Background:  Structured HAART interruptions improve or even revert some ART-associated toxicities, such as dyslipemia. However, data are scarce regarding benefits of this strategy on lipodystrophy and other mitochondria-related clinical events. The objective of the current study is to assess whether prolonged HAART interruptions improve mitochondrial (mt) DNA levels.

Methods:  This is a mitochondrial substudy of the TIBET Study, a multicenter, prospective, comparative-controlled trial in which patients with viral suppression during HAART were assigned to continue or interrupt HAART. Quantification of mtDNA and nuclear (n) DNA amount were determined by performing real time polymerase Caín reaction (PCR) at baseline and weeks 96 and 144 in those 16 patients from the TIBET Study who achieved week 96 without therapy (13 of the 16 remained without therapy until week 144) (off-therapy group) and in 20 patients who continued HAART (16 of 20 with follow-up until week 144) (on-therapy group). Mean (±SD) mtDNA/nDNA ratio was used for comparisons between groups (t-test).

Results:  Both groups presented a significant and progressive decrease in mtDNA/nDNA ratio without differences between them (p = 0.379 at week 96; p = 0.935 at week 144). The off-therapy group showed a decline in ratio from 1±0 at baseline to 0.81±0.31 at week 96 (p = 0.027) and to 0.67±0.42 at week 144 (p = 0.025). In the on-therapy group, the ratio decreased from 1±0 at baseline to 0.82±0.36 at week 96 (p = 0.037) and to 0.70±0.17 at week 144 (p = 0.010). The mean percentage of change in ratio at week 144 from baseline was –33.5% and –29.9% in the off-therapy and on-therapy groups, respectively (p = 0.935 between groups).

Conclusions:  Surprisingly, mtDNA did not improve as expected in patients who discontinued ART for a long period. The fact that patients without therapy presented maintained detectable viremia throughout the follow-up could explain the lack of benefit of treatment interruption in terms of mitochondrial toxicity, since the association between HIV and mitochondrial toxicity has already been described. Another possible explanation for our results could be an irreversible mitochondrial dysfunction.