Background:  Perinatal exposure to dual nucleoside transcriptase inhibitors (NRTI) or highly active antiretroviral theraphy (HAART) significantly increased in the last years. Hyperlactatemia has been described in HIV-uninfected infants (SR) exposed to NRTI or HAART. Data on mitochondrial (mt) DNA content in this population are lacking.

Methods:  Plasma lactate and pH values were measured at birth (cord blood) and 6 months of age in 53 SR and 20 healthy controls. Among the 53 SR, 21 were exposed in utero to dual NRTI and 32 to HAART. The mean duration of NRTI and HAART exposure was 18.3 weeks (8.9) and 19.7 weeks (4.2). All SR were exposed to ZDV during delivery and the neonatal period (mean duration, 5.8 weeks). MtDNA content was measured by real-time PCR in platelet-free CD4⁺ cells isolated by magnetic separation in 7/21 NRTI, 10/32 HAART exposed and 10 healthy controls at birth and 6 months of age.

Results:  All SR were confirmed HIV-uninfected by 2 negative HIV PCR tests within 6 months of age. Mean gestational age, mean birth weight and mean cord blood pH were:  37.4 (0.1) weeks, 2818 (137.9) g and 7.39 (0.04) in NRTI exposed; 37.1 (0.1) weeks, 2695 (357.6) g, and 7.39 (0.03) in HAART-exposed and 39.2 (0.5) weeks, 3250 (220.3) g and 7.38 (0.03) in healthy controls. At birth, SR and healthy controls showed a comparable frequency of hyperlactatemia. Frequencies of lactate concentration >2.5 mmol/L were as follow: 10/21 (47%) in NRTI exposed, 14/32 (44%) in HAART exposed and 8/20 (40%) in healthy controls. Frequencies of lactate concentration >5 mmol/L were as follows: 3/21 (14%) in NRTI exposed, 5/32 (16%) in HAART exposed and 2/10 (20%) in healthy controls. At 6 months of age, all NRTI exposed, HAART exposed and HC showed lactate concentrations <2.5 mmol/L. At birth SR and healthy controls showed comparable value of mtDNA content in CD4⁺ cells. The median values of mtDNA content (copies/cell) were:  91.5 (range 57.2 to 220.0) in NRTI-exposed, 85.2 (range 22.8 to 356.0) in HAART exposed and 89.0 (range, 16.2 to 231.2) in healthy controls. Similar results were observed at 6 months of age. The median value of mtDNA content (copies/cell) were: 53.7 (range 31.7 to 278.5) in NRTI-exposed, 132.0 (range 29.7 to 316.0), and 98.0 (range 21.0 to 216.2).

Conclusions:  Transient hyperlactatemia occurs at comparable rates in healthy and antiretroviral exposed newborns. At birth and 6 months of age, antiretroviral exposed newborn did not show alterations in mtDNA content in CD4⁺ cells. Our data do not support a mitochondrial damage as a consequence of antiretroviral exposure. 

Keywords: mitochondrial damage; antiretroviral therapy; HIV-exposed uninfected children