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Biomedical subjects

Francisco Blanco

Publications and source records attributed to Francisco Blanco.

21 records · Page 2Linked to original sources

Hydroxyurea plus didanosine as maintenance therapy for HIV-infected patients on long-term successful highly active antiretroviral therapy.

BACKGROUND: Toxicity and quality of life issues have moved to delay the initiation of highly active antiretroviral therapy (HAART) and to explore novel treatment strategies for HIV infection. The switch to simpler regimens or treatment discontinuation has been attempted with limited success. The combination of hydroxyurea (HU) plus didanosine (ddI) is a simple regimen that might be able to restrain virus replication for long periods of time and could be an acceptable option as maintenance therapy in patients on prolonged successful HAART. METHOD: The combination of HU (500 mg bid) plus ddI (400 mg qd) was offered to participants with viral load (VL) <50 HIV RNA copies/mL and CD4 counts >350 cells/microL for more than 6 months under HAART. The prior HAART regimen was resumed if VL rose to >5,000 copies/mL and/or the CD4 count fell to <200 cells/microL after being on HU + ddI maintenance therapy. RESULTS: A total of 187 participants replaced HAART with HU + ddI. In an intent-to-treat analysis at 48 weeks, 109 (58%) and 77 (41%) patients had VL below 5,000 and 500 HIV RNA copies/mL, respectively. The mean CD4 count dropped from 809 +/- 283 to 573 +/- 270 cells/microL, while 77% of patients remained above 350 cells/microL. The proportion of participants with hypercholesterolemia declined from 70% to 46% (p <.001), while those with hypertriglyceridemia fell from 36% to 21% (p <.05). Significant improvements in lipohypertrophy and lipoatrophy were observed in 52% and 64% of participants, respectively. Grade 3-4 toxicities appeared in 20 patients (11%), including 3 cases of pancreatitis and 1 of peripheral neuropathy. Prior history of VL >5 log, CD4 counts <200 cells/microL, and ddI experience were independently associated with lower response to HU + ddI maintenance therapy. CONCLUSION: The combination of HU + ddI may be a satisfactory maintenance therapy for more than half of patients on successful HAART who want to alleviate drug-related toxicities and/or pill burden. Patients with metabolic and/or body-shape abnormalities might particularly benefit from switching to this simple regimen.

Adult↗

Avascular necrosis in HIV-infected patients receiving antiretroviral treatment: study of seven cases.

PURPOSE: We analyzed clinical, radiological, scintigraphical, epidemiological, and immunological data in a group of HIV-infected patients with osteonecrosis. METHOD: The first case was diagnosed in June 1997, and 6 more were identified thereafter among 1,650 attended patients (0.36%). Mean age was 37.6 years (33-46), and all were men. Mean CD4+ lymphocyte count was 501 cells/microL (98-1156), viral load was undetectable (<50 copies/mL) in 5 patients, and only 2 had AIDS diagnosis. Two patients were alcohol abusers, 1 received corticosteroids, and 3 had hypertrigliceridemia. One patient was treated with d4T plus 3TC, and the remaining received HAART. In 2 patients, lipodystrophy was simultaneously diagnosed. RESULTS: Mean time between first dose of antiretroviral drugs and onset of symptoms was 12 months (2-24). All patients developed pain and functional impotence of the affected joints, and the diagnosis was confirmed by imaging techniques. Distribution of the affected sites was as follows: both hips in 5 cases, femoral external condyle in 1, and multiple joints in 1. In 4 cases, the protease inhibitor was interrupted; there was clinical improvement in 2 of these cases. The unfavorable outcome of the remaining cases required surgical intervention. CONCLUSION: Metabolic and bone diseases should be considered a complication of HIV infection that is of growing importance.

Adult↗

First-line therapy and mitochondrial damage: different nucleosides, different findings.

BACKGROUND: Antiretroviral therapy has been associated with the development of morphologic body-shape changes and metabolic abnormalities, including dislipemia, insulin resistance, and hyperlactatemia. Mitochondrial damage secondary to the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) has been related to some of these complications, although the role of different NRTIs in their development is not well established. OBJECTIVES: To assess the incidence of hyperlactatemia and lipodystrophy body-shape changes in drug-naïve HIV-infected patients who began highly active antiretroviral therapy (HAART) based on a backbone of two different NRTI combinations. METHOD: Prospective, longitudinal, observational study of all consecutive drug-naïve HIV-infected individuals who started HAART with zidovudine (AZT) plus lamivudine (3TC) or didanosine (ddI) plus stavudine (d4T) between June 2000 and June 2001 at one single institution. Serum lactate levels and lipodystrophy body-shape changes were monitored periodically during 12 months. RESULTS: At 1 year, mean lactate values remained <2 mmol/L in all 26 patients who received AZT+3TC, but they significantly increased (mean, 2.6 mmol/L) in 50 patients treated with ddI+d4T. The percentage of patients with hyperlactatemia (lactate >or=2 mmol/L) steadily increased in those on ddI+d4T (from 30% at 3 months to 71% at 12 months), whereas it remained below 10% in patients treated with AZT+3TC. Two patients on ddI+d4T developed lactic acidosis. Mean serum lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), and amylase significantly increased in patients treated with ddI+d4T, whereas they remained unaltered in patients under AZT+3TC. Significant correlations were found between lactate and LDH, alkaline phosphatase (AP), and GGT. In the multivariate analysis, treatment with ddI+d4T, LDH, and AP was significantly associated with lactate levels. At 12 months, subcutaneous lipoatrophy was significantly more frequent in patients treated with ddI+d4T than in those on AZT+3TC (35% vs. 8%; p =.01). CONCLUSION: In drug-naïve HIV-infected patients who start antiretroviral therapy, ddI+d4T-based combinations produce a greater increase in serum lactate and lipoatrophy than therapies based on AZT+3TC within the first year of therapy. An increase in LDH, amylase, GGT, and AP levels may signal an increase in lactate, which may be harmful.

Adult↗