Estela Luz

A randomized, clinical trial to evaluate the impact of regular physical activity on the quality of life, body morphology and metabolic parameters of patients with AIDS in Salvador, Brazil.

Patients with AIDS under antiretroviral therapy often present with metabolic problems associated with HIV infection and its therapy, which can affect their quality of life. The knowledge on the potential benefits of regular physical exercises for HIV-infected patients is limited. Objective:We conducted a clinical trial to evaluate the impact of regular physical activity on quality of life, anatomic disturbances, and/or metabolic changes in patients with AIDS in the city of Salvador, Brazil. Methods:Patients were randomly assigned in monthly workshops (1-hour duration) to discuss the importance of physical activity and receive nutritional counseling (control group) or to receive a 1-hour supervised gym class three times a week plus monthly nutritional counseling (intervention group). Before and after intervention, body composition, maximum oxygen consumption, metabolic equivalent, blood count, fasting total cholesterol, high-density lipoprotein, triglycerides, glucose, HIV viral load and CD4/CD8 counts, and resting heart rate were measured. Quality of life was evaluated at baseline and after 24 weeks. Results:The domains of quality of life, general health, vitality and mental health increased in the exercise group (P < 0.05) compared with the control group. In the exercise group, fat mass (P = 0.04), the resting heart rate (P = 0.001), waist circumference (P = 0.002), and glucose (P = 0.003) decreased. Muscle mass (P = 0.002), CD4 + T cells (P = 0.002), metabolic equivalent (P = 0.014), and maximum oxygen consumption (P = 0.05) increased. Conclusion:The practice of regular exercise, coupled with nutritional guidance, in individuals with HIV/AIDS significantly improves the quality of life.

High Zika Virus Seroprevalence in Salvador, Northeastern Brazil Limits the Potential for Further Outbreaks

ABSTRACT During 2015 to 2016, Brazil reported more Zika virus (ZIKV) cases than any other country, yet population exposure remains unknown. Serological studies of ZIKV are hampered by cross-reactive immune responses against heterologous viruses. We conducted serosurveys for ZIKV, dengue virus (DENV), and Chikungunya virus (CHIKV) in 633 individuals prospectively sampled during 2015 to 2016, including microcephaly and non-microcephaly pregnancies, HIV-infected patients, tuberculosis patients, and university staff in Salvador in northeastern Brazil using enzyme-linked immunosorbent assays (ELISAs) and plaque reduction neutralization tests. Sera sampled retrospectively during 2013 to 2015 from 277 HIV-infected patients were used to assess the spread of ZIKV over time. Individuals were georeferenced, and sociodemographic indicators were compared between ZIKV-positive and -negative areas and areas with and without microcephaly cases. Epidemiological key parameters were modeled in a Bayesian framework. ZIKV seroprevalence increased rapidly during 2015 to 2016, reaching 63.3% by 2016 (95% confidence interval [CI], 59.4 to 66.8%), comparable to the seroprevalence of DENV (75.7%; CI, 69.4 to 81.1%) and higher than that of CHIKV (7.4%; CI, 5.6 to 9.8%). Of 19 microcephaly pregnancies, 94.7% showed ZIKV IgG antibodies, compared to 69.3% of 257 non-microcephaly pregnancies (P = 0.017). Analyses of sociodemographic data revealed a higher ZIKV burden in low socioeconomic status (SES) areas. High seroprevalence, combined with case data dynamics allowed estimates of the basic reproduction number R0 of 2.1 (CI, 1.8 to 2.5) at the onset of the outbreak and an effective reproductive number Reff of <1 in subsequent years. Our data corroborate ZIKV-associated congenital disease and an association of low SES and ZIKV infection and suggest that population immunity caused cessation of the outbreak. Similar studies from other areas will be required to determine the fate of the American ZIKV outbreak. IMPORTANCE The ongoing American Zika virus (ZIKV) outbreak involves millions of cases and has a major impact on maternal and child health. Knowledge of infection rates is crucial to project future epidemic patterns and determine the absolute risk of microcephaly upon maternal ZIKV infection during pregnancy. For unknown reasons, the vast majority of ZIKV-associated microcephaly cases are concentrated in northeastern Brazil. We analyzed different subpopulations from Salvador, a Brazilian metropolis representing one of the most affected areas during the American ZIKV outbreak. We demonstrate rapid spread of ZIKV in Salvador, Brazil, and infection rates exceeding 60%. We provide evidence for the link between ZIKV and microcephaly, report that ZIKV predominantly affects geographic areas with low socioeconomic status, and show that population immunity likely caused cessation of the outbreak. Our results enable stakeholders to identify target populations for vaccination and for trials on vaccine efficacy and allow refocusing of research efforts and intervention strategies. IMPORTANCE The ongoing American Zika virus (ZIKV) outbreak involves millions of cases and has a major impact on maternal and child health. Knowledge of infection rates is crucial to project future epidemic patterns and determine the absolute risk of microcephaly upon maternal ZIKV infection during pregnancy. For unknown reasons, the vast majority of ZIKV-associated microcephaly cases are concentrated in northeastern Brazil. We analyzed different subpopulations from Salvador, a Brazilian metropolis representing one of the most affected areas during the American ZIKV outbreak. We demonstrate rapid spread of ZIKV in Salvador, Brazil, and infection rates exceeding 60%. We provide evidence for the link between ZIKV and microcephaly, report that ZIKV predominantly affects geographic areas with low socioeconomic status, and show that population immunity likely caused cessation of the outbreak. Our results enable stakeholders to identify target populations for vaccination and for trials on vaccine efficacy and allow refocusing of research efforts and intervention strategies.

Evidence for Congenital Zika Virus Infection From Neutralizing Antibody Titers in Maternal Sera, Northeastern Brazil

ZIKV-specific neutralizing antibody titers were significantly higher in 28 mothers of children with microcephaly than in 122 controls from northeastern Brazil, suggesting an unusually strong immunological stimulus and potential utility of maternal antibody titers to corroborate congenital ZIKV infection.

Survival and Prognostic Factors for AIDS and Non-AIDS Patients with Non-Hodgkin's Lymphoma in Bahia, Brazil: A Retrospective Cohort Study

Despite the benefits of HAART, HIV-infected patients are increasingly affected by different malignancies. We compared a 5-year-period survival time and prognostic factors for HIV-1-infected individuals diagnosed with non-Hodgkin lymphomas (NHL) in a nested case-control study, with non-HIV-infected individuals in Salvador, Brazil. Survival time and prognostic factors were compared to HIV-negative patients. 31 cases (versus 63 controls) had a significantly more advanced NHL at diagnosis and lower mean CD4 count (26 cells/mm3) than controls. Mean overall survival (OS) was 35.8 versus 75.4 months, for cases and controls, respectively (P < 0.001), while mean event-free survival time (EFS) was 34.5 months for cases, versus 68.8 for controls (P = 0.002). Higher IPI, increased LDH levels, bone marrow infiltration, lower absolute lymphocyte counts (<1,000 cells/mm3), and type B symptoms were associated with a shorter survival time for cases. Although patients without poorer prognostic factors at baseline had an OS comparable to controls, the mean CD4 cell count for cases was similar for patients with favorable and nonfavorable response to therapy. Our findings suggest that HIV-1 infection is significantly associated with a shorter survival time for patients with NHL, independently of other predictive factors and of disease stage.

Raltegravir versus lopinavir/ritonavir for treatment of HIV-infected late-presenting pregnant women

Background Late-presenting pregnant women pose a challenge in the prevention of HIV-1 mother-to-child-transmission. We compared the safety and efficacy of raltegravir and lopinavir/ritonavir for this population. Methods We did a single-center, pilot, open-label, randomized trial in Brazil (N = 44). We randomly allocated late-presenting HIV-infected pregnant women (older than 18 years with a plasma HIV-1 RNA >1000 copies/mL) to receive raltegravir 400 mg twice a day or lopinavir/ritonavir 400/100 mg twice a day plus zidovudine and lamivudine (1:1). The primary endpoint was virological suppression at delivery (HIV-1 RNA <50 copies per mL), in all patients who received at least one dose of study drugs (modified intention-to-treat analysis). Missing information was treated as failure. We assessed safety in all patients. Results We enrolled and randomly assigned treatment to 33 patients (17 in raltegravir group) between June 2015 and June 2017. The study was interrupted by the IRB because a significant difference between arms was detected in an interim analysis. All patients completed follow up at delivery. At delivery, virological suppression was achieved by 13/17 (76.5%) of patients in raltegravir group, versus 4/16 (25.0%) in lopinavir/ritonavir group (RR 3.1, 95% CI: 1.3–7.4). Patients in raltegravir group had significantly higher proportion of virological suppression at 2, 4, and 6 weeks than lopinavir/ritonavir group. Adverse events were most of mild intensity, but patients in lopinavir/ritonavir group had significantly more gastrointestinal adverse events. There was neither discontinuation nor deaths in this trial. Conclusion Raltegravir might be a first-line option for treatment of HIV-infected late-presenting pregnant women.

Immune Activation, Proinflammatory Cytokines, and Conventional Risks for Cardiovascular Disease in HIV Patients: A Case-Control Study in Bahia, Brazil

Background Cardiovascular events (CVE) are an increasing cause of morbi-mortality for HIV patients. The antiretroviral therapy (ART), persistent immune activation, and life style are factors that can increase CVE for such patients. We performed a case-control study to evaluate the role of coinfections and immune markers associated with CVE. Methods We included patients under ART, with undetectable plasma viral load ≥12 months. Patients presenting any condition of risk for CVE were considered cases, and those without CVE risk conditions were controls. History of viral infections (Epstein–Barr virus, hepatitis C virus, hepatitis B virus, and cytomegalovirus), exposure to antiretroviral drugs, time since HIV diagnosis/under ART, and life style (demographics, weight, smoking, alcohol, and illicit drug use) were assessed. CD4/CD8 nadir and current counts, nadir and current CD4/CD8 ratio, immune activation markers (CD4CD38HLADR, CD8CD38HLADR), and serum levels of eight cytokines [IL-2, IL-4, IL-6, IL-10, tumoral necrosis factor-alpha (TNF-α), interferon gamma, macrophage inflammatory proteins 1 alpha, and interferon-inducing protein (IP-10)] were measured. Results Two-thirds of patients were males. Cases (N = 106) were older (52.8 vs 49.5 years, p = 0.002), had higher levels of creatinine (0.97 vs 0.87 mg/dL, p = 0.002) and IL-6 (0.67 vs 0.52 pg/mL, p = 0.04) than controls (N = 114). There was no difference between groups regarding frequency of CD4CD39HLADR+ or CD8CD38HLADR+ cells. We found a significant correlation (all patients) between increased frequency of CD4CD38HLADR+ cells and levels of IP-10 (r = 0.171, p = 0.02) and TNF-α (r = 0.187, p = 0.01). Levels of IL-6 (r = 0.235, p = 0.02), TNF-α (r = 0.267, p = 0.01), and IP-10 (r = 0.205, p = 0.04) were correlated with CD4CD38HLADR+ cells, in controls. Higher frequency of CD4CD38HLADR+ cells was also correlated with levels of IP-10 (r = 0.271, p = 0.04) in patients presenting with arterial hypertension. Frequency of CD4CD38HLADR+ cells was negatively correlated with levels of IL-2 (r = −0.639, p = 0.01) and IL-6 (r = −0.0561, p = 0.03) in patients with hypercholesterolemia. No association was detected between viral infections or smoking/alcohol use and immune activation markers. Conclusion Our results indicate IL-6 levels are associated with increased CV risk. Activated CD4+ T cells were associated with increased levels of proinflammatory cytokines.

Neoplasms-associated deaths in HIV-1 infected and non-infected patients in Bahia, Brazil

BACKGROUND HIV-infected patients are at a higher risk to develop malignancies than general population. Although AIDS-related malignancies are a common feature of late-stage disease, patients under successful antiretroviral therapy also have an increased risk for development of non-AIDS malignancies. OBJECTIVE To compare the frequency and characteristics of adults HIV-infected patients and general population who died of malignancies in Bahia, Brazil from January 2000 to December 2010. METHODS National Information System on Mortality (SIM) was searched to identify all deaths in the study period caused by malignancies in general population and in HIV patients. The frequency of malignancies in these two groups was compared. For HIV patients we also recorded the last HIV-1 RNA plasma viral load and CD4+ cells count, retrieved from oficial databases on laboratory monitoring for HIV patients. RESULTS In the study period 733,645 deaths were reported, 677,427 (92.3%) of them in individual older than 13 years. Malignancies were the cause of death in 77,174 (11.4%) of them, and 5156 (0.8%) were associated to HIV/Aids. Among deaths of HIV/Aids patients, Kaposi´s sarcoma was the most prevalent malignancy (OR: 309.7; 95% CI: 177-544), followed by non-Hodgkin lymphoma (OR: 10.1; 95% CI: 5.3-19.3), Hodgkin´s lymphoma (OR: 4.3; 95% CI: 2.2-8.4), and cranial nervous malignancies (OR: 3.3; 95% CI:1.6-7.0). HIV patients died at a significantly lower age (43.7 years), than general population (64.5 years, p < 0.0001). Patients who had a diagnosis of Aids-related malignancies had lower CD4+ cells count than those with non-AIDS relates malignancies (p = 0.04). CONCLUSION HIV infection is a clear risk fator for development of some malignancies, and is associated with early mortality, compared to general population. The level of CD4+ cells count predicts the type of malignancies causing death in this population.

Low variation in initial CD4 cell count in a HIV referral center, in Salvador, Brazil, from 2002 to 2015

Early initiation of antiretroviral therapy increases the likelihood of effective immune restoration, quality of life, and greater life expectancy for HIV-infected individuals. We evaluated the evolution of mean CD4+ cells count at diagnosis of HIV/AIDS in Salvador, Brazil from 2002 to 2015. We identified HIV/AIDS patients older than 18 years with diagnosis of HIV infection from 2002 to 2015, who had their first laboratory evaluation at Complexo Hospitalar Prof. Edgard Santos, Federal University of Bahia. Initial mean CD4+ cells count and age, over time were evaluated. A total of 1801 patients randomly selected individuals were included in the analysis. Overall mean CD4+ count at diagnosis in the whole period was 279±265, varying from 191 in 2015 to 334 in 2011. There was no improvement in the immunological status at diagnosis from 2002 to 2015. In addition, a higher frequency of CD4+ cells count<200cells/mL in the last two years was observed. This suggests that the adopted strategies for early diagnosis of HIV/AIDS in Salvador, Brazil, are still ineffective.

Frequency of adverse events associated to antiretroviral drugs in patients starting therapy in Salvador, Brazil

The increasing number of available antiretroviral drugs (ARV) for treating HIV-1 infection has promoted an amazing reduction on AIDS-associated morbidity and mortality. However, adverse events are still a frequent finding in on-treatment patients, and may have a negative impact on patient’s quality of life, adherence to therapy, and long term health problems.1 In Brazil, we have only scarce data on the frequency of such problems, and we need to better define what is the real magnitude of these problems in HIV patients initiating antiretroviral therapy. The present work is a pilot, retrospective cohort study, in which we reviewed clinical charts of 100 patients (75% males) who started ARV therapy between 2003 and 2009, in Salvador, Bahia state, Brazil. We recorded the number of ARV regimens used by each individual, and the related problems detected during patient’s follow up. Most patients (66%) were black, as expected for a city with the characteristics of Salvador. Mean age was 43 years (range 27–67 years), and 68% were infected by unprotected homosexual contact. A total of 212 different ARV regimens were used by the group during follow up period. We found a high (75%) frequency of adverse events (AE). Table 1 summarizes the main safety problems detected in the study sample (only those AE with a frequency equal or higher than 5% were described). Of note, patients older than 50 years were more likely (58%) to present AE after starting ARV therapy. Incidence of AE was the main reason for changing ARV drugs in 53% of cases. The AE significantly associated with switching therapy were neurological (34%; p = 0.02), gastrointestinal (26%; p = 0.03) and metabolic (10%; p = 0.05). Again, switching therapy was more likely to occur in older patients (aged more than 50 years) than in younger ones. In the present study, we detected a high rate of AE in patients initiating ARV therapy in the city of Salvador, similar to that found in other studies.2,3 The high frequency of Myopathy 8 (3.8%)