- Less likely with 3TC, FTC, ABC, TAF, and TDF
- See the Risk Factors and Prevention/Monitoring columns for information regarding the toxicity of propylene glycol when LPV/r oral solution is used in neonates.
- Generally after years of exposure
Lactic Acidosis May Also Present with Insidious Onset of a Combination of Signs and Symptoms:
- Lactic acidosis may be clinically asymptomatic.
Note: Patients may present with acute multi-organ failure (e.g., fulminant hepatic failure, pancreatic failure, respiratory failure).
- Generalized fatigue, weakness, and myalgias
- Vague abdominal pain, weight loss, unexplained nausea, or vomiting
- Peripheral neuropathy
|Lactic acidosis is associated with use of ddI and d4T. Cases are rare now that these NRTIs are no longer recommended.
3TC, FTC, ABC, TAF, and TDF are less likely to induce clinically significant mitochondrial dysfunction than ZDV.
Preterm Infants or Any Neonates Who Have Not Attained a Post-Menstrual Age of 42 Weeks and a Postnatal Age of ≥14 Days:
- Female sex
- High BMI
- Chronic HCV infection
- African-American race
- Coadministration of TDF with metformin
- Overdose of propylene glycol
- CD4 count <350 cells/mm3
- Acquired riboflavin or thiamine deficiency
- Possibly pregnancy
- Exposure to propylene glycol, which is used as a diluent in LPV/r oral solution. A diminished ability to metabolize propylene glycol may lead to accumulation, increasing the risk of adverse events.
- Due to the presence of propylene glycol as a diluent, LPV/r oral solution should not be used in preterm neonates or any neonate who has not attained a postmenstrual age of 42 weeks and a postnatal age of ≥14 days.
- Monitor for clinical manifestations of lactic acidosis and promptly adjust therapy.
Patients with Clinical Signs or Symptoms Consistent with Lactic Acidosis:
- Measurement of serum lactate is not recommended.
- Obtain blood lactate level.a
- Additional diagnostic evaluations should include serum bicarbonate, anion gap, and/or arterial blood gas; amylase and lipase; serum albumin; and hepatic transaminases.
|For Patients with Lactate 2.1–5.0 mmol/L (Confirmed with a Second Test):
For Patients with Lactate >5.0 mmol/L (Confirmed With a Second Test)b or >10.0 mmol/L (Any One Test):
- Consider discontinuing all ARV drugs temporarily while conducting additional diagnostic workup.
Anecdotal (Unproven) Supportive Therapies:
- Discontinue all ARV drugs.
- Provide supportive therapy (e.g., IV fluids; some patients may require sedation and respiratory support to reduce oxygen demand and ensure adequate oxygenation of tissues).
Following the resolution of clinical and laboratory abnormalities, resume therapy, either with an NRTI-sparing regimen or a revised NRTI-containing regimen. Institute a revised NRTI-containing regimen with caution, using NRTIs that are less likely to induce mitochondrial dysfunction (ABC, TAF, TDF, FTC or 3TC). Lactate should be monitored monthly for ≥3 months.
- Administer bicarbonate infusions, THAM, high doses of thiamine and riboflavin, oral antioxidants (e.g., L-carnitine, co-enzyme Q10, vitamin C)