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Session 22
Oral Abstracts Clinical Pharmacology: New Agents, Interactions, and Predictors of Virologic Response Thursday, 10 am - 12:30 pm Presentation Time: 11:15 am Ballroom A |
Background: Few data are available on the interaction of
progesterone-based contraceptives and ART, especially protease inhibitors (PI) and
non-nucleoside reverse transcriptase inhibitors (NNRTI). Millions of women
worldwide use DMPA (Depo-provera®) and interactions with ART could lead to
changes in efficacy or toxicity of either drug.
Methods: We prospectively determined the effect of DMPA
on the pharmacokinetics of nelfinavir (NFV), efavirenz (EFV), and nevirapine
(NVP) comparing ART AUC (0 to 12 h) at baseline and after 4 weeks of DMPA among
HIV-infected subjects (Wilcoxon signed-rank test). Safety and toxicity of DMPA
and ovulation suppression (using progesterone levels of < 5ng/mL by HPLC)
were assessed during the 12-week study with subjects on the PI and NNRTI
regimens compared to those on NRTI only or no ART (see the table below).
Subjects had not received DMPA within 180 days, any other hormones within 30
days, and had not taken both PI and NNRTI with their NRTI.
Results: We enrolled 65 evaluable women who were taking
NFV (n = 20), EFV (n = 15), and NVP (n = 14), or NRTI only or no ART (n = 16).
At entry, 55% of subjects were black, 21% Hispanic, and 18% white; median age
35; 24% had ever used injection drugs; median CD4 703 and median log10
HIV RNA 2.17, with 26% having HIV RNA < 50 copies; median weight was 156 lb;
all had negative pregnancy tests. No women appeared to ovulate during the study
and there were no pregnancies. DMPA was well tolerated with no grade 3 or 4
treatment related toxicities. Possibly treatment related grade 1 or 2
toxicities occurred in 17 (26%) of 65 subjects; of the 32 toxicities, the most
frequent were: menstrual changes (8),
abdominal pain/cramping (3), and headache (3).
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Regimen |
n |
Mean loge AUC 0-12h (ng×h/mL) |
p value |
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|
Without DMPA (Week 0) |
With DMPA (Week 4) |
|||
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NVP + NRTI |
13 |
10.98 |
11.14 |
0.048 |
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EFV + NRTI |
14 |
3.56 |
3.50 |
NS |
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NFV + NRTI |
20 |
10.49 |
10.29 |
NS |
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M8* + NRTI |
20 |
8.78 |
8.84 |
NS |
*
Active metabolite of NFV
Conclusions: Efficacy of DMPA among HIV+ women
does not appear to be altered in the presence of NFV-, EFV-, and NVP-based
regimens, with no evidence of ovulation occurring based on progesterone levels
through week 12. DMPA was well-tolerated and side effects were similar to those
reported in HIV– women on DMPA. NFV- and EFV-based regimens do not
appear to be altered by the presence of DMPA. Although NVP AUC levels were
higher with DMPA, the increased levels do not appear to be clinically relevant.
DMPA appears to be safe and effective for HIV-infected women taking these PI
and NNRTI.
Keywords: Antiretroviral pharmacokinetics ; Drug Interactions; Female Contraception
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