Background. Variables influencing serum hepatitis C virus (HCV) RNA levels and genotype distribution in individuals with human immunodeficiency virus

Combination antiretroviral therapy (cART) reduces morbidity and mortality in human immunodeficiency virus (HIV) infection, but it may also alter the clinical course of subclinical opportunistic infections and can even induce autoimmune disease. These atypical presentations are known as immune restoration disease (IRD), immune reconstitution syndrome/immune recovery syndrome (IRS), or immune restoration inflammatory syndrome (IRIS). We report the case of a 27-year-old, HIV-1–positive woman who developed hyperthyroidism attributable to Graves' disease (GD) after commencing potent cART. At the initiation of cART, her CD4 T cell count was 15 cells/µL and plasma HIV RNA 35 000 copies/mL. Her commencement of cART resulted in complete viral suppression and subsequent improvement of the CD4 T-cell count. Three years later, the diagnosis of GD was established based on a typical clinical picture and the results of hormonal and immunological analyses. It coincided with a 58-fold rise of the CD4 T cells. Retrospective analysis of serum samples revealed normal thyroid function and lack of anti-thyroid peroxidase (anti-TPO), anti– thyroid-stimulating hormone receptor (anti-TSHR), and anti-thyroglobulin (anti-TG) autoantibodies at the beginning of cART. HLA class II gene examination did not reveal susceptibility for the GD development in this patient. We suggest that GD in our patient was an IRD, and advise this as a possible differential diagnosis in patients presenting with hyperthyroidism on cART. To provide further details relevant to this case, we also review the literature concerning IRD-GD.

Abstract: Given the decline in mortality among HIV-infected patients, it has become increasingly important to consider delayed disease-related and/or anti-HIV therapy-related adverse effects, such as lipodystrophy, when choosing initial therapy. Data from the MONARK trial allowed for comparison of the potential lipodystrophic effects of lopinavir/ritonavir (LPV/r) monotherapy with those of triple therapy with LPV/r plus zidovudine (ZDV) and lamivudine (3TC). This was a randomized, open-label, multinational study that included 136 antiretroviral-naive HIV-infected patients. A portion of study patients underwent evaluations of limb and trunk fat tissue by dual-energy x-ray absorptiometry at baseline and after 48 weeks of treatment (and 96 weeks in some patients). Sixty-three patients had paired absorptiometry data at baseline and week 48 (13 patients at week 96). At week 48, median change in limb fat was - 63 g on LPV/r monotherapy versus -703 g on LPV/r + ZDV/3TC triple therapy (p=0.014). The proportion of patients with fat loss ( > 20% loss in limb fat) was significantly lower with LPV/r monotherapy (4.9% versus 27.3%; p=0.018). Changes in trunk fat did not differ significantly between treatments. Nonetheless, limb fat and trunk fat varied in the same direction with both treatments. The decrease in arm lean mass was also significantly less in patients receiving LPV/r monotherapy. Only treatment type emerged as a significant predictor of fat loss (odds ratio, 7.06; 95% CI, 1.11-78.69). These results suggest that LPV/r, and possibly other protease inhibitors, may not be the main contributor to lipoatrophy in HIV-infected patients receiving triple therapy.

HIV infected patients, especially those treated with antiretroviral (ARV) drugs, show an increased risk and incidence of cardiovascular disease. The aim of this study was to evaluate the progression of subclinical atherosclerosis in the carotid arteries, expressed as the value of carotid intima-media thickness (cIMT) and the amount of atherosclerotic plaques, and to analyze the correlation between cIMT and risk factors for cardiovascular diseases in a cohort of HIV infected patients. The analysis included 72 HIV infected patients, mean age 39.4 years, and 27 healthy HIV negative individuals, matched for age and sex. The data collected included evaluation of the infection, ARV treatment, past cardiovascular events, assessment of traditional and nontraditional risk factors for cardiovascular diseases, cIMT measurements and amount of atherosclerotic plaques in the carotid arteries. HIV infected patients show more advanced subclinical atherosclerosis in the carotid arteries (cIMT and plaques incidence). The cardiovascular risk profile of the HIV infected patients is significantly different from HIV negative people. Among the HIV positive group lower body mass index (BMI) and higher waist/hip ratio (WHR) are observed. The concentration of all cholesterol fractions is lower, whereas the concentration of triglycerides is higher. Cigarette smoking is more common among HIV-infected individuals. A strong statistical correlation between cIMT and age, hypertension, non-high-density lipoprotein (non-HDL) cholesterol and ARV time were found. Total and LDL cholesterol, and lifetime smoking exposure also affect the cIMT. The relationship between cIMT and current HIV RNA may indicate the impact of the current infection status on the cIMT dynamics in this subpopulation.

Estimating the prevalence of accumulated HIV drug resistance in patients receiving antiretroviral therapy (ART) is difficult due to lack of resistance testing at all occasions of virological failure and in patients with undetectable viral load. A method to estimate this for 6498 EuroSIDA patients who were under follow-up on ART at 1 July 2008 was therefore developed by imputing data on patients with no prior resistance test results, based on the probability of detecting resistance in tested patients with similar profiles. Using all resistance test results available, predicted intermediate/high-level resistance to specific drug classes [nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)] was derived using the Stanford algorithm v5.1.2. Logistic regression models were then employed to estimate predicted probability of resistance to each drug class for given values of current viral load, history of virological failure and previous virological suppression. Based on these predicted probabilities and patients’ covariate profiles, estimates of prevalence in 5355 patients with no prior test results were obtained. Overall prevalence of resistance was estimated by pooling these data with those observed in the remaining 1143 tested patients. Prevalence of NRTI, NNRTI and PI resistance was estimated as 43% (95% confidence interval: 39%–46%), 15% (13%–18%) and 25% (22%–28%), respectively. This method provides estimates for the proportion of treated patients in a cohort who harbour resistance on a given date, which are less likely to be affected by selection bias due to missing resistance data and will allow us to estimate prevalence of resistance to different drug classes at specific timepoints in HIV-infected populations on ART.