Prevalence of and risk factors for low bone mineral density in Spanish treated HIV-infected patients.

OBJECTIVES: Several studies have involved antiretroviral therapy in the pathogenesis of low bone mineral density (BMD), while others have not confirmed this association. In this study we analyze the impact of HIV status, traditional risk factors and antiretroviral therapy in BMD in an HIV-infected population living in Madrid. MATERIAL AND METHODS: We performed a cross-sectional analysis of 107 individuals infected with HIV and exposed to antiretroviral treatment to estimate the prevalence of decreased BMD. Bone mineral density of lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry. In a multivariate analysis variables related with HIV status, antiretroviral drugs and traditional risk factors were included. RESULTS: Low BMD was diagnosed in 63 participants (58.9%), including osteoporosis in 11 (10%). At least one cause of osteoporosis was identified in 43 patients (40%), with a deficiency of vitamin D in 86 (89%) and secondary hyperparathyroidism in 30 (28%). In multivariate analysis, increasing age, a treatment based on boosted PI and tenofovir DF, and previous exposure to tenofovir were identified as independent risk factors for a decreased BMD in both lumbar spine and femoral neck. CONCLUSIONS: We have confirmed a high prevalence of reduced BMD, which is favoured by ritonavir-boosted PI and TDF. Bone safety should continue to be evaluated in clinical trials and cohort studies in order to demonstrate that the new drugs offer additional advantages regarding the impact on BMD.

[Predictive factors of clinically significant drug-drug interactions among regimens based on protease inhibitors, non-nucleoside reverse transcriptase inhibitors and raltegravir]. / Factores predictivos de las interacciones farmacológicas clínicamente significativas en los pacientes tratados con regímenes basados en inhibidores de proteasa, inhibidores de transcriptasa inversa no nucleósidos y raltegravir.

BACKGROUND AND OBJECTIVE: To determine the prevalence and types of clinically significant drug-drug interactions (CSDI) in the drug regimens of HIV-infected patients receiving antiretroviral treatment. DESIGN: retrospective review of database. Centre: Hospital Universitario Severo Ochoa, Infectious Unit. PARTICIPANTS: one hundred and forty-two participants followed by one of the authors were selected from January 1985 to December 2014. DATA COLLECTION: from their outpatient medical records we reviewed information from the last available visit of the participants, in relation to HIV infection, comorbidities, demographics and the drugs that they were receiving; both antiretroviral drugs and drugs not related to HIV infection. We defined CSDI from the information sheet and/or database on antiretroviral drug interactions of the University of Liverpool (http://www.hiv-druginteractions.org) and we developed a diagnostic tool to predict the possibility of CSDI. By multivariate logistic regression analysis and by estimating the diagnostic performance curve obtained, we identified a quick tool to predict the existence of drug interactions. RESULTS: Of 142 patients, 39 (29.11%) had some type of CSDI and in 11.2% 2 or more interactions were detected. In only one patient the combination of drugs was contraindicated (this patient was receiving darunavir/r and quetiapine). In multivariate analyses, predictors of CSDI were regimen type (PI or NNRTI) and the use of 3 or more non-antiretroviral drugs (AUC 0.886, 95% CI 0.828 to 0.944; P=.0001). The risk was 18.55 times in those receiving NNRTI and 27,95 times in those receiving IP compared to those taking raltegravir. CONCLUSIONS: Drug interactions, including those defined as clinically significant, are common in HIV-infected patients treated with antiretroviral drugs, and the risk is greater in IP-based regimens. Raltegravir-based prescribing, especially in patients who receive at least 3 non-HIV drugs could avoid interactions.

[Aging and influence of inversion of the CD4:CD8 ratio in the incidence of co-morbidities and mortality in a cohort of patients infected with human immunodeficiency virus]. / Envejecimiento e influencia de la inversión del cociente CD4/CD8 en la incidencia de las comorbilidades y mortalidad de una cohorte de pacientes infectados por el virus de inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: It has been postulated that the inversion of the CD4:CD8 ratio as a hallmark of immunosenescence can be an independent factor that can herald the risk of co-morbidities. We studied the influence of aging and inversion of the CD4:CD8 ratio in the incidence of comorbidities and mortality in the cohort of Hosptital Severo Ochoa. METHODS: We analyzed the differences in the incidence rates of age-adjusted morbidities and evaluated the inversion of the CD4:CD8 ratio as predictor of mortality and development of comorbidities. RESULTS: Age was associated with an increased incidence rate of diabetes mellitus, fractures, COPD and non-AIDS malignancies. We found an increased incidence rate of non-AIDS clinical events (OR 2.25; 95% CI 1.025-4.94) and AIDS events (OR 3.48; 95% CI 1.58-7.64) in individuals with CD4:CD8 ratio<0.7. Moreover, patients with a CD4:CD8 ratio<0.7 ratio had a higher risk of mortality (OR 5.96; 95% CI 0.73 to 48.40). CONCLUSION: It is important to detect and prevent non-AIDS comorbidities in the presence of a CD4:CD8 ratio<0.7.

Prevalence of vitamin D deficiency and its related risk factor in a Spanish cohort of adult HIV-infected patients: effects of antiretroviral therapy.

We analyzed serum 25(OH) cholecalciferol [25(OH)D] levels and factors related to deficiency (<20 ng/ml) or insufficiency (<30 ng/ml) in a cohort of Spanish HIV-infected patients and compared them with an age- and latitude-matched population from another study. We prospectively assessed 25(OH)D deficiency/insufficiency in a cohort of 352 HIV patients during 2009-2010. Predisposing factors were recorded and their relationship to low levels was assessed by logistic regression; a nutritional survey examined intake, nutritional status, and sunlight exposure in a subgroup of 92 patients. We studied the correlation of 25(OH)D with parathyroid hormone (PTH) and alkaline phosphatase. Age-, sex-, and race/ethnicity-adjusted vitamin D deficiency (<20 ng/ml) was 44.0% (95% CI, 38.8-49.4%) and insufficiency (<30 ng/ml) was 71.6% (95% CI, 66.9-76.3). Deficiency was 16.4% more prevalent in our sample than in non-HIV-infected Spaniards. Lower sunlight exposure was the only factor related to lower levels in the lifestyle and nutritional survey (p=0.045). In multiple logistic regression, higher body mass index (BMI), black race/ethnicity, lower seasonal sunlight exposure, men who have sex with men (MSM), and heterosexual transmission categories, efavirenz exposure and lack of HIV viral suppression were independently associated with deficiency/insufficiency. These variables predicted 79% of cases [AUC=0.872 (95% CI, 0.83-0.91)]. Patients receiving protease inhibitors (PIs) [OR 4.0 (95% CI, 1.3-12.3); p=0.014] or NNRTI [OR 3.6 (95% CI, 1.7-11.2); p=0.025] had higher odds of increased PTH levels; this was significant only in 25(OH)D-deficient patients (p=0.004). As in less insolated areas, the prevalence of vitamin D deficiency/insufficiency was high in HIV-infected patients in Spain; among treated patients, levels were higher with PIs than with efavirenz.

[Efficacy and safety of a reduced-dose of stavudine in HIV-infected patients under immunological and virological stable conditions]. / Impacto de la reducción de dosis de estavudina en su perfil de eficacia/seguridad en pacientes con infección por el virus de la inmunodeficiencia humana inmunológica y virológicamente estables.

BACKGROUND AND OBJECTIVE: Stavudine (d4T) has shown a favourable short and long-term tolerability profile. Nevertheless, its usage is currently decreasing due to some safety concerns. We aimed to evaluate the efficacy and safety of d4T low-dose-based regimens. PATIENTS AND METHOD: This was a multicenter and retrospective review chart of patients receiving standard doses of d4T for > or = 6 months (weight > 60 kg: 40 mg/12 h; weight < 60 kg: 30 mg/12 h) and having undetectable viral load for at least 3 months before the d4T dose reduction (weight > 60 kg: 30 mg/12 h; weight < 60 kg: 20 mg/12 h). Immunological and viral parametres, lipid profile and side effects were determined. RESULTS: A total of 982 patients were included. The main reason for reducing the dose was prevention of toxicity (76%). After 6 months of follow-up, 97% and 84% patients had less than 400 and 50 cp/ml, respectively, and the CD4 cell count increased by 38 cel/ml. Lipids, lipodystrophy and peripheral polineuropathy improved but there was no statistical significance. CONCLUSIONS: A d4T dose reduction in an immuno-virologically stable population does not affect treatment efficacy. Longer follow-ups are required to confirm improvements in the safety profile.