High rate of trichomonas treatment failure in women with HIV

A study of recurrent Trichomonas vaginalis infections among women in Louisiana has found similarly high rates of treatment failure for this infection among both HIV-positive and HIV-negative women, indicating that current treatment recommendations may be inadequate. Additionally, the HIV-positive women had higher rates of recurrence due to sexual re-exposure, indicating ongoing unprotected sexual behaviour. The results were published in the April 1 issue of Clinical Infectious Diseases.

Trichomonas vaginalis is a sexually transmitted infection that can lead to complications, especially in pregnant women.

The current standard treatment is a single 2g dose of metronidazole; alternately, a single 2g dose of tinidazole or 500 mg metronidazole twice daily for seven days may be prescribed. Success rates of single-dose metronidazole treatment have ranged from 90% to 95% in clinical trials.

Recurrence rates of 5% to 8% among women, and up to 30% among HIV-positive women, have been documented; both reexposure and treatment failure due to drug resistance are possible causes of recurrence.

This trial compared recurrence rates of T. vaginalis infection among HIV-positive and HIV-negative women and assessed the reasons for recurrence. The study consisted of secondary analyses of data from two separate cohorts (in studies by the same investigator) of women with T. vaginalis infection. Both were enrolled from New Orleans outpatient clinics: a group of 301 HIV-negative women enrolled between September 2001 and December 2003, and a cohort of 60 HIV-positive women recruited during 2002 and 2003.

Of the 60 HIV-positive women, 20.3% were under 30 years of age, 91.7% were black, and 79.3% had a high school education or less. Although more than half (56.7%) were on antiretroviral therapy [ART], only 6% had undetectable viral loads, and 30.0% had CD4 cell counts <200 cells/mm³. In the previous four weeks, 73.3% reported 1 sexual partner and 20.0% reported no sexual partners; 35.0% reported having unprotected sex during the one-month follow-up period.

Of the 301 HIV-negative women, 74.0% were under 30 years old, nearly all (99.0%) were black, and 58.1% had a high school education or less. In the past two months, 12.1% had more than 1 sexual partner.

All of the women were retested for T. vaginalis one month after initial treatment with single-dose (2g) metronidazole. Persistent or recurrent infection was much more common among the HIV-positive women (18.3% vs. 8.0%; p=.01). Probable causes of the recurrence were classified as either treatment failure, reinfection from the same sexual partner, or infection from a new sexual partner. Probable treatment failure rates were similar in both groups (HIV+, 10.0% vs. HIV-, 7.3%; p=.44), while reinfections from the same partner (5.0% vs. 0.7%; p=.03) or a new partner (3.3% vs. 0%; p=.03) were higher in the HIV-positive women.

Higher doses of metronidazole were successful in three of the six HIV-positive women and 17 of the 22 HIV-negative women with probable treatment failure. Mild or moderate in vitro resistance to metronidazole was found in two of the remaining three HIV-positive women and three of the remaining five HIV-negative women (3.3% vs. 1.0% of the overall cohorts; p=.19).

The findings of this study, although drawn from a single geographic location (New Orleans), illustrate several points.

Firstly, the relatively high rates of treatment failures, regardless of HIV status, "are a cause for concern because of the reproductive health consequences and because of the link between T. vaginalis infection and HIV transmission," especially as many of the women who tested positive for recurrent infection were asymptomatic (36% of the HIV-positive women and 75% of the HIV-negative women). The authors believe that these findings "suggest that the 2-g dose of metronidazole is not adequate … in some women."

Secondly, the HIV-positive women in this study were more likely to become reinfected, either by the same or by a new sexual partner, compared with HIV-negative women. This corroborates several previous findings "that [some] women continue high-risk sexual behavior despite receiving a diagnosis of HIV infection and underscore the need to increase efforts to promote safer sex among these women."

Lastly, while not explicitly discussed by the authors in this report, the high frequency of low CD4 cell counts and detectable viral loads in the HIV-positive cohort, despite the fairly widespread use of ART, is worrisome. More intensive work may be needed to help improve the response to therapy and decrease the rates of sexually transmitted infections in this and similar urban populations.

References

Kissinger P et al. Early repeated infections with Trichomonas vaginalis among HIV-positive and HIV-negative women. Clinical Infectious Diseases 46:994-999; 2008.

Kissinger P et al. Patient-delivered partner treatment for Trichomonas vaginalis infection: a randomized controlled trial. Sex Trans Dis 33:445-450; 2006.

Kissinger P et al. Vaginal swabs versus lavage for detection of Trichomonas vaginalis and bacterial vaginosis among HIV-positive women. Sex Transm Dis 32:227-230; 2005.