Several factors are known or suspected to increase the likelihood that HIV-positive people taking nucleoside reverse transcriptase inhibitors (NRTIs) will develop mitochondrial toxicity:

• Simultaneous use of multiple mitotoxic agents.
• Longer use of NRTIs.
• More advanced HIV disease.
• Low CD4 cell count.
• Older age.
• Obesity or high body mass index.
• Pre-existing liver impairment.
• Co-existing medical conditions such as diabetes or hepatitis C.

It is clear that not everyone taking mitotoxic NRTIs develops hyperlactataemia or other conditions attributed to mitochondrial toxicity. However, data from different studies are contradictory regarding who is at risk.

Whilst some studies have found higher rates of mitochondrial damage and associated symptoms in people with lower CD4 cell counts, others have not seen such a relationship^[1][2]. The same is true for duration of NRTI use.

The United States Food and Drug Administration’s reporting programme found that most of the HIV-positive patients who died due to lactic acidosis were women, some of whom were pregnant. Although a majority of studies suggest that women are more prone to mitochondrial toxicity and its associated conditions, other studies have found higher rates in men, and still others saw no difference^[3].