Efficacy and safety of switching to dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (TDF) or elvitegravir/cobicistat/emtricitabine/TDF in virologically suppressed HIV-infected patients in clinical practice: results from a multicentre, observational study.

OBJECTIVES: The aim of the study was to compare the efficacy and tolerability of switching antiretroviral therapy to dolutegravir + emtricitabine/tenofovir disoproxil fumarate (TDF) with those of switching to elvitegravir/cobicistat/emtricitabine/TDF in clinical practice. METHODS: In a multicentre real-life observational study, we analysed data for HIV-infected patients on antiretroviral treatment with viral load < 50 HIV-1 RNA copies/mL switching to dolutegravir + emtricitabine/TDF (dolutegravir group) or elvitegravir/cobicistat/emtricitabine/TDF (elvitegravir group). Follow-up was censored at 48 weeks. RESULTS: The 48-week estimated proportion maintaining virological efficacy was 96.1% with dolutegravir (n = 123) and 95.4% with elvitegravir (n = 186; P = 0.941). Patients in the dolutegravir group showed more treatment discontinuations, but these were mainly as a result of simplification. The elvitegravir group showed more discontinuations because of renal adverse events (2.7% versus 0% with dolutegravir). Interestingly, no difference was observed between the two regimens in central nervous system toxicity-related discontinuations. Switching to dolutegravir was associated with a better blood lipid profile. CONCLUSIONS: Switching to dolutegravir + emtricitabine/TDF was associated with similar efficacy and tolerability to switching to elvitegravir/cobicistat/emtricitabine/TDF in virologically suppressed patients in clinical practice, although reasons for discontinuation showed differences between regimens. These results should be interpreted with caution, as this is a nonrandomized comparison.

The additional role of 18F-FDG PET/CT in prosthetic valve endocarditis.

OBJECTIVE: The purpose of the present review is an update on the diagnosis of prosthetic valve endocarditis (PVE), evaluating the additional value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to the standard modified DUKE criteria on which for a long time is based the diagnostic strategy of the disease. MATERIALS AND METHODS: We did a comprehensive research on the studies reported in the literature and regarding the employment of 18F-FDG PET/CT in the early diagnosis of PVE in patients with suspected disease. Scientific databases have been examined such as Medline and PubMed, followed by a review of citations and reference lists. The research included the following terms: infective endocarditis, prosthetic heart valve and cardiac valve replacement infections, 18F-FDG PET/CT and endocarditis. RESULTS: The recent studies reported in the literature on the PVE diagnostic approaches showed elevated sensitivity and specificity values of 18F-FDG PET/CT ranging from 73 to 96.6% and from 80 to 94%, respectively, reducing the number of misdiagnosed patients. The usefulness of the radioisotopic procedure is even more important when the other diagnostic conventional diagnostic tools, such as echocardiography, are inconclusive or negative in patients in whom the diagnosis of PVE is definitively ascertained. However, false negative and positive results of 18F-FDG PET/CT were also ascertained in some studies interfering with image interpretation even if such limitation can be reduced with an adequate patient preparation, with a better knowledge of clinical course of the disease, of the treatment in progress and of the different technical aspects of the method. CONCLUSIONS: In different studies reported in the literature, 18F-FDG PET/CT proved to improve the diagnostic accuracy of the conventional modified DUKE criteria in patients with suspected IE, and in particular with PVE, giving the highest diagnostic performance and providing additional diagnostic benefits. Thus, the radioisotopic hybrid procedure should be included in the diagnostic protocol of PVE as complementary tool to modified DUKE criteria. Finally, the usefulness of 18F-FDG PET/CT in monitoring the response to antibiotic therapy, although the few data reported in the literature are encouraging, needs more numerous studies and with a major number of cases.

Body fat changes in HIV patients on highly active antiretroviral therapy (HAART): a longitudinal DEXA study.

OBJECTIVE: We aimed to quantitatively evaluate body fat composition in a group of HIV patients treated with Highly Active Anti-retroviral Therapy (HAART) to ascertain both fat loss and fat distribution changes and to identify possible therapeutic and host related associated risk factors. PATIENTS AND METHODS: A total of 180 patients with available total body DEXA scan were assigned to a) Group 1, with clinically evident body fat changes, (BFC) and b) Group 2, without BFC. Clinical and immunovirologic data were collected. We used Student t-test and x2 or Fisher exact test to compare the characteristics of the two groups. Paired t-test was used to compare basal and follow-up data. The relationships between variables were evaluated by calculating Pearson's correlation coefficient and its significance. RESULTS: HAART duration was significantly (p<0.0001) higher for patients in Group 1 than in Group 2, as well as PI (p<0.02) and NRTI (p<0.002) therapy duration. Current CD4 count and CD4 rise from nadir resulted significantly higher in Group 1 than in Group 2 (p<0.02 and 0.006, respectively). Whole Body Fat (WBF), Peripheral Fat (PF) and Leg (L) fat negatively correlated with PI and NRTI therapy duration, while Trunk Fat (TF)/PF positively correlated with PI and NNRTI duration. No significant correlation was found, instead, with NNRTI therapy duration. At 5-year follow-up, we registered a further increase in TF, Arms (A) and L fat, especially in PI-treated patients. CONCLUSIONS: Body fat changes should always be considered when dealing with HIV-affected patients on HAART. The fat loss seemed to involve mainly peripheral regions, while fat accumulation tendency occurred in the trunk.

Underserved populations and bacterial and protozoal sexually transmitted infections: a lost health-care opportunity.

OBJECTIVE: The purpose of our review is an update about the burden of sexually transmitted infections (STIs) among various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. First-line test and treatment based on the latest available evidence according to the revised guidelines of Centers for Disease Control and Prevention have also been considered. MATERIALS AND METHODS: We performed a comprehensive research using scientific databases such as Medline and Pubmed, followed by a review of citations and reference list. A consultation with other experts in the management of the various subpopulations was also conducted. RESULTS: Health-care is often influenced by social determinants, which play a vital role in the diffusion of STIs. The consequence is a socio-economical and ethnic disparity in the rate of STIs. Early screening and treatment of STIs should be implemented in clinical practice, starting from marginalized social groups, which are the most affected by this health problem. CONCLUSIONS: In the literature, there are very few papers containing information on STIs prevalence in various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. The availability of more accurate epidemiological data is needed. In these groups, the most relevant barrier is the lower perception of health-care need, with an underestimation of risk and symptoms of STIs, causing a retard of diagnosis and health-care provision and use. For these populations, targeted interventions are needed, particularly on unaware people, responsible for most STIs transmissions.

The burden of HIV-associated neurocognitive disorder (HAND) in post-HAART era: a multidisciplinary review of the literature.

OBJECTIVE: The purpose of the present multidisciplinary review is to give an updated insight into the most recent findings regarding the pathophysiology, diagnosis and therapeutics of HIV-associated neurocognitive disorder (HAND). MATERIALS AND METHODS: We performed a comprehensive search, through electronic databases (Pubmed - MEDLINE) and search engines (Google Scholar), of peer-reviewed publications (articles and reviews) and conferences proceedings on HAND pathophysiology, diagnosis, and therapy, from 1999 to 2016. RESULTS: It seems to be increasingly clear that neurodegeneration in HIV-1 affected patients is a multi-faceted disease involving numerous factors, from chronic inflammation to central nervous system (CNS) compartmentalization of HIV. Diagnosis of HAND may benefit from both laboratory analysis and advanced specific neuroimaging techniques. As regards HAND therapy, modified HAART combinations and simplification strategies have been tested, while novel exciting frontiers seem to involve the use of nanoparticles with the ability to cross the Blood-Brain Barrier (BBB). CONCLUSIONS: Albeit highly active antiretroviral therapy (HAART) allowed a major decrease in morbidity and mortality for AIDS patients, CNS involvement still represents a challenge in HIV patients even today, affecting up to 50% of patients with access to combination antiretroviral therapy (cART). Future studies will have to focus on CNS compartmentalization, drugs' ability to penetrate and suppress viral replication in this compartment, and on new approaches to reduce HIV-associated neuroinflammation.

Different impact of NNRTI and PI-including HAART on bone mineral density loss in HIV-infected patients.

OBJECTIVE: To evaluate the changes in Bone Mineral Density (BMD) and bone remodelling markers in a group of HIV patients treated with HAART and controlled in a long follow-up and to identify possible risk factors for accelerated bone mass loss. PATIENTS AND METHODS: In a series of 172 HIV patients treated with HAART a total of 67 patients (44 males and 33 females) underwent repeated bone mineral density measurement by DEXA in lumbar spine and in femur; the patients were classified according to T-score WHO criteria. Serum bone alkaline phosphatase (BAP), by IRMA, and urine pyridinoline/deoxypyridinoline (PYD&DPD), by EIA, were also assayed in all cases. RESULTS: At baseline, 62/67 patients were on HAART, while 5 were naïve; 44.8% were previous intravenous drug users (IVDU), 46.3% heterosexual and 8.9% homosexual, mean age being 40.2 ± 6.5 years, and 23.9% had previous AIDS diagnosis. Fifteen/67 (22.4%) of treated patients had osteoporosis and 25/67 (37.3%) osteopenia in spine and/or femur including 3 naïve, 27/67 (40.3%), including 2 naïve, had normal BMD in both sites. Fifty-one/67 patients were monitored during follow-up (56.8 ± 5.3 months); 27 (52.9%) of these (Group 1), received protease inhibitors (PI) and 24 (47.1%), including naïve, (Group 2) received not nucleoside reverse transcriptase inhibitors (NNRTI) for > 50% of follow-up period. In Group 1 patients, BMD reduction was observed after follow-up in respect of basal condition in both spine and femur, but significantly (p = 0.011) only for the latter. However, mean BMD values remained stable in both sites in Group 2 patients. Basal BAP and PYD&DPD levels were higher in Group 1 than Group 2, but not significantly. Moreover, only PYD&DPD levels at the follow-up evaluation were significantly (p = 0.031) higher in Group 1 than Group 2. Of the remaining 16/67 patients with osteoporosis/osteopenia, 10 received PI and 6 NNRTI and were treated with therapies that could increase bone density, in particular, 9 with Alendronate/Vitamin D/Calcium and 7 with only vitamin D/calcium; these patients were excluded from statistical analysis of 51 Group 1/Group 2 cases. In the 16 patients, after these specific treatments, mean spine and femur BMD increased over time, but significantly only in those cases including alendronate in their protocol. CONCLUSIONS: The study showed that in HIV patients on HAART BMD decrease, even osteoporosis, can be present persisting over time, particularly in PI in respect of NNRTI treated patients. The pathogenesis is probably multifactorial, the different antiviral drugs seeming to differently affect bone metabolism. Alendronate/Vitamin D/Calcium therapy can be useful to slow down bone mass loss and also improve osteoporosis/osteopenia conditions, thus, reducing fracture risk also continuing HAART.

HPV infection in HIV-positive females: the need for cervical cancer screening including HPV-DNA detection despite successful HAART.

PURPOSE: To identify the presence of Human Papilloma Virus (HPV) infection and evaluate the role of Highly Active Antiretroviral Treatment (HAART) in patients with HIV-HPV co-infection. We also compared cytological screening results with HPV-DNA detection to implement screening programs and prevention of invasive cervical cancer (ICC) in HIV-infected females. PATIENTS AND METHODS: We enrolled HIV-infected females presenting for routine clinical evaluation. HPV-DNA of high/intermediate and low-risk types was detected from cervical specimens by nucleic acid hybridization assay with signal-amplification. Patients were divided into two groups according to the presence of HPV co-infection (HPV+) or not (HPV-). RESULTS: We enrolled 57 HIV-infected females. Median age was 40 (IQR 35-44) years, mean CD4 count was 547 ± 227 cells/mm(3), 45 (78.9%) had undetectable HIV-RNA and 52 (91.2%) received HAART. Globally, 19/57 (33.3%) patients were HPV-infected, 16/57 (28.1%) with high/intermediate and 3/57 (5.3%) with low-risk types. Five of the 19 (26.3%) HPV+ patients carried both types. Correlating high-risk genotype HPV-DNA detection with cytology, 17.5% of women with negative cytology, 36.4% with ASCUS (Atypical Squamous Cells of Uncertain Significance) and 83.4% of women with positive cytology (50% of LSIL: low-grade squamous intraepithelial lesion and 100% of HSIL: high grade SIL) were HPV positive. No statistical difference when comparing HPV+ and HPV-patients in age, CD4 cell count, in the proportion of previous intravenous-drug use, previous AIDS and of those receiving HAART with undetectable HIV-RNA was observed. CONCLUSIONS: Cervical cancer screening including HPV-DNA detection should be implemented in HIV infected females across Europe, also when receiving successful HAART, to early identify the HIV patients at risk for ICC to be submitted to more frequent follow up and proper treatment.