Recommendations for evaluation and management of bone disease in HIV

Thirty-four human immunodeficiency virus (HIV) specialists from 16 countries contributed to this project, whose primary aim was to provide guidance on the screening, diagnosis, and monitoring of bone disease in HIV-infected patients. Four clinically important questions in bone disease management were identified, and recommendations, based on literature review and expert opinion, were agreed upon. Risk of fragility fracture should be assessed primarily using the Fracture Risk Assessment Tool (FRAX), without dual-energy X-ray absorptiometry (DXA), in all HIV-infected men aged 40-49 years and HIV-infected premenopausal women aged ≥40 years. DXA should be performed in men aged ≥50 years, postmenopausal women, patients with a history of fragility fracture, patients receiving chronic glucocorticoid treatment, and patients at high risk of falls. In resource-limited settings, FRAX without bone mineral density can be substituted for DXA. Guidelines for antiretroviral therapy should be followed; adjustment should avoid tenofovir disoproxil fumarate or boosted protease inhibitors in at-risk patients. Dietary and lifestyle management strategies for high-risk patients should be employed and antiosteoporosis treatment initiated

Analysis of HIV-1 drug resistant mutations by line probe assay and direct sequencing in a cohort of therapy naive HIV-1 infected Italian patients

BACKGROUND: The routine determination of drug resistance in newly HIV-1 infected individuals documents a potential increase in the transmission of drug-resistant variants. Plasma samples from twenty seven therapy naive HIV-1 infected Italian patients were analyzed by the line probe assay (LIPA) and the TruGene HIV-1 assay for the detection of mutations conferring resistance to HIV-1. RESULTS: Both tests disclosed amino-acid substitutions associated with resistance in a variable number of patients. In particular, two mutations (K70R and V118I), detectable by LIPA and by sequencing analysis respectively, revealed resistance to NRTIs in two plasma samples. At least three mutations conferring resistance to NNRTIs, not detectable by commercial LIPA, able to reveal mutations associated only with nucleoside reverse transcriptase analogues, were disclosed by viral sequence analysis. Moreover, most samples showed mutations correlated with resistance to protease inhibitors. Remarkably, a key mutation, like V82A (found as a mixture), and some "indeterminate" results (9 samples), due the absence of signal on the lines corresponding to a specific probe, was revealed only by LIPA, while a variable number of secondary mutations was detectable only by TruGene HIV-1 assay. CONCLUSION: Even if further studies are necessary to establish the impact of different tests on the evaluation of drug-resistant strains transmission, LIPA might be useful in a wide population analysis, where bulk results are needed in a short time, while sequencing analysis, able to detect mutations conferring resistance to both NRTIs and NNRTIs, might be considered a more complete assay, albeit more expensive and more technically complex

First-line HIV treatment: evaluation of backbone choice and its budget impact

OBJECTIVE: The gradual increase of persons living with HIV, mainly due to the reduced mortality achieved with effective antiretroviral therapies, calls for increased rationality and awareness in health resources consumption also during the early illness phases. Aim of this work is the estimation of the budget impact related to the variation in backbone prescribing trends in naïve patients.METHODS: Target population is the number of patients starting antiretroviral therapy each year, according to the Italian HIV surveillance registry, excluding patients receiving non-authorized or non-recommended regimens. We modeled 3-year mortality and durability rates on a dynamic cohort, basing on international literature. A prevalent patients analysis has also been conducted, for which the model is fed by a closed cohort consisting of all the patients without experience of virologic failure. The aim of this collateral analysis is to estimate the difference in current annual expenditures if the past prescription trends for patients starting therapy would have led to the evaluated hypothetical scenarios. Current Italian market shares of triple regimens containing first-choice or alternative backbones (tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine) are compared to three hypothetical scenarios (base-case, minimum and maximum) in which increasing shares of patients eligible to abacavir/lamivudine start first line treatment with this backbone. Annual cost for each regimen comprises drugs acquisition under hospital pricing rules, monitoring exams and preventive tests, valued basing on regional reimbursement tariffs.RESULTS: According to current prescribing trends, in the next three years about 13,000 patients starting HIV therapy will receive tenofovir/emtricitabine (83% of the target population), and minor portions other regimens (9% abacavir/lamivudine, 8% zidovudine/lamivudine). Patients that would be eligible to abacavir/lamivudine are 1.5, 4.5 and 6 thousand more than those presently treated according to the three hypothetical scenarios, leading to a cumulative saving of 850 thousand, 2.4 million and 3.3 million euro, respectively. If in the past the same modification of first line prescription trend was adopted, the annual current cost saving would vary from 922 thousands to 7.3 million euro. Most of this amount is due to reduced acquisition costs and, secondarily, to lower monitoring needs.CONCLUSION: Where patient features don't force the choice of the backbone, abacavir/lamivudine prescription may induce substantial savings, allowing the release of resources needed to manage more complicated/advanced cases

PrEP in Italy: The time may be ripe but who’s paying the bill? A nationwide survey on physicians’ attitudes towards using antiretrovirals to prevent HIV infection

Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians’ knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP’s financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practic

HIV-1 and recombinant gp120 affect the survival and differentiation of human vessel wall-derived mesenchymal stem cells

BAckground:HIV infection elicits the onset of a progressive immunodeficiency and also damages several other organs and tissues such as the CNS, kidney, heart, blood vessels, adipose tissue and bone. In particular, HIV infection has been related to an increased incidence of cardiovascular diseases and derangement in the structure of blood vessels in the absence of classical risk factors. The recent characterization of multipotent mesenchymal cells in the vascular wall, involved in regulating cellular homeostasis, suggests that these cells may be considered a target of HIV pathogenesis. This paper investigated the interaction between HIV-1 and vascular wall resident human mesenchymal stem cells (MSCs). RESULTS: MSCs were challenged with classical R5 and X4 HIV-1 laboratory strains demonstrating that these strains are able to enter and integrate their retro-transcribed proviral DNA in the host cell genome. Subsequent experiments indicated that HIV-1 strains and recombinant gp120 elicited a reliable increase in apoptosis in sub-confluent MSCs. Since vascular wall MSCs are multipotent cells that may be differentiated towards several cell lineages, we challenged HIV-1 strains and gp120 on MSCs differentiated to adipogenesis and endotheliogenesis. Our experiments showed that the adipogenesis is increased especially by upregulated PPAR\u3b3 activity whereas the endothelial differentiation induced by VEGF treatment was impaired with a downregulation of endothelial markers such as vWF, Flt-1 and KDR expression. These viral effects in MSC survival and adipogenic or endothelial differentiation were tackled by CD4 blockade suggesting an important role of CD4/gp120 interaction in this context. CONCLUSIONS: The HIV-related derangement of MSC survival and differentiation may suggest a direct role of HIV infection and gp120 in impaired vessel homeostasis and in genesis of vessel damage observed in HIV-infected patients

Non-AIDS defining cancers in the D:A:D Study - time trends and predictors of survival : A cohort study

Background: Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.Methods: Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.Results: Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.Conclusions: The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC. © 2013 Worm et al.; licensee BioMed Central Ltd