Risk of coronary artery disease in individuals infected with human immunodeficiency virus

Current treatment for human immunodeficiency virus (HIV) infection has improved survival and allowed infected patients to develop atherosclerotic coronary artery disease (CAD). Specific strategies to reduce cardiovascular risk in the infected population have not been developed. It is necessary to know the magnitude of cardiovascular risk in this population. OBJECTIVES: This study aimed to assess cardiovascular risk using a well-known clinical score and to investigate coronary artery calcium scoring (CACS) in this population. METHODS: This was a cross-sectional study. Adults with HIV infection were studied. Demographic, clinical and anthropometric data, serum glucose and lipids were obtained. Cardiovascular risk was calculated through Framingham risk score (FRS) and CACS. Categorical variables were compared by Chi-square or Fisher's exact test, and continuous variables were analyzed by Student t test or Mann-Whitney test. An analysis of concordance between FRS and CACS was performed using kappa statistic. RESULTS: Forty patients, aged 45.9 ± 8.1 years, were studied. Age of risk for CAD were found in 30.0 percent, hypertension in 55.0 percent, diabetes in 10.0 percent, smoking in 35.0 percent, dyslipidemia in 67.5 percent and family history of CAD in 57.5 percent. Altered levels of total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were found in 30.0 percent, 25.0 percent and 82.5 percent, respectively. HDL-cholesterol and triglycerides were altered more frequently among protease inhibitors users. The FRS classified the risk as low for 72.5 percent, moderate for 25.0 percent, and high for 2.5 percent. CACS > 0 was found in 32.5 percent of the patients, in 67.5 percent the score was low, in 17.5 percent moderate, and in 15.0 percent high. Concordance between FRS and CACS showed a kappa = 0.435. CONCLUSIONS: There is a high prevalence of risk factors for CAD in the studied population, with dyslipidemia being the most frequent. HDL-cholesterol and triglycerides were the most frequently altered factors and were associated with the use of protease inhibitors. Risk assessed by the FRS was low in most cases. CACS > 0 was found in 32.5 percent, demonstrating the need to re-evaluate the strategies for assessing cardiovascular risk in the HIV-infected population.

Lopinavir/ritonavir dosing during pregnancy in Brazil and maternal/infant laboratory abnormalities

OBJECTIVES: To describe laboratory abnormalities among HIV-infected women and their infants with standard and increased lopinavir/ritonavir (LPV/r) dosing during the third trimester of pregnancy. METHODS: We evaluated data on pregnant women from NISDI cohorts (2002-2009) enrolled in Brazil, who received at least 28 days of LPV/r during the third pregnancy trimester and gave birth to singleton infants. RESULTS: 164 women received LPV/r standard dosing [(798/198 or 800/200 mg/day) (Group 1)] and 70 increased dosing [(> 800/200 mg/day) (Group 2)]. Group 1 was more likely to have advanced clinical disease and to use ARVs for treatment, and less likely to have CD4 counts > 500 cells/mm³. Mean plasma viral load was higher in Group 2. There were statistically significant, but not clinically meaningful, differences between groups in mean AST, ALT, cholesterol, and triglycerides. The proportion of women with Grade 3 or 4 adverse events was very low, with no statistically significant differences between groups in severe adverse events related to ALT, AST, total bilirubin, cholesterol, or triglycerides. There were statistically significant, but not clinically meaningful, differences between infant groups in ALT and creatinine. The proportion of infants with Grade 3 or 4 adverse events was very low, and there were no statistically significant differences in severe adverse events related to ALT, AST, BUN, or creatinine. CONCLUSION: The proportions of women and infants with severe laboratory adverse events were very low. Increased LPV/r dosing during the third trimester of pregnancy appears to be safe for HIV-infected women and their infants.

Prevalence and factors associated with darunavir resistance mutations in multi-experienced HIV-1-infected patients failing other protease inhibitors in a referral teaching center in Brazil

Information about resistance profile of darunavir (DRV) is scarce in Brazil. Our objectives were to estimate the prevalence of DRV resistance mutations in patients failing protease inhibitors (PI) and to identify factors associated with having more DRV resistance mutations. All HIV-infected patients failing PI-based regimens with genotyping performed between 2007 and 2008 in a referral teaching center in São Paulo, Brazil, were included. DRV-specific resistance mutations listed by December 2008 IAS-USA panel update were considered. Two Poisson regression models were constructed to assess factors related to the presence of more DRV resistance mutations. A total of 171 HIV-infected patients with available genotyping were included. The number of patients with lopinavir, saquinavir, and amprenavir used in previous regimen were 130 (76 percent), 83 (49 percent), and 35 (20 percent), respectively. The prevalence of major DRV resistance mutations was 50V: 5 percent; 54M: 1 percent; 76V: 4 percent; 84V: 15 percent. For minor mutations, the rates were 11I: 3 percent; 32I: 7 percent; 33F: 23 percent; 47V: 6 percent; 54L: 6 percent; 74P: 3 percent; 89V: 6 percent. Only 11 (6 percent) of the genotypes had > 3 DRV resistance mutations. In the clinical model, time of HIV infection of > 10 years and use of amprenavir were independently associated with having more DRV resistance mutations. In the genotyping-based model, only total number of PI resistance mutations was associated with our outcome. In conclusion, the prevalence of DRV mutations was low. Time of HIV infection, use of amprenavir and total number of PI resistance mutations were associated with having more DRV mutations.

Nutritional Status and the Use of Protease Inhibitors Among Hiv-infected Children in Klang Valley, Malaysia

This study determined the association between nutritional status and the use of protease inhibitors (PI) containing regimen among HIV-infected children receiving treatment at the referral centres in Klang Valley. A total of 95 children currently on antiretroviral (ARV) therapy, aged one to eighteen years, were recruited using purposive sampling. Demographic data, anthropometric measurements, medical history, were collected using a structured questionnaire. Serum micronutrients levels and lipid profile were also examined using blood samples. Mean age was 8.8 3.9 years and 44.2% were on PI. Age ( 2 = 10.351, p = .006), weight-for-age ( 2 = 6.567, p = .010), serum selenium ( 2 = 4.225, p = .040) and HDL-C ( 2 = 7.539, p = .006) were significantly associated with the use of PI. Fewer children on PI were deficient in selenium as compared to those not on PI. On the contrary, more children on PI were underweight and had low HDL-C. The use of PI was found to have both positive and negative effects with better selenium level but poorer HDL-C level and weight status.

Study of genotypic resistance mutations of protease and reverse transcriptase in non-therapeutic acquired immune deficiency syndrome patients in Heiiongjiang Province / 中华传染病杂志

Objective To study the presence of drug resistant mutations of protease and reverse transcriptase among human immunodeficiency virus (HIV)-1 strains isolated from treatment naive HIV/ acquired immune deficiency syndrome (AIDS) patients in Heilongjiang Province of China and to provide the baseline data for starting antiretroviral therapy in this area. Methods The protease and reverse transcriptase gene sequences were amplified by nested-polymerase chain reaction (PCR) and then sequenced. The results were compared to the subtype B consensus amino acid sequence and analyzed with Stanford HIV-db drug resistance sequence interpretation. Results The results showed that HIV strains from 49 patients were classified as subtype B'. No primary mutations associated with protease inhibitor were detected. Some secondary mutations associated with protease inhibitor were detected, which included V77I(91.5%), L63P(76.6%), I93L(74.5%), E35D(61.7%), R57K (19.1%), R41K(10.6%), A71V(8.5%), M36I(8.5%), L10I(6.4%), D60E(6.4%), L89M (4.2%) and G16E(2. 1%). Only one case had a primary mutation M184I that was associated with resistance to reverse transcriptase inhibitors. However, many secondary mutations associated with resistance to reverse transcriptase inhibitors were found, including I135L/T/R/V(81.8%), V106I(22.7%), V179D/E(11.4%), R211K(9.1%), L214F(4.5%), V189I(4.5%) and V108I(2. 3%).Conclusions The prevalence of genotypic anti-HIV drug resistance is very low in treatment naive HIV/AIDS patients in Heilongjiang Province. However, closely monitoring on drug resistance mutation is very important for preventing the development and prevalence of multi-drug resistant or cross drug resistant HIV.

HIV-1 protease inhibitor nelfinavir decreases insulin secretion from rat insulinoma INS-1 cells / 中华内分泌代谢杂志

Rat INS-1 cells treated with HIV-1 protease inhibitor Nelfinavir for 48 h showed that both basal and glucose-stimulated insulin secretion decreased, the latter was more marked, suggesting that long-term treatment with Nelfinavir may impair ?-cell function.