- Category: Pre-exposure Prophylaxis (PrEP)
- Published on Wednesday, 15 February 2017 00:00
- Written by Gus Cairns
Use of the antibiotic doxycycline as on-demand post-exposure prophylaxis by men who have sex with men taking part in the Ipergay HIV PrEP trial produced a 70% drop in chlamydia infections and a 73% drop in syphilis, but no reduction in gonorrhea, according to a late-breaking report at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) this week in Seattle.
The antibiotic prophylaxis is described as "post-exposure" because trial participants were told to take it after episodes of risky sex. But they were provided with 2 months’ supply of the drug per visit and could take up to a maximum of 6 pills per week.
This is the second test of this concept, though the first study, in 2015, only recruited 30 men – see this report.
The study randomized 232 men participating in the Ipergay PrEP study in France so that half of them were provided with doxycycline to take after possible exposures to sexually transmitted infections (STIs) and half were not. Those with doxycycline were told to take a 200 mg pill up to 72 hours after each episode, though in practice nearly all who did take a pill took it within 24 hours. After a few discontinuations, 212 men -- 106 in each arm -- completed the study.
The study participants characteristics were the same as those for the Ipergay study overall: all were gay men, with an average age of 38, and the majority were white, well-educated, and employed, with 30% in a primary relationship. The average number of sexual acts in the prior 4 weeks was 10, and 42% had taken "psychoactive drugs" in the last year (methamphetamine, amphetamine, cocaine, crack, ecstasy, or GHB/GBL).
About 20% had taken HIV post-exposure prophylaxis while in the Ipergay trial. As in the PROUD study, this was allowed in situations where people had had a risky exposure and were uncertain whether they were covered by PrEP. At baseline, 10% in the doxycycline arm and 14% in the control arm were diagnosed with gonorrhea, chlamydia, or syphilis.
Over a median follow-up time of 8.7 months, there were 47% fewer infections with the 3 STIs combined in men in the doxycycline study arm than in men who did not receive the antibiotic. There were 48 infections in the control arm and 28 in the doxycycline arm. This equates to very high STI annual incidences of 70% and 38%, respectively.
However the doxycycline had no effect on gonorrhea. There were 25 gonorrhea infections in the control arm and 22 in the doxycycline arm (annual incidences of 34.5% and 29%, respectively), which is not a statistically significant difference. here were somewhat fewer cases of rectal and urethral gonorrhea in doxycycline users, but slightly more throat infections.
In contrast, the doxycycline clearly had an effect on chlamydia and syphilis. There were 70% fewer chlamydia infections in the doxycycline arm than in the control arm: 7 (annual incidence 8.7%) versus 21 (annual incidence 29%). There were only 3 syphilis infections among men taking doxycycline (incidence, 3.7% a year) and 10 in the control arm (13% a year), meaning that there was a 73% reduction in syphilis infections.
Adherence to the doxycycline was generally good. 83% of participants used it at least some of the time after potentially risky condomless sex and 49% used it every time. There was a slight decline in use over the 8 months, with the proportion of men using it every time falling from 56% to 43%, but the proportion using it at least some of the time stayed the same.
The number of sexual partners or occasions of sex did not change over the study, but the proportion reporting condomless anal sex -- already high -- increased from 80% to 90% over the course of the study, with no difference between the doxycycline and control arms. There were 8 men who discontinued doxycycline due to adverse events: the main drug-related side effect were nausea and abdominal pain, though not diarrhea. There were no laboratory abnormalities attributable to doxycycline during the study. There were 3 incident hepatitis C virus infections, 1 in the doxycycline arm and 2 in the control group.
Can We Take This Idea Forward?
So where does this leave us?
Presenter Jean-Michel Molina from Hôpital St Louis in Paris commented that this was a short study, and the longer-term benefit of such STI prophylaxis is still unknown. The 73% reduction in syphilis was potentially very useful, as this disease could have quite serious manifestations such as ocular syphilis. There was also little evidence so far of significant antibiotic resistance developing in people with either chlamydia or syphilis.
Gonorrhea is a different story. The lack of effect of doxycycline is not surprising given that 50%-75% of gonorrhea strains in France have low-level resistance to tetracycline antibiotics. In a separate presentation the previous day, Molina showed gonorrhea's continuous development of antibiotic resistance ever since the first sulphonamide antibiotics were used against it in the 1930s. While single drugs such as azithromycin and ceftriaxone would be used against it as late as 2000, it may now take 3 to 4 drugs to cure it -- and the rise of untreatable strains is forecast.
While gonorrhea normally causes no more than unpleasant inflammation and discharge, a significant percentage of both men and women get inflammation that can cause sterility, and in the case of syphilis, a small percentage develop systemic syphilis that can cause arthritis and heart valve defects.
So while Molina's trial shows a proof of concept that syphilis, at least, could be reduced as a circulating disease in gay men, it may be difficult to choose an antibiotic that does not add to the problem of resistant gonorrhea. In the absence of a clear direction forward for this strategy, condom use remains the best strategy against STIs.
J-M Molina, I Charreau, C Chidiac, et al. On demand post exposure prophylaxis with doxycycline for MSM enrolled in a PrEP trial. Conference on Retroviruses and Opportunistic Infections. Seattle, February 13-16, 2017. Abstract 91LB.