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. 2013 Oct 1;16(1):18509. doi: 10.7448/IAS.16.1.18509

Table 2.

Gender differences in antiretroviral pharmacokinetic parameters

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 [3133]
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 [3840]
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.