Impact of hypogonadism on bone mineral density and vertebral fractures in HIV-infected men.

PURPOSE: Hypogonadism and osteoporosis are frequently reported in HIV-infected men and, besides multifactorial pathogenesis, they might be directly linked because of testicular involvement in bone health. We evaluated the prevalence of osteoporosis and vertebral fractures (VFs) in HIV-infected men, and assessed their relationship with gonadal function. METHODS: We enrolled 168 HIV-infected men (median age 53). Osteoporosis and osteopenia were defined with T-score ≤ - 2.5SD and T-score between - 1 and - 2.5SD, respectively. VFs were assessed by quantitative morphometric analysis. Total testosterone (TT), calculated free testosterone (cFT), Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) were obtained; overt hypogonadism was defined on symptoms and low TT or cFT, and classified into primary and secondary according to gonadotropins; compensated hypogonadism was defined as normal TT and cFT with high LH levels. RESULTS: Overall, osteoporosis and osteopenia were found in 87.5% of patients, and VFs were detected in 25% of them; hypogonadism was identified in 26.2% of cases. Osteoporotic patients had higher SHBG vs those with normal bone mineral density (BMD). Fractured patients were more frequently hypogonadal and with higher SHBG. SHBG showed negative correlation with both spine and femoral BMD, and positive correlation with VFs. In multivariate models, FSH showed negative impact only on femoral BMD, whereas older age and higher SHBG predicted VFs. CONCLUSION: We found a high burden of bone disease and hypogonadism in HIV-infected men, and we showed that the impact of gonadal function on bone health is more evident on VFs than on BMD.

Hypogonadism and liver fibrosis in HIV-infected patients.

PURPOSE: Hypogonadism is frequent in HIV-infected men and might impact on metabolic and sexual health. Low testosterone results from either primary testicular damage, secondary hypothalamic-pituitary dysfunction, or from liver-derived sex-hormone-binding-globulin (SHBG) elevation, with consequent reduction of free testosterone. The relationship between liver fibrosis and hypogonadism in HIV-infected men is unknown. Aim of our study was to determine the prevalence and type of hypogonadism in a cohort of HIV-infected men and its relationship with liver fibrosis. METHODS: We performed a cross-sectional retrospective study including 107 HIV-infected men (median age 54 years) with hypogonadal symptoms. Based on total testosterone (TT), calculated free testosterone, and luteinizing hormone, five categories were identified: eugonadism, primary, secondary, normogonadotropic and compensated hypogonadism. Estimates of liver fibrosis were performed by aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) scores. RESULTS: Hypogonadism was found in 32/107 patients (30.8%), with normogonadotropic (10/107, 9.3%) and compensated (17/107, 15.8%) being the most frequent forms. Patients with secondary/normogonadotropic hypogonadism had higher body mass index (BMI) (p < 0001). Patients with compensated hypogonadism had longer HIV infection duration (p = 0.031), higher APRI (p = 0.035) and FIB-4 scores (p = 0.008), and higher HCV co-infection. Univariate analysis showed a direct significant correlation between APRI and TT (p = 0.006) and SHBG (p = 0.002), and between FIB-4 and SHBG (p = 0.045). Multivariate analysis showed that SHBG was independently associated with both liver fibrosis scores. CONCLUSION: Overt and compensated hypogonadism are frequently observed among HIV-infected men. Whereas obesity is related to secondary hypogonadism, high SHBG levels, related to liver fibrosis degree and HCV co-infection, are responsible for compensated forms.

Predictors of incomplete viral response and virologic failure in patients with acute and early HIV infection. Results of Italian Network of ACuTe HIV InfectiON (INACTION) cohort.

OBJECTIVES: The aim of this study was to evaluate the factors that can influence an incomplete viral response (IVR) after acute and early HIV infection (AEHI). METHODS: This was a retrospective, observational study including patients with AEHI (Fiebig stages I-V) diagnosed between January 2008 and December 2014 at 20 Italian centres. IVR was defined by: (1) viral blip (51-1000 HIV-1 RNA copies/mL after achievement of < 50 HIV-1 RNA copies/mL); (2) virologic failure [> 1000 copies/mL after achievement of < 200 copies/mL, or ≥ 200 copies/mL after 24 weeks on an antiretroviral therapy (ART)]; (3) suboptimal viral response (> 50 copies/mL after 48 weeks on ART or two consecutive HIV-1 RNA levels with ascending trend during ART). Cox regression analysis was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for IVR. RESULTS: In all, 263 patients were studied, 227 (86%) males, with a median [interquartile range (IQR)] age of 38 (30-46) years. During a median follow-up of 13.0 (5.7-31.1) months, 38 (14.4%) had IVR. The presence of central nervous system (CNS) symptoms was linked to a higher risk of IVR (HR = 4.70, 95% CI: 1.56-14.17), while a higher CD4/CD8 cell count ratio (HR = 0.13, 95% CI: 0.03-0.51 for each point increase) and first-line ART with three-drug regimens recommended by current guidelines (HR = 0.40, 95% CI: 0.18-0.91 compared with other regimens including four or five drugs, older drugs or non-standard backbones) were protective against IVR. CONCLUSIONS: Patients with lower CD4/CD8 ratio and CNS symptoms could be at a higher risk of IVR after AEHI. The use of recommended ART may be relevant for improving short-term viral efficacy in this group of patients.

Survival in HIV-infected patients with lymphoma according to the choice of antiretroviral treatment: an observational multicentre study.

OBJECTIVES: Lymphoproliferative disorders are often observed in HIV-positive patients. Combination antiretroviral treatment (cART) during antineoplastic chemotherapy is beneficial, but little is known about the clinical outcome according to different antiretroviral combinations. The aim of the study was to address this gap in current knowledge. METHODS: A retrospective study was conducted in five large Italian centres for the period from 1998 to 2015; HIV-positive patients diagnosed with lymphoma were included and demographic, clinical and therapeutic variables were recorded and associated with clinical outcomes. Bivariate and multivariate analyses were performed, including Cox proportional hazard models for survival. RESULTS: A total of 399 patients were included in the study. The most common types of lymphoma were diffuse large B-cell lymphoma (DLCLB; n = 164), Hodgkin lymphoma (HL; n = 99) and Burkitt lymphoma (BL; n = 57), followed by plasmablastic lymphoma (PBL; n = 38), T-cell lymphoma (TCL; n = 17), indolent lymphoma (n = 10) and other less common types (n = 14). cART was given to 327 (out of 387 evaluable) patients: in 216 subjects it was protease inhibitor (PI)-based, in 73 it was nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and in 18 it was integrase strand transfer inhibitor (INSTI)-based (the remaining 20 individuals received other regimens). The 5-year overall survival was 57.5% (52.8% for DLCLB, 67.8% for HL, 42.3% for BL, 60.6% for PBL and 64.7% for TCL). PI-based ART compared with other compounds was associated with worse survival in non-Hodgkin lymphoma (NHL) and HL patients combined (P ≤ 0.001) and in NHL patients alone (P < 0.001); grade 3-4 haematological toxicities were more commonly observed in PI-treated individuals. Lymphoma diagnosis in recent years, better immunovirological status, lower lymphoma stage and better prognostic indexes were associated with better survival. CONCLUSIONS: PI-based cART while on chemotherapy was associated with worse overall survival and more frequent haematological complications in HIV-positive patients with lymphoma.

The increasing burden and complexity of multi-morbidity and polypharmacy in geriatric HIV patients: a cross sectional study of people aged 65 - 74 years and more than 75 years.

BACKGROUND: Geriatric Patients Living with HIV/AIDS (GEPPO) is a new prospective observational multicentre cohort consisting of all the HIV-positive geriatric patients being treated at 10 clinics in Italy, and HIV-negative controls attending a single geriatric clinic. The aim of this analysis of the GEPPO cohort was to compare prevalence and risk factors of individual non-communicable diseases (NCD), multi-morbidity (MM) and polypharmacy (PP) amongst HIV positive and HIV negative controls at enrolment into the GEPPO cohort. METHODS: This cross-sectional study was conducted between June 2015 and May 2016. The duration of HIV infection was subdivided into three intervals: < 10, 10-20 and > 20 years. The NCD diagnoses were based on guidelines defined criteria, including cardiovascular disease, hypertension, type 2 diabetes, chronic kidney disease, dyslipidaemia, chronic obstructive pulmonary disease. MM was classified as the presence of two or more co-morbidities. The medications prescribed for the treatment of comorbidities were collected in both HIV positive and HIV negative group from patient files and were categorized using the Anatomical Therapeutic Chemical (ATC) classification. PP was defined as the presence of five or more drug components other than anti-retroviral agents. RESULTS: The study involved a total of 1573 patient: 1258 HIV positive and 315 HIV negative). The prevalence of individual comorbidities was similar in the two groups with the exception of dyslipidaemia, which was more frequent in the HIV-positive patients (p <  0.01). When the HIV-positive group was stratified based on the duration of HIV infection, most of the co-morbidities were significantly more frequent than in control patients, except for hypertension and cardiovascular disease, while COPD was more prevalent in the control group. MM and PP were both more prevalent in the HIV-positive group, respectively 64% and 37%. CONCLUSIONS: MM and PP burden in geriatric HIV positive patients are related to longer duration of HIV-infection rather than older age per se.

Role of bone mineral density in predicting morphometric vertebral fractures in patients with HIV infection.

UNLABELLED: This study investigated the bone of HIV patients both in terms of quantity and quality. It was found that HIV-infected patients did fracture independently of the degree of bone demineralization as in other forms of secondary osteoporosis. INTRODUCTION: We aimed to determine the prevalence of vertebral fractures (VFs) in HIV patients who were screened by bone mineral density (BMD) and to explore possible factors associated with VFs. METHODS: This is a cross-sectional study that included HIV-infected patients recruited in the Clinic of Infectious and Tropical Diseases and that underwent BMD measurement by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and hip (Lunar Prodigy, GE Healthcare). For the assessment of VFs, anteroposterior and lateral X-ray examinations of the thoracic and lumbar spines were performed and were centrally digitized. Logistic regression models were used in the statistical analysis of factors associated with VFs. RESULTS: One hundred thirty-one consecutive patients with HIV infection (93 M, 38 F, median age 51 years; range, 36-75) underwent BMD measurement: 25.2 % of patients showed normal BMD, while 45 % were osteopenic and 29.7 % osteoporotic. Prevalence of low BMD (osteopenia and osteoporosis) was higher in females as compared to males (90 vs 69 %) with no significant correlation with age and body mass index. VFs occurred more frequently in patients with low BMD as compared to patients with normal BMD (88.5 vs. 11.4 %; p < 0.001) without any significant difference between osteopenia and osteoporosis (43 vs. 46 %; p = 0.073). VFs were significantly associated with older age and previous AIDS events. CONCLUSIONS: These results suggest a BMD <-1 threshold to identify patients at risk of skeletal fragility and, therefore, good candidates for morphometric evaluation of spine X-ray in line with other forms of secondary osteoporosis with impaired bone quality.

Kidney disease in HIV-infected patients.

The introduction of highly active antiretroviral therapy (HAART) has reduced mortality and improved life expectancy of HIV-positive patients. However, increased survival is associated with increased prevalence of comorbidities, such as cardiovascular disease, hepatic and renal disease. Kidney disease, including HIV-associated nephropathy, acute renal failure and chronic kidney disease, represents one of the main causes of morbidity and mortality, especially if associated to other risk factors, i.e. hypertension, diabetes, older age, black race and hepatitis C coinfection. Careful evaluation of renal function may help identifying kidney disease in its early stages. In addition, proper management of hypertension and diabetes is recommended. Even if HAART has changed the natural course of HIV-associated nephropathy, reducing the risk of End-stage Renal Disease (ERDS), some antiretroviral regimens have been related with the development of acute or chronic kidney disease. Further studies are needed to optimize the management of renal disease among HIV-infected patients.

Vitamin D deficiency in HIV infection: an underestimated and undertreated epidemic.

Hypovitaminosis D is a very common disorder, regarding both Western and developing countries. A growing amount of data over the last years have shown vitamin D deficiency to be high prevalent among HIV-positive subjects. In addition to "classic" risk factors, such as female sex, low dietary intake, dark skin pigmentation and low sun exposure, HIV-related factors, including immune activation and antiretroviral adverse effects, may affect vitamin D status. Even if both protease inhibitors and non-nucleoside reverse transcriptase inhibitors have been associated with low vitamin D levels, available evidences have failed to univocally associate hypovitaminosis D with specific antiretroviral class effects. Low vitamin D is known to have a negative impact not only on bone health, but also on neurocognitive, metabolic, cardiovascular and immune functions. Similarly to the general population, several studies conducted on HIV-infected subjects have associated hypovitaminosis D with a greater risk of developing osteopenia/osteoporosis and fragility fractures. Analogously, vitamin D deficiency has been described as an independent risk factor for cardiovascular disease and metabolic disorders, such as insulin resistance and type 2 diabetes mellitus. Last EACS guidelines suggest to screen for hypovitaminosis D every HIV-positive subject having a history of bone disease, chronic kidney disease or other known risk factors for vitamin D deficiency. Vitamin D repletion is recommended when 25-hydroxyvitamin D levels are below 10 ng/ml. Furthermore, it may be indicated in presence of 25OHD values between 10 and 30 ng/ml, if associated with osteoporosis, osteomalacia or increased parathyroid hormone levels. The optimal repletion and maintenance dosing regimens remain to be established, as well as the impact of vitamin D supplementation in preventing comorbidities.

[HIV/AIDS care and international migrations in the rural district of Nanoro, Burkina Faso]. / Prise en charge du VIH/sida et migrations internationales dans le district rural de Nanoro, Burkina Faso.

West African Countries account for almost half of the estimated 20 000 000 international migrants in the continent. In the frame of the scaling up of HAART, our study aims to identify specific features and constraints of access to care for HIV migrant patients returning to Burkina Faso. From January 2007 to August 2011, the Nanoro District Hospital, serving a rural area in the Centre-West of Burkina Faso, followed 437 HIV/AIDS adult patients. Migrants were 139/437 (31.8 %), of whom 108/139 (77.7 %), declared they returned to Burkina Faso to seek care, because the area they migrated to did not offer specific HIV health assistance. At baseline, 113/139 (81,3 %) migrants and 181/298 (60,7 %) residents were in WHO clinical stages III or IV (p< 0.01). For every 100 patients/ year under HAART, 25.5 migrants (91.4 % of whom to foreign countries) and 5.7 Burkina residents were transferred to other centers (p<0.01). 21.8 migrants and 8.5 residents were dead or lost to follow up (p<0.05). For migrant patients, access to HIV screening and care seems to be delayed. The high frequency of migrants under HAART working abroad requires an improved cooperation among the health systems of the African Countries.

P. falciparum malaria recrudescence in a cancer patient.

Persons living for long periods of time in malaria hyper-endemic areas may suffer from hyper-reactive malarial splenomegaly (HMS), a frequent cause of splenomegaly in such areas. Splenomegaly and sub-microscopic P. falciparum parasitaemia are hallmarks of HMS. Spleen has been suggested to play a protective antimalarial role and splenectomy may trigger symptomatic malaria attacks. Other causes of immune suppression may possibly reactivate latent malaria parasites. We report the case of an Italian 60-year-old male, who had spent 33 years in sub-Saharan Africa, who experienced a P. falciparum malaria attack 12 months after his return to Italy, concomitantly with a diagnosis of lung carcinoma possibly impairing his immune system.