Four days of nevirapine plus a month of 2 NRTIs appears to be ‘safe’ PEP strategy

Doctors from Strasbourg, France, argue that four days of nevirapine taken with a month of dual nucleoside analogue (NRTIs) as post-exposure prophylaxis (PEP) is clinically and biologically safe and effective, according to a brief report of a retrospective review published in the December 1st issue of the Journal of Acquired Immune Deficiency Syndrome (JAIDS).

The non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine has recently fallen out of favour for use in PEP for both potential occupational and non-occupational HIV exposure due to concerns about nevirapine’s short- and mid-term skin and liver toxicity in individuals with high CD4 cell counts.

A study published in JAIDS last February found that HIV-uninfected people had a higher risk of side-effects when exposed to nevirapine, possibly due to immune system factors, concluding that “non-HIV infected individuals should not receive PEP or other prophylaxis regimens that include multiple doses of nevirapine."

Nevirapine-containing PEP has been available at Hôpitaux Universitaires Strasbourg since January 2000, but instead of a month of triple therapy, PEP recipients have been prescribed four days of nevirapine (200mg daily) plus Combivir (AZT, 3TC) or stavudine (d4T) and lamivudine (3TC), where resistance to AZT (zidovudine) was suspected. Doctors there hypothesised that four days of nevirapine, which due to its long half-life would provide an estimated ten days of anti-HIV activity, would result in the best balance of efficacy to toxicity. They also suspected that this combination would be easier to take than PI-based PEP, leading to better adherence.

A retrospective review of their HIV PEP charts evaluated the clinical and biological tolerability of nevirapine-containing PEP. However, there was no adherence questionnaire in this review, and follow-up to six months was less than complete: fewer than 20% of individuals exposed non-occupationally and 35% of those exposed occupationally had six month follow-up data available, so that the effectiveness of this PEP regimen could not be strictly measured.

In total, 120 individuals received this PEP regimen; 44 exposures were occupational (25 of which were needle-stick injuries) and 76 were non-occupational (the vast majority of which were sexual, due to either rape-associated unprotected vaginal or anal intercourse, or condom breakage). The average time to the start of PEP was 10.5 and 20 hours in occupational and non-occupational exposure, respectively.

Of the 120 individuals, 100 (83.3%) completed at least the four-day course of nevirapine; 15 of the 20 who discontinued PEP early did so after discovering that the source was, in fact, HIV-negative. Nevirapine was stopped in two patients for clinical side-effects that were presumed to be linked to the medication; one self-reported a skin rash on day 2, and another had digestive intolerance after three days. The doctors were unable to ascertain the exact duration of PEP in the other three patients.

There was a high frequency of side effects reported (68 out of 120, or 57%), although most were considered to be mild or moderate. These included: nausea (n=35), weakness (n=30), abdominal pain (n=20), headache (n=10) and diarrhoea (n=6). A further ten individuals discontined PEP after four days due to intolerance to one or both of the NRTIs.

Only 104 patients had liver function tests (ALT) available. Five of the 104 (4.8%) experienced moderate elevations in ALT (ranging from 1.4 to 2.4 ULN) between two days and a month after taking PEP. Normalisation occurred in the two that were not lost to follow-up. Two patients had ALT levels two-three times the upper limit of normal (ULN) prior to starting PEP; one had an unspecified increase in ALT six months later and the other patient was lost to follow-up.

No HIV or HCV seroconversions were seen during follow-up, although only 38% and 48% of individuals were followed-up three months after non-occupational and occupational exposure, respectively. The percentage followed-up to six months was 20% and 35% of those exposed non-occupationally and occupationally, respectively.

The authors conclude that “because nevirapine-induced hepatotoxicity clearly increases over treatment time, we believe that four-day course of 200mg of nevirapine once a day is safe in this PEP setting, even in individuals who have a low follow-up rate, because only four nevirapine pills are given to the patient.”