Characterization of HIV risks in a Brazilian sickle cell disease population.

BACKGROUND: A low prevalence of HIV in sickle cell disease (SCD) patients has been reported in the literature though mechanisms for this are not understood. METHODS: HIV risk behaviors were compared between SCD cases and non-SCD controls using a self-administered audio computer-assisted self-interview. SCD cases were recruited from a multi-center SCD cohort established in Brazil; controls were recruited from SCD social contacts. Categorical variables were analyzed using Chi-Square or Fisher exact test. Continuous variables were compared using the Mann-Whitney U test. RESULTS: There were 152 SCD cases and 154 age/location matched controls enrolled at three participating Brazilian centers during 2016-17. No significant differences in number of sexual partners (lifetime or previous 12 months), male-to-male sex partners or intravenous drug use were observed. Cases received more transfusions, surgeries, and acupuncture treatment. CONCLUSIONS: Besides the risk of transfusion-transmitted HIV, which is now exceedingly rare, SCD and non-SCD participants demonstrated similar HIV risk behaviors. Causes other than risk behaviors such as factors inherent to SCD pathophysiology may explain the reported low prevalence of HIV in SCD.

Delayed-type hypersensitivity in classic Kaposi sarcoma patients and controls.

BACKGROUND: Immune perturbation likely affects the development of Kaposi sarcoma (KS) among people infected with the KS-associated herpesvirus (KSHV). We tested whether KSHV-seropositive individuals or cases of classic KS (cKS), which typically originates in the leg, had differing delayed-type hypersensitivity (DTH) in the forearm or leg. METHODS: Mantoux DTH with three antigens (Candida, tetanus, PPD) was performed on the forearm and leg of 15 cKS cases, 14 KSHV-positives without KS, and 15 KSHV-negative controls. The diameters of induration responses were compared by group and body site. RESULTS: Leg DTH was greater than forearm DTH among controls (mean difference 5.6 mm, P=0.0004), whereas this was not observed in cKS cases (-2.2 mm, P=0.32) or KSHV-positives (0.5 mm, P=0.56). Leg-minus-forearm DTH difference was greater in controls compared with cKS cases (P=0.004) and KSHV-positives (P=0.002). Leg-plus-forearm DTH was similar in controls (mean 28.2 mm) and cKS cases (24.5 mm, P=0.60), but it was reduced in KSHV-positives (11.8 mm, P=0.02), particularly in the leg (P=0.004) and marginally in the forearm (P=0.07). CONCLUSION: KS cases had weaker DTH only in the leg, whereas both body sites appeared weaker in KSHV-positives without KS. Both systemic and regional immune alterations may influence the development of this malignancy.

Correlates of high hepatitis C virus RNA load in a cohort of HIV-negative and HIV-positive individuals with haemophilia.

Hepatitis C virus (HCV) treatment failure and disease progression are more likely with high HCV-RNA load. Correlates of high HCV-RNA load in individuals with haemophilia are largely unknown. Among 1266 interferon naïve HCV-infected individuals with haemophilia, we compared those with high (> 2 x 106 HCV-RNA copies/mL) to lower viral load, overall and stratifying on HIV co-infection status using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Overall, high HCV load was independently associated with longer duration of HCV infection (P(trend)=0.0001), body mass index ≥ 25 kg/m² (OR=1.4, 95% CI=1.1-1.9), and HIV co-infection (OR=1.4, 95% CI=1.0-1.8). Among 795 HIV-negative participants, high HCV-RNA load was associated with older age at HCV acquisition (OR=1.9 for > 15 years vs ≤ 2 years, P(trend)=0.008), and lower AST/platelet ratio (P(trend)=0.01), in addition to longer duration of HCV infection (P(trend)=0.0008), and body mass index ≥ 25 kg/m² (OR=1.6, P=0.005). Among 471 HIV-positive individuals, anti-retroviral therapy (ART) was the only variable associated with high HCV-RNA load (OR=1.8, CI=1.1-2.9 for combination ART; OR=1.8, CI=0.9-3.4, for other ART vs no treatment). High HCV-RNA load with haemophilia is more likely with longer duration of infection, older age at infection, higher body mass index, and antiretroviral therapy. These findings may help identify individuals at increased risk of HCV treatment failure and progression to end-stage liver disease.

Treatment of classic Kaposi sarcoma with a nicotine dermal patch: a phase II clinical trial.

BACKGROUND: Kaposi sarcoma (KS), a malignancy of dermal endothelial cells that is caused by human herpesvirus 8 (HHV8) infection, is sensitive to perturbations of immunity. Nicotine might be effective against KS because of its immunologic and vascular effects and because smoking is associated with a low risk of KS. OBJECTIVE AND STUDY DESIGN: We conducted a masked, randomized phase 2 clinical trial of transdermal nicotine and placebo patches to assess the safety and efficacy of nicotine against classic KS (cKS). SUBJECTS AND METHODS: Three cKS lesions, predominantly nodules, in each of 24 non-smoking patients were randomly assigned to 15 weeks continuous treatment with nicotine patch (escalated to 7 mg), identical masked placebo patch or no patch. Changes in lesion area and elevation from baseline through six follow-up visits, by direct measurement and by two independent readers using digital photographs of the lesions, were compared using non-parametric and regression methods. Changes in longitudinal levels of HHV8 antibodies and DNA in blood cells were similarly assessed. RESULTS: There were no systemic or serious adverse events, and compliance was good. One patient resumed smoking and discontinued patches, and two patients withdrew at week 12 for unrelated indications. Six (29%) of the remaining 21 suspended use of patches to relieve local skin irritation; four of these six completed the trial at reduced dose. Treatment assignment was not associated with significant or consistent changes in cKS lesion area or elevation, HHV8 viral load or antibodies. CONCLUSION: Transdermal nicotine and placebo patches caused no serious toxicities but had no demonstrable effect on nodular cKS lesions or HHV8 levels.

Cholesterol and coronary heart disease: predicting risks in men by changes in levels and ratios.

BACKGROUND: Little is known about the relative ability of different measures of change in cholesterol to discriminate coronary heart disease risk. We evaluated this ability for changes in low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, LDL/HDL ratios, and total cholesterol/HDL ratios. METHODS: We predicted risks of coronary heart disease using data from 3641 men in the Lipid Research Clinics Coronary Primary Prevention Trial. Treating these patients as a cohort, we estimated risks associated with changes in cholesterol levels independent of the patients' randomization group. RESULTS: Changes in LDL and HDL cholesterol when used in combination were each significant predictors of coronary heart disease risk (odds ratios [OR] for 10% increases, 1.15 and 0.84, respectively; P < 0.001). Changes in LDL/HDL and total cholesterol/HDL ratios had similar discriminating ability (OR for 10% increases, 1.17 and 1.21, respectively; P < 0.0001). In the best discriminating models, changes in ratios added information about risks to changes in LDL cholesterol, although changes in LDL cholesterol levels failed to add information to changes in ratios. CONCLUSIONS: Changes in total cholesterol/HDL and LDL/HDL ratios were better predictors of risk for coronary heart disease than were changes in LDL cholesterol levels alone. When assessed as percentage changes averaged during the first two months of intervention, they were among the best discriminators of risk. Clinicians selecting treatments for intervention should include among their considerations the treatment's effect on both LDL and HDL cholesterol rather than their effects on LDL cholesterol levels alone.

Detection of human immunodeficiency virus and other retroviruses in cell culture supernatants by a reverse transcriptase microassay.

A micromethod for the detection of human immunodeficiency virus (HIV) and other retroviruses in cell culture supernatants is described which applies a DEAE ion exchanger for recovery of polynucleotides synthesized in vitro by the retroviral reverse transcriptase. Cell culture, sample preparation, and test performance including the washing step are adapted to microtitre plates. Compared to the standard method this technique produced less non-specific reactions, resulting in a more than 3-fold higher sensitivity, a higher reproducibility due to lower intrarun variations and allowed an increase in the daily sample accomplishment per person 3- to 4-fold at lower costs per sample.