HIV therapy based on efavirenz may less suitable for women taking combined oral contraception due to greater reductions in efavirenz levels and a higher frequency of hormonal contraception side effects, according to research
conducted in Thailand and published in the online edition of the Journal of Acquired Immune Deficiency
Results of the small study showed that only one-fifth
of women taking efavirenz and oral contraception had progesterone levels above
the target level and that 19% had efavirenz concentrations below the
therapeutic threshold. In contrast, women taking nevirapine were
protected against pregnancy and maintained therapeutic levels of the
“Our results suggest that co-administration
of COC [combined oral contraception]…with efavirenz is associated with risks
for contraceptive and efavirenz failures,” comment the investigators. “On the
other hand, the study results suggest that the use of such COC with nevirapine
resulted in more favorable ARV [antiretroviral] and progesterone levels.”
Contraception, including hormonal methods,
is widely promoted to women with HIV. However, little is known about
pharmacokinetic interactions between combined hormonal contraceptives and
common classes of antiretrovirals, such as non-nucleoside reverse transcriptase
inhibitors (NNRTIs). An interaction is
theoretically possible because both combined contraceptives and NNRTIs are
metabolished by the body in the same way.
Investigators in Thailand therefore
designed a prospective open-label study involving 34 women taking a combined
oral contraceptive formula of 0.150 mg desogestrel/0.030 mg ethinyl estradiol (Marvelon 150/30 tablets) and
antiretroviral therapy based on the NNRTIs efavirenz (Sustiva, also in Atripla)
or nevirapine (Viramune).
Recruitment occurred between August 2011
and April 2012 and participation in the study lasted for two months.
Between the first and third day of their
regular menstrual cycle, participants started to take one Marvelon tablet per day for 21 days, followed by seven days without
contraception; on day 29 day participants re-started Marvelon for another
All the women were taking stable
The target level for contraceptive effectiveness
was a progesterone level below 3.0ng/ml. Antiretroviral concentrations were
measured twelve hours after administration with and without combined oral
contraception. Target drug concentrations were above 3.1mg/l for nevirapine
and between 1.0-4.0mg/l for efavirenz.
Participants had a median age of 36 years.
All had normal blood pressure and body mass index. In most respects, the 18 women taking nevirapine and the 16 women taking efavirenz were well
matched in terms of baseline characteristics. However, those taking nevirapine
had higher systolic blood pressure, whereas those taking efavirenz had
higher ALT levels.
All the women maintained an undetectable
viral load throughout the study and reported 100% adherence to both their
contraceptive treatment and antiretroviral therapy.
Progesterone levels were below 1.0ng/ml
for all the women taking nevirapine. In the efavirenz group, twelve
individuals (75%) also had a progesterone level below 1.0ng/ml; four had
progesterone above 1.0ng/ml. including three individuals (19%) who had a
level above 3.0ng/ml.
“We caution the use of combined hormonal
contraceptives in HIV-positive women on efavirenz for pregnancy protection,”
write the authors.
Median nevirapine concentrations twelve
hours after administration without the combined oral contraception were 6.8mg/l, and these increased by an insignificant 17% to 7.2mg/l when taken with Marvelon. However, six women
experienced a fall in their nevirapine levels, including one woman where it
fell to 2.96mg/l, below the therapeutic threshold of 3.1mg/l.
The median concentration of efavirenz
without the contraceptive was 3.3mg/l. It fell by a significant 22% to 2.7mg/ml
with Marvelon. In three women
(19%) concentrations of the drug dropped below the target 1.0mg/l threshold.
“Efavirenz levels below the therapeutic
threshold of 1mg/l might be insufficient for effective viral suppression
possibly leading to therapeutic failure,” comment the researchers.
Significantly more women in the efavirenz
group reported side-effects attributed to the combined oral contraceptive than
women in the nevirapine group (56 vs 22%; p = 0.04).
“As efavirenz-based ARV is becoming the
preferred first-line option worldwide it is crucial to study in detail the
pharmacokinetic interaction between COC and NNRTI as well as its clinical
impact on contraceptive and HIV treatment effects in larger and more diverse
population,” conclude the investigators.