AEGiS-14IAC: Preserved mitochondrial/nuclear (mt/n) DNA ratios in peripheral blood cells from HIV-infected individuals on stavudine-sparing regimens.

14th International AIDS Conference


Barcelona, Spain - July 7-12, 2002

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Preserved mitochondrial/nuclear (mt/n) DNA ratios in peripheral blood cells from HIV-infected individuals on stavudine-sparing regimens.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no.. WeOrB1304)

Cote HC, Yip B, Chan JW, Brumme ZL, Hogg RS, Harrigan PR, O'Shaughnessy MV, Montaner J
B.C. Centre for Excellence in HIV/AIDS, St.Paul's Hospital, Vancouver, Canada

BACKGROUND: Stavudine (d4T) use has been associated with mitochondrial toxicity and hyperlactatemia. This has been correlated with depletion of peripheral blood cell mtDNA (Cote et al, NEJM, 2002). We investigate here the relative mt/nDNA ratios in relation to various selected antiretroviral drug regimens in a populational setting.

METHODS: We conducted a cross-sectional study on a non-random sample of participants within the BC CFE Drug Treatment Program. Eligible patients had continuously received saquinavir plus ritonavir with either nevirapine (N=20), lamivudine (N=15), stavudine (d4T)(N=53) or lamivudine + d4T (N=69), for 4 to 30 months. Participants were included if a buffycoat sample collected between Aug 1998-Sept 2001 was available for testing. The mt/nDNA ratio was measured using real-time PCR on the last sample collected during the observation period.

RESULTS: d4T-sparing regimens were associated with a higher median mt/nDNA ratio than d4T-containing regimens (1.16 vs 0.95, P=0.016). The mt/nDNA ratios were skewed toward lower values for the d4T-containing regimens but normally distributed for the d4T-sparing ones. Of note, patients received d4T-containing regimens for a shorter median time than those on d4T-sparing ones (13 vs 25 months, P=0.002).

CONCLUSION: mtDNA/nDNA ratios were statistically significantly lower in d4T-containing regimens than in selected d4T-sparing regimens in a populational setting. These results represent a conservative estimate of the magnitude of the effect of stavudine containing regimens on mt/nDNA ratios, due to survivor bias effect. Further work is currently underway to evaluate other antiretroviral regimens such as those containing didanosine, zalcitabine, or hydrea which may further enhance the effect here described.

Keywords: AEGIS, Stavudine, HIV Infections, Didanosine, Lamivudine, Nevirapine, DNA, Zalcitabine, DNA, Mitochondrial, HIV Seropositivity, Mitochondria, Blood Cells, Cross-Sectional Studies, Human, BloodKWDaegis,stavudine,hivinfections,didanosine,lamivudine,nevirapine,dna,zalcitabine,dna,mitochondrial,hivseropositivity,mitochondria,bloodcells,cross-sectionalstudies,human,blood

020707
WeOrB1304

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