Open AccessLamivudine plus a boosted‐protease inhibitor as simplification strategy in HIV‐infected patients with toxicity to nucleoside analogues
Author(s) -
Casado J,
De la Calle C,
Del Palacio M,
Bañon S,
Pérez Elías M,
Moreno A,
Moreno S
Publication year - 2012
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.7448/ias.15.6.18382
Subject(s) - medicine , ritonavir , lamivudine , lopinavir , darunavir , gastroenterology , didanosine , indinavir , toxicity , nucleoside analogue , viral load , pharmacology , virology , nucleoside , antiretroviral therapy , virus , biology , hepatitis b virus , biochemistry
Purpose of the study Dual therapy with lamivudine plus a PI boosted with ritonavir (PI/r) could be an alternative to standard triple therapy or PI/r monotherapy as a simplification strategy in patients with toxicity to nucleoside analogues (NA). Methods Retrospective cohort study of 44 HIV‐infected patients on suppressive HAART, with no chronic HBV, who simplified to this dual therapy since 2008. Virological and immunological outcome, lipids and renal changes were evaluated. Summary of results Mean age was 50 years (38‐70), 66% were male, and the median time of HIV infection was 18.6 years. The median nadir CD4+ count was 150 cells/ml (2–407). At inclusion, patients were receiving therapy with lamivudine plus atazanavir/r in 5 cases, lopinavir/r in 12, and darunavir/r in 27, and they had an HIV RNA level<50 copies/ml for a median time of 794 days (129–2344, 90% >6 months). The NA discontinued was tenofovir (27), didanosine (12), AZT (3), and d4T (2). The reasons for changing were toxicity in 76% of cases, especially renal impairment. They had received a mean of 8 regimens before (2–20), and 55% were in CDC‐stage C. In 11 cases, history of resistance was available (to NA in 7 cases, including the 210W mutation in four). The mutations 184V was not observed, but four patients (9%) had a previous failure to therapy including 3tC. Mutations in the protease gene were observed in 8 patients (2 to 7 mutations, the most frequent 77I and 93L), without resistance to the current PI/r. During 62.8 patient‐years of follow‐up (median, 802 days), only 2 patients failed (4.5%), due to incomplete adherence, at 27 and 141 days. Of note, these two patients had no previous failed with 3tC or PI. Overall, CD4+ count increased for 55 cells/ml. No new adverse events were observed, but total cholesterol (from 180 to 246 mg/dl, p=0.007) and triglycerides (from 166 to 195, p=0.01) increased during the first 24 weeks with improvement at 48 weeks. On the other hand, estimated glomerular filtration rate improved during follow up (from 74.2 ml/min to 83.08 ml/min after 48 weeks, p=0.1). Conclusions Dual therapy with lamivudine plus a boosted PI is safe and effective as simplification strategy in patients with toxicity to NA. This combination could be an alternative to mono or triple therapy in hard to treat patients, although an initial increase in lipid parameters could be observed.