Abstract 624 - Incidence and Outcome of Hyperlactatemia Associated with Clinical Manifestations in HIV-Infected Adults Receiving NRTI-Containing Regimens.

624 Incidence and Outcome of Hyperlactatemia Associated with Clinical Manifestations in HIV-Infected Adults Receiving NRTI-Containing Regimens.

J. T. Lonergan*, D. Havlir, E. Barber, and W. C. Mathews.
Univ. of California San Diego, La Jolla.

Background:We reported a case series suggesting there is a milder, and perhaps earlier, form of the NRTI-associated lactic acidosis/hepatic steatosis syndrome occurring at a higher incidence rate (IR) than previously estimated for the severe form. It is unknown whether the IR of these syndromes varies with different NRTI combinations and whether affected patients can be safely rechallenged with alternative ones.

Methods:The case definition used for this study is an adult receiving NRTI-containing regimens with reproducible hyperlactatemia coupled with either GI symptoms or an unexplained elevated ALT or both. We calculated the IR of developing this syndrome by NRTI components of antiretroviral regimens. Relative risks (RR) of developing the syndrome for each regimen compared with ZDV/3TC-containing regimens were estimated.

Results:Between 7/98 and 5/00 we identified 33 patients who met the case definition criteria. The overall IR of the syndrome among 1611 patients receiving any NRTI-containing regimen during the study period was 14.5 (95% CI: 10.0—20.3) cases/1000 person-years (c/py). The IR for any d4T-containing regimen was 25.6 (95% CI: 17.4—36.4) c/py compared with 1.9 (95% CI: 0.2—6.6) c/py for NRTI-containing regimens without d4T. The IR of the syndrome ranged from 1.6 (95% CI: 0.04—9.0) c/py for ZDV/3TC to 238.1 (95% CI: 77.3—555.6) c/py for d4T/ddI/3TC. Compared with regimens that include ZDV/3TC, the RR of the syndrome was 11.6 (95% CI, 1.5—87.9; P = 0.018) for regimens with d4T/3TC, 15.0 (95% CI, 1.4—165.0; P = 0.027) for regimens with d4T/ABC, 36.3 (95% CI, 4.6—283.7; P = 0.001) for regimens with d4T/ddI, and 147.9 (95% CI, 17.3—1265.6; P < 0.0001) for regimens with d4T/ddI/3TC. To date 0/17 patients re-challenged with>2 NRTIs for >6 months have had a recurrence of the syndrome. In 16/17 patients, d4T was replaced by either ABC (n = 10), ZDV (2) or both ABC/ ZDV (4) in the new regimen.

Conclusions:There is a higher IR of hyperlactatemia with clinical manifestations in patients receiving d4T-containing regimens compared with NRTI-containing regimens without d4T. The greatest risk of developing this syndrome occurs when ddI or ddI/3TC is paired with d4T. It appears safe to rechallenge affected patients previously on d4T with either ABC or ZDV or both.