To investigate the change regularity of peripheral blood mononuclear cell (PBMC) mtDNA (mitochondrial deoxyribonucleic acid) content and its association with HIV-LD (human immunodeficiency virus-related lipodystrophy) in HAART (highly active antiretroviral therapy).At baseline, Months 6 and 24 of therapy, the cryopreserved PBMC were collected from 33 patients on a regular follow-up at our clinic. Among them, 17 had HIV-LD. Then total DNA was extracted and mtDNA content quantified by real-time PCR (polymerase chain reaction).The HIV/AIDS patients had a lower content of PBMC mtDNA (2(-ΔΔCt)) than the healthy controls at baseline (9.578 vs 17.195, P < 0.01). The mtDNA content was lower in the HIV-LD group than that in the no LD (NLD) group at each time point of therapy (13.619 vs 5.775, 6.360 vs 1.387, 7.170 vs 1.266, all P < 0.05). In the HIV-LD group, the half- and 2-year PBMC mtDNA content was markedly lower than those at baseline (both P < 0.05). And the change of mtDNA content (within half a year) was earlier than the onset of clinical HIV-LD at one year later. In the NLD group, the PBMC mtDNA content have an insignificant change after therapy. The mtDNA content decreased significantly in stavudine (d4T)-containing regimen group after treatment (P < 0.01), but showed no significant change in zidovudine (AZT)-containing regimen group after therapy.The decreased content of PBMC mtDNA after HIV infection and during HAART therapy is associated with HIV-LD. Nucleoside reverse transcriptase inhibitor, especially d4T, plays an important role in the progression of HIV-LD.