Elvitegravir

Additional information

Antiretrovirals for treatment of HIV are always given as a combination of at least three medicines. Cobicistat is used to boost the effect of other antiretroviral drugs. As studies on HIV patients always include patients receiving combination therapy it is difficult to know which of the studied medicines that cause changes in effect and/or adverse events.

Pharmacokinetics and dosing

In the FDA Summary review it is stated that women had higher elvitegravir exposures than men, but also that 54% of women compared to 41% of men had a documented undetectable elvitegravir blood levels suggesting poorer adherence to the treatment regimen byin women [1]. In a population pharmacokinetic analysis of cobicistat or ritonavir in combination elvitegravir (in all 1046 men, 410 women) patients’ sex did not affect pharmacokinetic variables [2].

Effects

Both women and men have been included in the pivotal studies [1]. In the FDA Summary review the findings of subgroup analyses suggest that women, non-white subjects, and patients in non-US regions had lower treatment response to elvitegravir compared to raltegravir [1]. However, there are several uncertainties regarding this finding; it only concerns secondary outcomes, it was not consistent over time, no correction was made for multiple testing. Thus this finding may be due to chance [1].

Adverse effects

Safety and tolerability were evaluated in a European HIV cohort with antiretroviral treatment (958 men, 336 women). Women had a higher risk of treatment discontinuation than men but no increased risk of virological failure. Compared to men, women had less diarrhoea and severe dyslipidaemia but more lipodystrophy [3]. Similarly, in a Spanish retrospective observational study of dolutegravir and elvitegravir/cobicistat treatment in HIV patients (414 men, 128 women) women in both treatment groups were more prone to discontinuation due to adverse events than men [4].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).