Alcohol and marijuana may reduce drug levels of atazanavir and efavirenz
31 December 2009. Related: Conference reports, PK and drug interactions, ICAAC 49th San Fransisco 2009.
Simon Collins, HIV i-Base
Two small studies from the same research group looked at the association between substance use, including alcohol and marijuana, and levels of HIV drugs.
The first study reported that trough concentrations of atazanavir were inversely related to use of tobacco and marijuana in 32 substance using (SU) patients from four US sites compared to 35 non-using (non-SU) patients. [1]
Substance use (% of SU patients) followed NIDA criteria and included alcohol (41%), cocaine (19%), marijuana (38%), opioids (22%) and tobacco (91%). 43% of these patients used multiple substances.
During the study period, patients had to complete three clinic visits, for entry, trough and directly observed therapy (DOT), and take scheduled doses of atazanavir at the same time for 4 days before each visit.
Adherence assessment and counseling prior to plasma sampling and each scheduled clinic visit were performed and recorded.
Multiple linear regression models were used to determine factors associated with atazanavir concentrations, immunological and virologic responses while adjusting for covariates. Other demographics including race, gender, ethnicity and BMI were included in the analysis.
Significant reductions in ATV trough concentrations were associated with tobacco and marijuana use (p<0.05) but not with other substances. 36% and 50% of tobacco and marijuana users, respectively had ATV concentrations below the therapeutic range (p<0.05). However, no significant direct effects were linked to viral load or CD4 count.
Table 1. Substance use (SU) and atazanavir trough levels*
| SU | Non-SU | P | |
| Tobacco | 0.31 (0.12-0.79) | 0.96 (0.32-1.20) | 0.009 |
| Marijuana | 0.24 (0.05-0.80) | 0.59 (0.27-1.11) | 0.03 |
| Alcohol | 0.53 (0.13-0.91) | 0.56 (0.22-1.08) | 0.60 |
| Cocaine | 0.77 (0.05-1.39) | 0.54 (0.19-1.05) | 0.92 |
| Opioids | 0.32 (0.15-0.77) | 0.71 (0.19-1.10) | 0.22 |
* Median, ug/ml (IQR). For HTB, rounded to two decimal points.
The researchers concluded that the underlying mechanism may include enzyme induction, but that further studies were needed for this to be determined.
The second study looked at efavirenz metabolism in relation to the G516T single nucleoside polymorphisms (SNPs) in the CYP2B6 enzyme. Previous studies have demonstrated that GG > GT > TT polymorphisms inhibit efavirenz metabolism resulting in higher plasma concentrations, slower drug clearance, and sometimes increased toxicity.
Based on 516 genotypes, 37 patients (SU n=18; non-SU n=19) were categorised as extensive (GG, n=19), intermediate (GT, n=13), and slow (TT, n=5) metabolisers. These genotypes with were significantly associated with efavirenz trough concentrations (p=0.04). Significantly lower median (IQR) efavirenz concentrations were linked to tobacco use (1.76 ug/mL; (1.31-2.13) vs 2.29 ug/mL (1.88-4.01), p=0.04) and alcohol use (1.41 ug/mL (0.66-1.88) vs 2.25 ug/mL (1.76-2.48), p=0.02) in the extensive metaboliser group with lower CD4 counts and higher viral loads.
As with the atazanavir study, substance use had no significant relationship to antiviral responses.
References
- Fehintola FA et al. Tobacco and marijuana uses significantly decrease atazanavir (ATV) trough concentrations in HIV infected individuals. 49th ICAAC, 12-15 September 2009, San Francisco. Poster abstract H-231.
http://www.posters2view.com/icaac/view.php?nu=H-231 - Brazeau D et al. Effects of CYP2B6 single nucleotide polymorphisms (SNPs) and substance abuse on efavirenz (EFV) pharmacokinetics. 49th ICAAC, 12-15 September 2009, San Francisco. Poster abstract H-228.
http://www.posters2view.com/icaac/view.php?nu=H-228