Regina Kuhmmer

Dietary intervention prevents dyslipidemia associated with highly active antiretroviral therapy in human immunodeficiency virus type 1-infected individuals: a randomized trial.

OBJECTIVES The purpose of this study was to evaluate the efficacy of dietary intervention on blood lipids of human immunodeficiency virus (HIV)-1-infected patients who are started on highly active antiretroviral therapy (HAART). BACKGROUND Current guidelines recommend diet as first-step intervention for HIV-1-infected individuals with HAART-related dyslipidemia, but there is no evidence from randomized trials to support this recommendation. METHODS Eighty-three HIV-1-infected patients, naive from HAART, were randomly assigned to HAART with dietary intervention (diet group, n = 43) or HAART without dietary intervention (control group, n = 40) for 12 months. Diet, according to the National Cholesterol Education Program, was given every 3 months. Before and after intervention, 24-h food records and lipid profile were obtained. Data were analyzed by intention to treat, using mixed-effects models. RESULTS Diet resulted in reduction of percentage of fat intake (from 31 ± 7% to 21 ± 3% of calories), while controls presented no change in percentage of fat intake. Plasma cholesterol (from 151 ± 29 mg/dl to 190 ± 33 mg/dl) and low-density lipoprotein cholesterol (from 85 ± 24 mg/dl to 106 ± 31 mg/dl) increased in the control group and were unchanged in the diet group. Plasma triglycerides were reduced by diet (from 135 ± 67 mg/dl to 101 ± 42 mg/dl) and increased in the control group (from 134 ± 70 mg/dl to 160 ± 76 mg/dl). After 1-year follow-up, 21% of patients who received diet had lipid profile compatible with dyslipidemia compared with 68% (p < 0.001) of controls. CONCLUSIONS Among HIV-1-positive individuals naive of previous treatment, diet prevents dyslipidemia associated with HAART. (Effect of Nutritional Intervention on the Lipid Profile of HIV-Positive Patients Who Start HAART: a Randomized Trial; NCT00429845).

Dyslipidemia in HIV-infected individuals.

Metabolic complications continue to play a major role in the management of HIV infection. Dyslipidemia associated with HIV infection and with the use of combined antiretroviral therapy includes elevations in triglycerides, reduced high-density cholesterol, and variable increases in low-density and total cholesterol. The association between dyslipidemia and specific antiretroviral agents has been underscored. Multiple pathogenic mechanisms by which HIV and antiretroviral agents lead to dyslipidemia have been hypothesized, but they are still controversial. The potential clinical and pathological consequences of HIV-associated hyperlipidemia are not completely known, but several studies reported an increased risk of coronary artery disease in HIV-positive individuals receiving combined antiretroviral therapy. HIV-infected persons who have hyperlipidemia should be managed similarly to those without HIV infection in accordance with the National Cholesterol Education Program. Life style changes are the primary target. Statins and fibrates and/or modification in antiretroviral therapy are possible approaches to this problem.

Genetic polymorphisms in estrogen receptors and sexual dimorphism in fat redistribution in HIV-infected patients on HAART.

Objective:To investigate genetic single nucleotide polymorphisms (SNPs) in estrogen receptor-&agr; (ER&agr;) (ESR1, rs2234693, rs1801132, rs7757956 and rs2813544) and ER&bgr; (ESR2, rs3020450, rs7154455 and rs4986938) genes and relate them to the adverse effects lipodystrophy, dyslipidemia and metabolic syndrome as well as to differences in their prevalence between sexes in HIV-infected individuals on HAART. Design:Cross-sectional study. Methods:Blood samples and anthropometric measurements were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas and Rio Grande in Brazil. The SNPs were genotyped by real-time PCR. Results:The lipodystrophy subtype frequencies in patients of different sexes showed statistically significant differences; the atrophic pattern was more prevalent in men, and the hypertrophic pattern was more prevalent in women. Furthermore, metabolic syndrome prevalence was higher in women than in men. The ESR1 rs2813544 G-allele was associated with higher measurements of several anthropometric variables in women: BMI, total subcutaneous fat and subcutaneous fat of limbs. Additionally, patients who were AA homozygous for ESR2 rs3020450 presented an increased risk for developing lipoatrophy (prevalence ratio 1.37, 95% confidence interval 1.09–1.73, P = 0.007). Conclusion:Significant differences in lipodystrophy and metabolic syndrome prevalence were detected between sexes. Moreover, the ESR1 gene (rs2813544) presented significant sex-specific associations with anthropometric variables, and the ESR2 gene (rs3020450) was associated with an increased risk of developing lipoatrophy. Our results suggest that these genes are in part responsible for the sexual dimorphism in fat tissue redistribution and patterns of lipodystrophy.

The role of mannose-binding lectin gene polymorphisms in susceptibility to HIV-1 infection in Southern Brazilian patients.

Objective:This study investigates the role of mannose-binding lectin (MBL) in the susceptibility to HIV-1 infection analyzing polymorphisms located at the MBL2 promoter and exon 1 regions. Materials and methods:The prevalence of MBL2 variant alleles was investigated in 410 HIV-1-infected patients from the South Brazilian HIV cohort and in 345 unexposed uninfected healthy individuals. The promoter variants were genotyped using polymerase chain reaction with sequence-specific primers (PCR-SSP) and exon 1 variants were analyzed by real-time PCR using a melting temperature assay and were confirmed by PCR-restriction fragment length polymorphism (RFLP). MBL2 genotypic and allelic frequencies were compared between HIV-1-infected patients and controls using the chi-squared tests. Results:The analyses were performed subdividing the individuals according to their ethnic origin. Among Euro-derived individuals a higher frequency of the LX/LX genotype was observed in patients when compared to controls (P < 0.001). The haplotypic analysis also showed a higher frequency of the haplotypes associated with lower MBL levels among HIV-1-infected patients (P = 0.0001). Among Afro-derived individuals the frequencies of LY/LY and HY/HY genotypes were higher in patients when compared to controls (P = 0.009 and P = 0.02). Conclusions:An increased frequency of MBL2 genotypes associated with low MBL levels was observed in Euro-derived patients, suggesting a potential role for MBL in the susceptibility to HIV-1 infection in Euro-derived individuals.

SNPs in the APM1 gene promoter are associated with adiponectin levels in HIV-infected individuals receiving HAART.

Objective: This study aimed to investigate the association between 4 polymorphisms in the leptin, leptin receptor, and adiponectin (APM1) genes and the occurrence of lipodystrophy and dyslipidemia in HIV-infected patients receiving highly active antiretroviral therapy (HAART). Materials and Methods: Genotypes of 410 HIV-infected patients on HAART were investigated. Anthropometric (weight, height, waist circumference and skinfolds thickness) and biochemical (blood lipids, glucose, leptin, and adiponectin levels) parameters were evaluated. Genotype frequencies were compared between patients with or without lipodystrophy. Mean biochemical and anthropometric parameters were compared between the different genotypes. Results: Lipodystrophy prevalence was 53.4%. Genotype frequencies were not different between patients with or without lipodystrophy. Carriers of the A allele for the APM1-11391 G>A and of the C allele for APM1-11377 C>G presented higher adiponectin levels compared to other genotypes, and carriers of the -11391A-11377C haplotype when compared with carriers of other haplotypes. Conclusions: SNPs in APM1 gene are associated with adiponectin levels in HIV-infected patients receiving HAART and may thus affect the occurrence of metabolic alterations in these patients. No influence of the leptin and leptin receptor gene polymorphisms on the occurrence of lipodystrophy and dyslipidemia was observed.

Genetic Markers Associated to Dyslipidemia in HIV-Infected Individuals on HAART

This study evaluated the impact of 9 single nucleotide polymorphisms (SNPs) in 6 candidate genes (APOB, APOA5, APOE, APOC3, SCAP, and LDLR) over dyslipidemia in HIV-infected patients on stable antiretroviral therapy (ART) with undetectable viral loads. Blood samples were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas, and Rio Grande in Brazil. The SNPs were genotyped by conventional polymerase chain reaction (PCR) and real-time PCR. The prevalence of dyslipidemia was particularly high among the protease inhibitors-treated patients (79%). APOE (rs429358 and rs7412) genotypes and APOA5 −1131T>C (rs662799) were associated with plasma triglycerides (TG) and low-density-lipoprotein cholesterol levels (LDL-C). The APOA5 −1131T>C (rs662799) and SCAP 2386A>G (rs12487736) polymorphisms were significantly associated with high-density-lipoprotein cholesterol levels. The mean values of the total cholesterol and LDL-C levels were associated with both the APOB SP Ins/Del (rs17240441) and APOB XbaI (rs693) polymorphisms. In conclusion, our data support the importance of genetic factors in the determination of lipid levels in HIV-infected individuals. Due to the relatively high number of carriers of these risk variants, studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen.

Endosomal toll-like receptor gene polymorphisms and susceptibility to HIV and HCV co-infection – Differential influence in individuals with distinct ethnic background

The genetic background of human populations can influence the susceptibility and outcome of infection diseases. Toll-like receptors (TLRs) have been previously associated with susceptibility to human immunodeficiency virus (HIV) infection, disease progression and hepatitis C, virus (HCV) co-infection in different populations, although mostly in Europeans. In this study, we investigated the genetic role of endosomal TLRs on susceptibility to HIV infection and HCV co-infection through the analysis of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and TLR9 rs352140 polymorphisms in 789 Brazilian individuals (374 HIV+ and 415 HIV-), taking into account their ethnic background. Amongst the 357 HIV+ individuals with available data concerning HCV infection, 98 were positive. In European descendants, the TLR9 rs5743836 C carriers displayed a higher susceptibility to HIV infection [dominant, Odds Ratio (OR)=1.53; 95% CI: 1.05-2.23; P=0.027]. In African descendants, TLR9 rs5743836 CT genotype was associated with protection to HIV infection (codominant, OR=0.51; 95% CI: 0.30-0.87; P=0.013). Also, the TLR9 rs352140 AA variant genotype was associated with susceptibility to HIV+/HCV+ co-infection in African descendants (recessive, OR=2.92; 95% CI: 1.22-6.98, P=0.016). These results are discussed in the context of the different ethnic background of the studied individuals highlighting the influence of this genetic/ethnic background on the susceptibility to HIV infection and HIV/HCV co-infection in Brazilian individuals.

Polymorphisms in adiponectin receptor genes are associated with lipodystrophy-related phenotypes in HIV-infected patients receiving antiretroviral therapy

Adiponectin is a circulating peptide secreted by mature adipocytes that may act as a regulator of glucose and lipid metabolism. This study aimed to investigate the association between genetic variability in the adiponectin receptor genes ADIPOR1 (adiponectin receptor 1) and ADIPOR2 and lipodystrophy and its related anthropometric and metabolic phenotypes in HIV‐infected patients on highly active antiretroviral therapy (HAART).

CCR5Δ32 in HCV infection, HCV/HIV co-infection, and HCV-related diseases

Although a potential involvement of the CCR5Δ32 variant has already been suggested in relation to susceptibility to hepatitis C virus (HCV) infection, data from the literature is still quite controversial. Thus, our study evaluated the influence of the CCR5Δ32 allele variant in HCV infection, HCV/HIV co-infection, and HCV-related diseases in individuals from southern Brazil. A total of 1352 individuals were included in this study, divided into the following groups: Control (n = 274); HCV+ (n = 674); HIV+ (n = 300); HCV+/HIV+ (n = 104). Individuals from the HCV+ group were further stratified according to clinical/histological criteria, as HCV+/control (n = 124); HCV+/fibrosis (n = 268); HCV+/cirrhosis (n = 190); HCV+/hepatocarcinoma (n = 92). Considering all individuals included in this study, the following genotype frequencies were observed: wild-type homozygous (wt/wt), 88.76%; heterozygous (wt/Δ32), 10.72%; variant homozygous (Δ32/Δ32), 0.52%. Genotypic frequencies were very similar between the groups. Of note, the frequency of the Δ32 homozygous was quite similar comparing control uninfected against the HCV+ individuals (p > 0.999). The overall Δ32 allele frequency was estimated at 5.88%. Considering the number of Δ32 allele carriers and non-carriers, no statistically significant differences (p > 0.05) between the groups were observed, suggesting that the CCR5Δ32 variant does not influence the susceptibility to HCV infection, HCV/HIV co-infection, or HCV-related diseases in individuals from southern Brazil.

Reuse of disposable syringes and needles in patients with type 2 diabetes

Results From October 2014 to January 2015, we included 28 participants. Fifteen (54%) were female, average age was 67 (SD 14) yrs. and average BMI was 30 kg/m2 (SD 8). Household monthly income was less than R