Role of Gender in Response to Efavirenz-containing Regimens in Antiretroviral-naive HIV Patients

By Ronald Baker, PhD

The number of women seeking care at clinics in the United Kingdom has increased substantially in recent years. As a result, researchers feel it is important to evaluate whether response to antiretroviral treatment is comparable across all subgroups of patients.

Prior studies that have examined the role of gender and response to therapy have discovered similar treatment responses in men and women, but also higher drug discontinuation rates in women. One study found better virological outcomes among women*.

British researchers conducted a study to assess the role of gender in the treatment outcomes of HIV positive, antiretroviral-naive individuals who were receiving regimens containing the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva pr Stocrin), which in recent years has been the most commonly used initial HAART regimen in the UK.

Accepted for publication in the Journal of Acquired Immune Deficiency Syndromes in July 2007, the study results will appear in a forthcoming issue of the journal later this year.

The investigators enrolled patients at the Royal Free Hospital in London. All previously antiretroviral-naive individuals starting efavirenz from 1996 onward were included. Of 433 total patients enrolled, 96 were women, of whom 64.6% were black and in the heterosexual risk category; most of the men (71.2%) were white and in the homosexual risk category.

This was a prospective study in which information was obtained as patients came to the clinic for care. The information collected included demographics, all prior AIDS diagnoses, use of Pneumocystis jiroveci pneumonia (PCP) prophylaxis, treatment start and stop dates, reasons for stopping all antiretroviral drugs, and adherence.

Treatment failure was defined as the first of 2 consecutive viral load measurements >500 copies/mL more than 24 weeks after starting efavirenz. Standard survival methods were used to assess time to discontinuation and to treatment failure.

Results

• Women had lower CD4 cell counts when starting efavirenz compared with men (median 126 cells/mm3 vs. 190 cells/mm3; P = 0.0003).

• After 48 and 96 weeks, 38.8% and 56.3% of the women had discontinued efavirenz, compared with 28.3% and 41.8% of the men (P = 0.005).

• The percentages experiencing treatment failure by 48 and 96 weeks (ignoring treatment changes, but censoring at the date of discontinuation of all treatment) were 1.3% and 4.4% for women, compared with 3.8% and 5.8% for men.

• Median CD4 count increases at 48 weeks were 166 cells/mm3 for women and 176 cells/mm3 for men.

Based on these results, the study authors concluded, "Women seem to have comparable virologic and immunologic outcomes to first-line efavirenz-containing regimens compared with men, although they are more likely to discontinue the drug."

Discussion

This study showed that a higher proportion of women discontinued efavirenz compared with men, in agreement with other studies. It has been suggested that this may be related to greater toxicity among women, as a result of lower body mass index and higher drug levels. Ethnic differences also might have affected plasma drug levels.

Although the investigators found similar changes from pretreatment levels in laboratory markers for various toxicities in men and women, they obtained no information on the occurrence of central nervous system (CNS) toxicities or depression using these markers. However, they did find that a high proportion of patients stopped efavirenz for ''other'' reasons, which could have included CNS toxicity concerns.

They also found that women had lower pretreatment CD4 cell counts. "Thus, they could perhaps have been sicker and more likely to be receiving concomitant medications than men, which may lead to higher treatment discontinuation rates," wrote the authors. Finally, women who became or were considering becoming pregnant may discontinue efavirenz, according to the authors. (Efavirenz is contraindicated for pregnant women because it can cause birth defects.)

The researchers concluded that treatment responses in men and women were comparable in this study. "Only when considering switching from efavirenz as failure did we observe differences in response between men and women," they stated. "This is consistent with the finding that women are more likely to discontinue efavirenz than men."

The authors found no factors associated with treatment failure, and they observed similar CD4 cell count changes in men and women, confirming the findings of several other studies.

In summary, the study authors found that individuals receiving efavirenz-containing antiretroviral regimens as their first-line antiretroviral regimen "had a low risk of experiencing actual virologic failure, and this did not differ between genders."

Finally, they concluded, "A reasonably high rate of treatment discontinuations and switches was observed, however, in line with other observational studies,
with women more likely to discontinue efavirenz than men."

08/24/07

References

C J Smith, J Colette, C A Sabin, and others. Response to Efavirenz-Containing Regimens in Previously Antiretroviral-Naive HIV-Positive Patients: The Role of Gender. Journal of Acquired Immune Deficiency Syndromes. Published online ahead of print July 19, 2007.

* A Moore, A Mocroft, S Madge, and others. Gender differences in virologic response to treatment in an HIV-positive population: a cohort study. Journal of Acquired Immune Deficiency Syndromes 26: 159-163. 2001.