Juan A. Arroyo

Risk of Metabolic Abnormalities in Patients Infected with HIV Receiving Antiretroviral Therapy that Contains Lopinavir-Ritonavir

The evolution of fasting glucose, triglyceride, and total and high-density lipoprotein (HDL) cholesterol level and the factors associated with development of clinically significant abnormalities in these metabolic parameters at 6 months were assessed in 353 consecutive human immunodeficiency virus (HIV)-infected patients who were receiving antiretroviral therapy containing lopinavir-ritonavir. Although glucose and HDL cholesterol levels did not change, triglyceride and total cholesterol levels significantly increased (P<.0001 for each), as did the proportion of patients with a triglyceride level of >400 mg/dL and a total cholesterol level of >240 mg/dL (P=.002). A baseline triglyceride level of >400 mg/dL and a baseline total cholesterol level of >240 mg/dL were identified as independent factors predicting clinically significant hypertriglyceridemia and hypercholesterolemia, respectively, at 6 months. These findings may have clinical implications when the therapeutic option of lopinavir-ritonavir is considered.

Switching to Nevirapine Decreases Insulin Levels but Does Not Improve Subcutaneous Adipocyte Apoptosis in Patients with Highly Active Antiretroviral Therapy–Associated Lipodystrophy

Subcutaneous adipocyte apoptosis occurs in lipotrophic areas of patients with highly active antiretroviral therapy (HAART)-associated lipodystrophy. Fourteen patients with HAART-associated lipodystrophy had 2 subcutaneous biopsies for evidence of adipocyte apoptosis, the second after a randomized change to nevirapine (n=8) or after remaining on a regimen of indinavir-based HAART (n=6). Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP-digoxigenin nick end-labeling method. Patients who were switched to nevirapine had a significant decrease in insulinemia and a significant increase in the glucose:insulin ratio. Overall, subcutaneous adipocyte apoptosis increased in 3 patients who were switched to nevirapine and in 3 who continued to receive indinavir but decreased in 2 patients switched to nevirapine and another 2 who continued to receive indinavir. Subcutaneous adipocyte apoptosis continues to occur in lipotrophic areas of patients with HAART-associated lipodystrophy despite switching from indinavir to nevirapine, suggesting that such a strategy will be useless for reversal of lipoatrophy.

Bilateral Bell Palsy and Acute HIV Type 1 Infection: Report of 2 Cases and Review

Two adult patients who presented to a hospital with bilateral facial Bell palsy who were also experiencing human immunodeficiency virus type 1 seroconversion are described. Ten additional cases retrieved from the literature are also reviewed. Bell palsy appeared a median of 15 days after the beginning of the clinical disease, and aseptic meningitis was an invariable concomitant of facial neuropathy. All but 1 patient (8.3%) recovered without sequelae.

Identification of a novel mutation in the ANGPTL3 gene in two families diagnosed of familial hypobetalipoproteinemia without APOB mutation

BACKGROUND Familial hypobetalipoproteinemia (FHBL), characterized by extremely low levels of plasma apolipoprotein (apo) B and cholesterol associated with low-density lipoproteins (LDLc), is considered to be an autosomal co-dominant disorder of heterogeneous origin. The main genetic disorder associated with FHBL consists of mutations in the APOB gene, while other less frequent forms are associated with mutations in NPC1L1, PCSK9, a still unidentified gene in 3p21.1-22 and, more recently, in ANGPTL3. METHODS We scanned for ANGPTL3 mutations in 4 unrelated Spanish families with FHBL criteria but negative for mutations in APOB. The entire coding region and intron-exon boundaries of the ANGPTL3 gene were amplified and sequenced. RESULTS Two probands were positive for the same frameshift mutation, a deletion of 5 bp in codon 121 in ANGPTL3, which produces a truncated protein of 122 residues. This mutation in homozygosis was associated in both families with combined hypolipidemia, characterized by low plasma apoB, low total, LDL and HDL cholesterol and low triglycerides. CONCLUSION We confirm the existence of a new phenotype of FHBL, denominated familial combined hypolipidemia, which consist of a biochemical phenotype of low LDLc, low apoB, low TG and, unlike APOB mutations, low HDL cholesterol, due to a loss-of-function mutation in ANGPTL3.

Failure of cetirizine to prevent nevirapine-associated rash: a double-blind placebo-controlled trial for the GESIDA 26/01 Study.

ObjectivesRash is the most frequent adverse event associated with nevirapine. The use of antihistamines remains unclear in this setting. A double-blind placebo-controlled study was performed to evaluate the efficacy of cetirizine in the prevention of nevirapine rash. MethodsA multicenter, randomized, double-blind, placebo-controlled clinical trial with cetirizine (10 mg/d × 30 days) was conducted. Inclusion criteria were HIV-1 infection and nevirapine therapy started with any CD4 cell count or plasma viral load and without simultaneous use of abacavir, cotrimoxazole, or rifampin. Clinical follow-up was performed at 15, 30, and 90 days. ResultsTwo hundred seventeen evaluable patients were enrolled (107 patients receiving cetirizine and 110 patients receiving placebo), 32.3% of whom were women. The median baseline CD4 cell count and plasma viral load were 341 cells/mm3 and 11,000 copies/mL, respectively. Overall, 29 rashes (13.4%) were detected: 16 (15.0%) in the cetirizine group and 13 (11.8%) in the placebo group (odds ratio [OR] = 1.31, 95% confidence interval [CI]: 0.60–2.88; P = 0.50). The incidence of moderate to severe rashes leading to nevirapine withdrawal was 10.3% (11 of 107 patients) in the cetirizine group and 7.3% (8 of 110 patients) in the placebo group (OR = 1.46, 95% CI: 0.52–4.18; P = 0.43). Adverse events leading to withdrawal of therapy appeared in 14 patients (13.1%) from the cetirizine group and 10 (9.1%) from the placebo group (P = 0.34). ConclusionCetirizine does not prevent the incidence or affect the severity of nevirapine-associated rash.

Diferencias en la reducción de la presión arterial en función de la toma de la medicación en horario diurno o nocturno

BACKGROUND AND OBJECTIVE In this study, 123 recordings of blood pressure (BP) obtained by ambulatory BP monitoring were analyzed. These recordings were measured in 2011 in patients from a Spanish tertiary university hospital. All participating patients were treated with 2, 3 or 4 anti-hypertensive drugs. The main aim of this study was to determine differences in BP control, if any, depending on the medication schedule. Thus, BP levels were studied at 3 periods of the day: activity hours, rest hours and 24h. PATIENTS AND METHOD We compared subjects taking all anti-hypertensive agents during the day (n=70, group 1) with those taking at least one at night (n=53, group 2). RESULTS Significant differences were found on diastolic BP, where group 2 patients had lower levels at activity, 24h periods and sleep-time. Even if it was not statistically significant, lower levels of systolic BP from group 2 were also observed at activity and 24h periods as well as lower levels of systolic, diastolic and mean BP at rest hours periods. There were also significant group differences in relation to the number of prescribed agents (with the mean being higher for group 2) and the type of agent (beta-blockers and calcium antagonists were more prevalent in group 2). Nevertheless, the multivariate regression analysis done taking into account these variables did not change the observed statistical significance. CONCLUSION The administration of anti-hypertensive drugs at night could be associated with lower BP levels.