Background: Diarrhea is a common adverse effect of protease inhibitor (PI) therapy. We previously reported that dietary lactose exacerbates nelfinavir‑associated diarrhea (NFVAD) and a lactose free diet ameliorates it. In this study we tested whether NFV exposure alters lactase activity in treated patients.

Methods: We used the Breath Hydrogen Test (BHT) to quantify lactase activity in 11 HIV-infected adult patients before and during NFV treatment. Subjects were excluded if they had taken antibiotics or other PIs in the month preceding the BHT or had any comorbid conditions known to cause diarrhea. Subjects received a low fiber and lactose free diet the day before the BHT and fasted overnight. The BHT was administered immediately prior to and at least 30 days after starting NFV in combination with nucleoside analogs. All subjects were questioned about symptoms suggestive of lactose intolerance during the lactose challenge. Exhaled breath samples were collected via a nasal prong before and then at 30 min intervals for 3 hours after the ingestion of 50 grams of lactose diluted in 250 mL of water. Breath samples were analyzed for H₂ concentration on a Quintron MicrolyzerÔ and results were expressed as parts per million (ppm/hr) and represented as the 3-hour area-under-the-concentration-time-curve (AUC). Lactase deficiency was defined as a rise in exhaled H₂ concentration of >10 ppm/hr above the baseline beyond the first 30 minutes in combination with gastrointestinal symptoms associated with the lactose challenge.

Results: All 11 patients were African American (7 females and 4 males, ages 23 to 50 yr). Following at least 30 days of NFV, the mean H₂ AUC post NFV treatment for the 11 subjects [494 ppm/hr (range 226-853)] was not significantly different from the baseline [412 ppm/hr (range 269-517)] (p<0.2; Rank Sum Test).

Conclusions: Mean BHT was not significantly altered by NFV exposure for >30 days. In addition, no subjects experienced symptoms of lactose intolerance, including bloating or diarrhea, with lactose challenge. These findings are consistent with in vitro data indicating that lactase activity in vitro is not affected by NFV exposure. These results suggest that NFVAD is unlikely to be caused by altered lactase activity, and that lactose intolerance is not likely to be induced by PIs.

Keywords: Diarrhea; lactase; nelfinavir