Table 2.
Treatment | Gender difference | Nature of difference in women versus men | Clinical implications |
---|---|---|---|
Protease inhibitors | |||
Ritonavir (SCG formulation) | Yes | 31% ↑ median AUC0–12 h (p=0.026) ↑ median Cmax (p=0.032) 24% ↓ CL/F (p=0.026) |
Gender differences in RTV concentrations might have a significant influence in settings where RTV is used to boost other protease inhibitors or in the magnitude and perhaps clinical significance of RTV drug-drug interactions [29] |
Ritonavir (Tablet) | Yes | 35% ↑ median AUC0–12 h (p=0.012) ↑ median Cmax (p=0.006) 26% ↓ CL/F (p=0.012) |
|
Indinavir/r | Yes | 30% ↓ clearance (p<0.05) | Initial dosage should be decided according to ritonavir intake and gender, prior to plasma concentration measurements [30] |
Saquinavir/r | Yes | 25% ↑ AUC0–12 h (p=0.004) 3-fold ↑ Cmin (p<0.001) ↑ Cmax (p<0.05) ↑ Inhibitory quotient |
A greater proportion of females than males had HIV RNA values ≤500 at week 16 of the study period [31–33] |
Lopinavir/r | No | None | None [29] |
Saquinavir | No | None | None [34] |
Indinavir | No | None | None [35] |
Atazanavir/r | Minimal | None | None [36] |
Fosamprenavir | Minimal | None | None [37] |
Fosamprenavir/r | Minimal | None | None [37] |
NRTIs and NNRTIs | |||
Nevirapine | Yes | 44% ↑ Cmax (p=0.042) 1.5-fold ↑ ΔC (p=0.02) 0-22% ↑ random concentration 25% ↓ weight-adjusted clearance |
Evidence suggests particular sensitivity of females to nevirapine toxicity, including rash and hepatotoxicity [38–40] |
Efavirenz | Yes | ↑ mean plasma concentration (p<0.001) 25% ↓ AUC0–24h (p=0.05) Slight ↑ clearance (L/h) |
Physicians should be aware of a higher risk for drug-induced toxicity in females [23] |
Delavirdine | Yes | ↓ mean intrinsic clearance (p=0.05) | None [41] |
Etravirine | No | None | None [42] |
Rilpivarine | No | None | None [26] |
Lamivudine | Yes | 1.6-fold ↑ in intracellular nucleoside triphosphates (p=0.002) | Physicians should be aware of a higher risk for drug-induced toxicity in females [43] |
Zidovudine | Yes | 2.3-fold ↑ in intracellular nucleoside triphosphates (p=0.002) | |
Other agents | |||
Enfuvirtide | Yes | 35% ↓ clearance | Changes in exposure do not appear to affect efficacy or safety [41] |
Maraviroc | ND | ND | ND |
Raltegravir | No | None | None [44] |
Elvitegravir/Cobisistat | ND | ND | ND |
SGC=soft gel capsules; CL/F=apparent oral clearance; AUC=area under the curve; Cmin=minimum plasma concentration; Cmax=maximum plasma concentration; ΔC=difference between maximum and minimum concentrations (Cmax−Cmin); Ctrough=plasma concentration just before the next dose; ND=no data available.