Powderly W, Mondou E, Shaw A, Wakeford C, Adda N, Quinn JB, Rousseau F; IAS Conference on HIV Pathogenesis and Treatment (2nd : 2003 : Paris, France).

Antivir Ther. 2003; 8 (Suppl.1): abstract no. 737.

Washington University School of Medicine, St. Louis, MO, USA

BACKGROUND: Mitochondrial toxicity has been implicated in the development of symptomatic hyperlactataemia (SH) resulting from long-term use of NRTIs. FTC is a new once-daily NRTI with potent activity against HIV and HBV. In vitro, FTC is very selective; it is a poor substrate for mitochondrial DNA polymerase and is not cyto-toxic in HepG2 cells. METHODS: The incidence of SH from all studies of FTC-treated HIV+ and HBV+ patients was evaluated. Cases were identified in the adverse event database from spontaneous investigator reports of lactataemia/lactic acidosis associated with laboratory evidence of increased blood lactate above the normal range. Generally, the clinical manifestations included 31 of the following: nausea, abdominal pain, abdominal bloating, anorexia, fatigue or elevated alanine aminotransferase. The incidence of SH per 1000 person-years of exposure (PYE) to FTC was summarized by background regimen. RESULTS: 1994 HIV+ and 233 HBV+ patients were evaluated, with a total of 3013 PYE. Overall there were 22 cases of SH (7.3 cases/1000 PYE). There were no cases of SH among HBV+ patients treated for 259 PYE with FTC monotherapy, nor for HIV+ patients given FTC+ddI or FTC+AZT during 1220 PYE. Among HIV+ patients treated with FTC+d4T plus a NNRTI/PI, 10 cases (7.6 cases/1000 PYE) were observed. Twelve cases of SH (57.2/1000 PYE) were observed with the triple NRTI regimen of FTC+d4T+ABC. Within one double-blind comparative trial of HIV+ patients used in the above analysis, the incidence of SH was significantly higher in the d4T+ddI+EFV control arm (7/285; 2.5%) compared to the FTC+ddI+EFV arm (0/286) (P=0.007). CONCLUSIONS: SH has been observed with a low frequency with FTC and compares favourably with previously reported findings from other cohorts. Cases were observed only with the concomitant use of d4T. Consistent with previously published findings SH was observed more frequently with triple NRTIs than with regimens containing dual NRTIs.

Publication Types:

• Meeting Abstracts

Keywords:

• Acidosis, Lactic
• Acquired Immunodeficiency Syndrome
• Anti-HIV Agents
• Deoxycytidine
• Didanosine
• HIV
• HIV Infections
• HIV Seropositivity
• Humans
• In Vitro
• Lactic Acid
• Stavudine
• emtricitabine
• epidemiology

Other ID:

• GWAIDS0023392

UI: 102263016

From Meeting Abstracts