Background:  Increasing numbers of pregnant HIV⁺ women are receiving combination ART regimens for prevention of mother-to-child virus transmission or for treatment of the infection itself. Several studies have demonstrated that nucleoside reverse transcriptase inhibitors (NRTI) induce mitochondrial toxicity by several mechanisms, including depletion of mtDNA, whose levels are considered a marker of NRTI toxicity. By the quantification of mtDNA levels, we studied the role of mitochondrial toxicity in HIV⁺ women during pregnancy and the possible correlation with antiretroviral regimen, viro-immunological and metabolic parameters.

Methods:  HIV⁺ women were enrolled in the framework of the Italian Prospective Cohort Trial on Efficacy and Toxicity of Antiretroviral in Pregnancy (TARGET study). We analyzed 36 patients (mean age 32.6 years; 55.5% Caucasian, 36.1% African American, 2.8% Hispanic, and 5.6% other), that were in A1 CDC class (25.0%), A2 (41.7%), A3 (25.0%), and C2 (8.3%). During pregnancy, 25 patients were treated with lamivudine (3TC), 23 with zidovudine (AZT), 9 with combivir (AZT+3TC), and 4 with abacavir (ABC); 2 received didanosine (ddI), 1 stavudine (d4T), 16 assumed nevirapine (NVP), 8 nelfinavir (NFV), 4 lopinavir/ritonavir (LPV/r), and 4 tenofovir (TDF). Median time of treatment during pregnancy was 164 days. At the third, sixth, and ninth month of pregnancy we collected data on:  CD4 count, plasma HIV RNA, total and HDL-cholesterol, fasting glucose, and triglycerides. By real-time polymerase chain reaction (RT-PCR) (mtDNA qPCR), we quantified mtDNA copies per cell in subcutaneous fat samples collected during delivery. Statistical analysis was performed using Prism 3.03.

Results:  The mean of mtDNA copies per cell were 452±198 (mean±SD, range 178 to 922). Such value is similar to that found in subcutaneous fat from 10 age- and sex-matched healthy subjects (378±229). We found no association between mtDNA and CD4 count during pregnancy, HIV RNA, use of protease inhibitor (PI) or NNRTI in association with NRTI, total and HDL-cholesterol, fasting glucose, and triglycerides. No correlation was found between therapy length and exposure to drugs. During pregnancy, total and HDL cholesterol and triglycerides increased significantly, while fasting glucose remained constant; no association with mtDNA levels was observed.

Conclusions:  The therapy did not cause changes in adipose tissue mtDNA content, suggesting that treatment is apparently devoid of relevant mitochondrial toxicity.