TABLE 3C.
Impact of HIV on CYP substrates, explained totally or partially by modulation of CYP activity.
| Inflammation characterized by | Victim drugs (CYP concerned) | Number of subjects | Potential effect of interaction | References and design |
|---|---|---|---|---|
| AIDS patients vs control | clindamycin (CYP3A) | 16 = AIDS | - clearance values normalized to subject body weight were 0.27 ± 0.06 L/h/kg for the healthy volunteers and 0.21 ± 0.06 L/h/kg for the AIDS patients (p = 0.014) | Breimer et al. (1975) |
| 16 = healthy volunteers | - ADR following administrations (same dose) were observed in eight patients with AIDS | Case-control study | ||
| HIV-infected patients vs control | midazolam (CYP3A), dextromethorphan (CYP2D6) and caffeine (CYP1A2) | 17 = HIV-infected | - midazolam clearance was significantly lower in HIV-infected patient compared with healthy volunteers (CI95% = 0.68–0.92) and a significant relationship was found with TNF-α (r = −0.66, p = 0.008) | Imai et al. (2011) |
| 17 = | - urinary dextrometorphan MR was significantly higher in HIV-infected patients than in healthy volunteers (CI95% = 2.36–42.48) and a trend was observed for an association with the increase in TNF-α concentration (r = 0.49, p = 0.06) | Case-control study | ||
| uninfected | - caffeine metabolism was no significantly different in HIV-infected subjects compared to non-smokers healthy volunteers (controlled for smoking status) (CI95% = 0.83–3.11) | |||
| HIV-infected patients vs control | midazolam (CYP3A) and | 30 = HIV-infected | - CYP3A4 activity in HIV infected patients was approximately 50% of the activity in healthy volunteers but it was mainly attributable to a lower intestinal CYP3A4 activity, while hepatic CYP3A was not different | Gatti et al. (1993) |
| dextromethorphan (CYP2D6) | 12 = healthy volunteers | - CYP2D6 activity was essentially comparable | Case-control study | |
| HIV-positive patients | dextromethorphan (CYP2D6) | 61 | - 2 of the 59 patients with an NM genotype expressed a PM phenotype and 4 NM genotype patients were less extensive dextrometorphan metabolizers than any of the patients receiving medication known to inhibit CYP2D6 | Jones et al. (2010) |
| Cohort study | ||||
| HIV-1 infected patients vs control | darunavir (CYP3A) | Unknown, information obtained from Summary of Product Characteristics (SmPC) | - exposure to darunavir was higher in HIV-1 infected patients | Jetter et al. (2010) |
| - explained by the higher concentrations of α1-glycoprotrein in HIV-1 infected patients, resulting in higher darunavir binding to plasma AAG and, therefore, higher plasma concentrations | Case-control study | |||
| HIV-infected patients vs healthy volunteers | saquinavir (CYP3A) | 33 = HIV-infected | - co-administration of ketoconazole increased saquinavir AUC by 190 and 69% in healthy volunteers and HIV-infected patients, respectively while co-administration of rifampicin decreased saquinavir area under the curve by 70 and 46% | European medicines agency |
| Case-control study | ||||
| 12 and 14 = control | ||||
| HIV-infected patients vs healthy controls | atazanavir and atazanavir with ritonavir (CYP3A) | Unknown, information obtained from SmPC | - mean AUC of atazanavir and atazanavir with ritonavir were 29′303 and 61′435 ng*h/mL respectively in healthy volunteers, vs. 22′262 and 53′761 ng*h/ml, respectively in HIV-infected patients | Grub et al. (2001) |
| Case-control study | ||||
| HIV-infected patients vs healthy controls | lopinavir with ritonavir (CYP3A) | Unknown, information obtained from SmPC | - no substantial differences observed between the two groups | Packageinserts |
| Case-control study | ||||
| HIV-infected patients vs healthy controls | atazanavir (CYP3A) | 10 = HIV-infected | - mean atazanavir AUC in HIV-infected patients was 14′187 ng*h/ml compared with 33′097 ng*h/ml in healthy volunteers | Le Tiec et al. (2005) |
| 36 = healthy volunteers | - after 14 and 20 days of atazanavir in HIV patients and healthy volunteers, respectively, AUC were 46′073 and 57′039 ng*h/ml | Case-control study | ||
| Patients with different stage of HIV infection vs control | caffeine (CYP1A2) | 29 = AIDS | - metabolic status was not change in HIV asymptomatic patients but changed in AIDS patients (with acute illnesses or stable) | Venuto et al. (2018) |
| 29 = AIDS-stable | Case-control study | |||
| 18 = HIV-infected | ||||
| 29 = control | ||||
| HIV infected patients | atazanavir (CYP3A) | 107 = HIV-1 infected | - apparent oral clearance was not significantly correlated with inflammatory biomarkers | Lee et al. (1993) |
| Cohort study |