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The liver safety of tenofovir (TDF) was investigated in 142 HIV+ patients exposed to the drug for longer than 12 months. No evidence of liver enzyme elevations were seen, even in 66 patients with chronic hepatitis C virus (HCV) co-infection. Given that TDF is an adenosine analogue, like didanosine, exposure to ribavirin might increase intracellular phosphorylated TDF metabolites, which could result in a higher risk of nephrotoxicity. Signs of tubular dysfunction in blood or urine were not recognized in 17 HCV-HIV co-infected patients exposed to TDF during interferon plus ribavirin therapy.

Background: Tenofovir (TDF) and didanosine (ddI) are both adenosine analogues with convenient posology, strong potency and a relatively high genetic barrier for resistance. The popularity of this combination, however, has been questioned due to concerns about pharmacokinetic interactions and increased risk of pancreatitis and hyperglycemia. Less information is available about other possible side effects., Patients and Methods: HIV-infected individuals who initiated a protease inhibitor-sparing regimen between September 2002 and June 2003 at five hospitals, and had at least one subsequent visit within the next 12 months, always with complete virus suppression, were retrospectively assessed. Only drug-naive individuals and patients who simplified a prior successful antiretroviral regimen were analysed., Results: Outcomes were analysed in 570 individuals according to treatment modality (98 drug-naive versus 472 simplified); the nucleoside analogue (NA) backbone (298 with TDF + ddI, 88 with ddI, 44 with TDF, and 140 with neither ddI nor TDF); and the third agent used (378 with non-nucleoside analogues versus 192 with NA). Significant CD4+ T-cell declines were seen in patients taking ddI + TDF with respect to all other NA combinations, including ddI or TDF separately. Patients exposed to high ddI doses or taking a third NA showed more pronounced CD4 declines. Plasma levels of ddI correlated with the extent of CD4+ T-cell loss., Conclusion: Patients receiving ddI + TDF-based combinations show CD4+ T-cell declines despite achieving complete virus suppression. This effect generally progresses with time. An imbalance in adenosine metabolites within CD4+ T lymphocytes may explain this phenomenon, which resembles the genetic purine nucleoside phosphorylase deficiency syndrome.

Background: Simplified highly active antiretroviral therapy (HAART) regimens are becoming widely used, particularly as a result of the side effects of and difficult compliance with protease inhibitor (PI) therapy. However, the long-term efficacy of HAART has not been properly assessed., Methods: We performed a prospective study of 110 patients infected with human immunodeficiency virus type 1 (HIV-1) with undetectable virus load who discontinued PI therapy and initiated therapy with nevirapine without changing nucleoside analogues. Reasons for switching were treatment simplification (45%), lipodystrophy (24%), renal problems (23%), and dyslipidemia (8%). HIV-1 load, CD4 cell count, and fasting biochemistry profiles were performed at the time of switching (baseline) and every 3-4 months thereafter. The aim of the study was to evaluate the long-term efficacy and safety of this combination., Results: Sixty-eight patients (61.8%) had a duration of follow-up of 3 years. The mean increase in the CD4 cell count after 3 years was 90 cells/microL (13.8% from baseline). Virus loads remained undetectable in all patients but 9 (8.2%). Triglyceride levels dramatically improved at 12 months (a 75% decrease; P<.02) and remained statistically significant over time (P<.04). The same occurred with serum cholesterol levels: there was an initial reduction of 25% (P<.02) and at the end of the follow-up period (P<.015). However, at the long-term evaluation, complete normalization of mean serum cholesterol and triglyceride levels could not be achieved. Sixteen patients (14.5%) had to stop therapy as a result of nevirapine-associated side effects., Conclusions: The switching of a PI to nevirapine is a safe and well-tolerated option for maintaining long-term virological suppression and immunological control. Three years after starting nevirapine therapy, rates of hypercholesterolemia and hypertriglyceridemia improved, although normal cholesterol and triglyceride values were not achieved.