline and EMBASE bibliographic databases and the platforms of Bireme, Ovid, Science Direct, High Wire and SCIELO from January 1990 to July 2011. Original observational studies were included. Of the 2,838 articles found, 48 met the inclusion criteria. Following data extraction and after reading the manuscripts, 24 were selected for systematic review. Of the 24 studies, most were cross-sectional studies. The average quality score using the modified Newcastle-Ottawa scale was 2.8±1.5. The diversity of methods used to assess physical activity precluded the calculated summary estimate of prevalence. The percentage of sedentary lifestyle was determined in 13 articles which conducted studies on HIV-infected individuals. The percentage of sedentary lifestyle or physical inactivity ranged from 19%to 73%, with the level determined by different methods. In conclusion, there are few well-designed studies with adequate sample size to represent the population of HIV-infected individuals. A pooled estimate could not be calculated due to the differences in physical activity measurements and definitions of physically active and non-active HIV-infected individuals.

Independent predictors of metabolic syndrome in HIV-infected patients.

Metabolic syndrome (MetS) is associated with development of type 2 diabetes mellitus and increased risk for cardiovascular disease. However, a few studies have assessed its prevalence and risk factors among HIV patients from developing countries. The aim of this study was to identify independent risk factors for metabolic syndrome by the criteria of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) among HIV-infected men and women. A cross-sectional study enrolled patients, aged 18 years or older, who sought to confirm the diagnosis or sought treatment in the outpatient service of a public health care center in southern Brazil. From June 2006 to December 2008, certified research assistants conducted interviews using standardized questionnaires and anthropometric measurements. Fasting blood sample was collected, use of highly active antiretroviral therapy (HAART) was ascertained, and MetS was characterized by AHA/NHLBI criteria. In the total, 1240 of 1295 HIV-infected patients were included. MetS prevalence was 24.7% and was similar among men and women. Among men, age, education, physical activity, body mass index (BMI), and HAART use were independently associated with MetS, while among women, there were associations with age, BMI, and use of protease inhibitors. In conclusion, high prevalence of MetS was detected in HIV-infected men and women. In both genders, age and BMI were directly and independently associated with MetS. The association between the use of HAART and MetS was confirmed among men but not among women.

Origin and evolutionary history of HIV-1 subtype C in Brazil.

OBJECTIVE: To investigate the origin and to reconstruct the onset date of the HIV-1 subtype C epidemic in Brazil. DESIGN: Three independent datasets of subtype C sequences isolated from HIV-1-positive patients from southern Brazil over a period of 15 years (1991-2006) were analyzed: 82 env V3 sequences (213 nt), 40 env C2-C5 sequences (559 nt), and 72 pol sequences (960 nt). METHODS: Brazilian sequences were compared with other subtype C reference strains from the database using basic local alignment search tool, phylogenetic analyses, and searching of specific amino acid signature patterns. Evolutionary parameters were estimated using a Bayesian coalescent-based method under either strict or relaxed molecular clock models. RESULTS: HIV-1 subtype C sequences from Brazil and Burundi formed a monophyletic cluster at both env and pol regions and shared specific amino acid signatures in the protease region when compared with other viruses of the same subtype from around the world. All Brazilian strains arose as a monophyletic subcluster within the Burundi-Brazilian lineage, whereas isolates from Burundi appeared at the origin of the clade. Evolutionary analyses of both env and pol genomic regions indicate that the age of the most recent common ancestor of the Brazilian subtype C clade dates back to the early 1980s. CONCLUSION: The subtype C epidemic in the southern Brazilian region was initiated by the introduction of a single founder strain closely related to subtype C strains from Burundi. Our results suggest that this founder event probably took place around the early 1980s, roughly a decade before the previous estimates.