Background CDC guidelines recommend azithromycin or doxycycline as treatments for chlamydial infection. Recently, one randomised trial comparing these therapies suggested doxycycline was superior, while another found the two therapies were equivalent. We examined the risk of persistent/recurrent chlamydial infection among patients treated with doxycycline or azithromycin.

Methods We performed a secondary analysis of data from Project Aware, a randomised, controlled trial of a behavioural intervention. The trial enrolled patients aged ≥ 18 years without a prior HIV diagnosis in 9 U.S. STD clinics in 2010. At baseline, women with urogenital chlamydial infection and men with urethral and/or rectal chlamydial infections were treated with azithromycin or doxycycline, per clinic standard of care. Patients with a positive chlamydia test at 6-month follow-up were considered to have persistent/recurrent infection.

Results Of 5012 participants, 492 (9.8%) tested positive for C. trachomatis at baseline. Of these, 338 (69%) were treated with doxycycline or azithromycin without a second drug active against C. trachomatis; 92% (76 of 83) and 88% (225 of 255), respectively, were re-tested at 6 months. Comparing doxycycline and azithromycin, overall 7 (9.2%) and 26 (11.6%), respectively, had persistent/recurrent infection (RR = 0.80, 95% CI = 0.36–1.76). Among persons with urogenital infections, 6 (10.0%) of 60 and 18 (10.1%) of 179 (RR = 0.99, 95% CI = 0 0.41–2.39), respectively had persistent/recurrent infection. Among men with rectal infections, 2 (9.5%) of 21 and 8 (16.3%) of 49 who received doxycycline and azithromycin, respectively, had persistent/recurrent infection (RR = 0.58, 95% CI = 0.14–2.52). On multivariate analysis, persistent/recurrent infection was significantly associated with black (vs. white) race (aRR = 4.29, 95% CI = 1.14–16.16) and rectal (vs. urogenital) infection (aRR = 5.42, 95% CI = 0.99–29.55), but not treatment regimen.

Conclusion There were no differences in persistent/recurrent urogenital chlamydia infections at six months by treatment type. Treatment failure of rectal infections among men may be more common with azithromycin and merits additional study.