Cumulative exposure to TDF and, among protease inhibitors, LPV/RTV was independently predictive of increased risk of osteoporotic fracture in the HAART era.

Genotyping for UGT1A1*28 before initiation of ART would identify HIV-infected individuals at risk for hyperbilirubinemia and decrease episodes of jaundice.

We observed no association between cumulative or current abacavir use and AMI or CVA. Abacavir use was more common than was tenofovir use among patients with prior chronic kidney disease, and chronic kidney disease independently predicted higher rates of AMI and CVA.

BackgroundAmong HIV-infected patients, hepatitis C virus (HCV) coinfection is associated with lower cholesterol levels, but it remains unclear how it affects cardiovascular outcomes. MethodsWe performed logistic regression to evaluate acute myocardial infarction (AMI) and cerebrovascular disease (CVD) events by HCV status among HIV-infected US veterans in the highly active antiretroviral therapy (HAART) era (1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004). We then performed survival analyses to evaluate incident AMI and CVD, exploring antiretroviral therapy (ART) as a time-dependent variable. ResultsA total of 19 424 HIV-infected patients [31.6% of whom were HCV-coinfected (HIV/HCV)] contributed 76 376 patient-years of follow-up. HCV coinfection was associated with lower rates of hypercholesterolaemia (18.0% in HIV/HCV vs. 30.7% in HIV-only patients; Po0.001), but higher rates of hypertension (43.8% vs. 35.6%; Po0.0001), type 2 diabetes mellitus (16.2% vs. 11.1%; Po0.0001) and smoking (36.7% vs. 24.7%; P 5 0.009). Rates of AMI and CVD were significantly higher among HIV/HCV than HIV-only patients: 4.19 vs. 3.36 events/1000 patient-years, respectively (Po0.001), for AMI; and 12.47 vs. 11.12 events/1000 patient-years, respectively (Po0.001), for CVD. When analyses were controlled for diabetes mellitus, hypertension, age and duration of ART, hazard ratios (HRs) among those with HIV/HCV (vs. HIV only) were 1.25 [95% confidence interval (CI) 0.98-1.61; P 5 0.072] for AMI and 1.20 (CI 1.04-1.38; P 5 0.013) for CVD. Hypertension (HR 2.05; Po0.001), greater age (HR 1.79; Po0.001) and longer duration (cumulative years) of antiretroviral use (HR 1.12; P 5 0.0411) were also associated with increased risk of AMI in the adjusted model. ConclusionsIn the HAART era, HCV coinfection was associated with a significantly increased risk of CVD and a trend towards an increased risk of AMI among HIV-infected patients.Keywords: acute myocardial infarction, cerebrovascular disease, hepatitis C, highly active antiretroviral therapy, incidence IntroductionThe increase in overall survival of HIV-infected patients has been associated with a shift in underlying cause of death, with decreased representation of AIDS-related causes and increased representation of non-AIDS-related deaths, which rose by 33% in one recent series [1]. The most prevalent non-AIDS-related causes of morbidity and mortality are chronic liver disease, metabolic complications including cardiovascular disease, and non-AIDSdefining malignancies [1][2][3].It has been estimated that 15 to 30% of all HIV-infected persons are also infected with the hepatitis C virus (HCV) [4,5]. The percentage of HIV-infected patients coinfected with HCV was found to vary significantly in previous studies depending on risk factors, from as low as 4% among HIV-infected non-drug users to as high as 89% among HIV-infected injecting drug users (IDUs) [4][5][6][7]. It is now well established that there is a significantly elevated risk of severe liver disease in persons who are coinfected D...

BackgroundEarly detection of several skin-related neglected tropical diseases (skin NTDs)–including leprosy, Buruli ulcer, yaws, and scabies- may be achieved through school surveys, but such an approach has seldom been tested systematically on a large scale in endemic countries. Additionally, a better understanding of the spectrum of skin diseases and the at-risk populations to be encountered during such surveys is necessary to facilitate the process.MethodsWe performed a school skin survey for selected NTDs and the spectrum of skin diseases, among primary schoolchildren aged 5 to 15 in Côte d’Ivoire, West Africa. This 2-phase survey took place in 49 schools from 16 villages in the Adzopé health district from November 2015 to January 2016. The first phase involved a rapid visual examination of the skin by local community healthcare workers (village nurses) to identify any skin abnormality. In a second phase, a specialized medical team including dermatologists performed a total skin examination of all screened students with any skin lesion and provided treatment where necessary.ResultsOf a total of 13,019 children, 3,504 screened positive for skin lesions and were listed for the next stage examination. The medical team examined 1,138 of these children. The overall prevalence of skin diseases was 25.6% (95% CI: 24.3–26.9%). The predominant diagnoses were fungal infections (n = 858, prevalence: 22.3%), followed by inflammatory skin diseases (n = 265, prevalence: 6.9%). Skin diseases were more common in boys and in children living along the main road with heavy traffic. One case of multi-bacillary type leprosy was detected early, along with 36 cases of scabies. Our survey was met with very good community acceptance.ConclusionWe carried out the first large-scale integrated, two-phase pediatric multi-skin NTD survey in rural Côte d’Ivoire, effectively reaching a large population. We found a high prevalence of skin diseases in children, but only limited number of skin NTDs. With the lessons learned, we plan to expand the project to a wider area to further explore its potential to better integrate skin NTD screening in the public health agenda.

APOBEC3F and APOBEC3G (hA3F and hA3G) are part of an innate mechanism of antiretroviral defense. The human immunodeficiency virus type 1 (HIV-1) accessory protein Vif targets both proteins for proteasomal degradation. Using mRNA from peripheral blood mononuclear cells of 92 HIV-infected subjects not taking antiretroviral therapy and 19 HIV-uninfected controls, we found that hA3F (P < 0.001) and hA3G (P ‫؍‬ 0.016) mRNA levels were lower in HIV-infected subjects and were positively correlated with one another (P ‫؍‬ 0.003). However, we found no correlation in the abundance of either hA3F or hA3G mRNA with either viral load or CD4 counts in HIV-infected subjects.

One approach to target the long-term metabolic toxicity and disfiguring body-shape changes associated with antiretroviral therapy is to switch one component of a regimen to an alternative drug, usually from a different class of antiretrovirals. Most commonly, substitutions have involved protease inhibitors, but the thymidine analogue nucleosides, especially stavudine, have been investigated more recently. Certain trends from these studies have emerged. First, if the patient has had sustained viral suppression, switching therapy is generally virologically safe. Second, metabolic disturbances, such as insulin resistance and dyslipidemia, appear to be at least partially reversible. Substitution of other agents for protease inhibitors has not been associated with reversal or improvement in fat redistribution. Studies in which thymidine analogue reverse-transcriptase inhibitors have been switched have reported modest improvements in peripheral lipoatrophy. Larger, controlled, long-term studies and a more standardized approach to definition of metabolic and morphological abnormalities are needed.

BackgroundNRTI-sparing regimens may avoid long-term mitochondrial, bone and renal toxicities and maintain viral suppression.MethodsIn the RADAR study, 85 antiretroviral-naïve HIV-infected patients were randomized to receive either raltegravir (RAL) (n = 42) or tenofovir/emtricitabine (TDF/FTC) (n = 43), each with ritonavir-boosted darunavir (DRV/r). Virologic efficacy was assessed at weeks 24 and 48. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA) scan at baseline and week 48, and bone turnover markers (BTM) assessed at weeks 0, 16 and 48.ResultsUsing an intention-to-treat analysis, 62.5% of RAL subjects and 83.7% of TDF/FTC subjects were responders (VL<48 copies/mL) at week 48 (p = 0.045; chi-square test). The proportions of patients achieving VL<200 copies/mL were similar: 72.5% and 86.0% (p = 0.175). Premature treatment discontinuation was the main cause for failure. No treatment-emergent resistance was observed. Changes from baseline in RAL vs. TDF/FTC for CD4+ (+199 vs. +216 cells/µL, p = 0.63), total cholesterol/HDL (−0.25 vs. −0.71 mg/dL (p = 0.270), and eGFR (−4.4 vs. −7.9 ml/min, p = 0.44) were comparable between groups. Changes in subtotal BMD to week 48 were: +9.2 with RAL vs. −7 g/cm2 with TDF/FTC (p = 0.002). Mean CTX changes were +0.04 vs. +0.24 ng/mL (p = 0.001), and mean P1NP changes were +3.59 vs. +30.09 ng/mL (p = 0.023). BTM changes at week 16 predicted change in BMD by week 48 (R = −0.394, p = 0.003 for CTX; and R = −0.477, p<0.001 for P1NP).ConclusionThe NRTI-sparing regimen RAL+DRV/r did not achieve similar week 48 virologic efficacy compared with TDF/FTC+DRV/r, but was better with regard to markers of bone health.Trial RegistrationClinicalTrials.gov NCT 00677300