Doxy-PEP studies at CROI 2024

Kirk Taylor, HIV i-Base

CROI 2024 included a roundtable discussion, 3 oral and 8 poster presentations on the use of doxy-PEP to treat and prevent chlamydia, gonorrhoea and early syphilis. [1-6]

Doxy-PEP was rolled out in the USA in October 2022 and is recommended for gay and bisexual men and transgender women who have had ≥1 bacterial STI in the previous year. This strategy reduced bacterial STIs by 65%.

Following doxy-PEP rollout in the USA, there has been a clear reduction in chlamydia and syphilis cases. The impact on gonorrhoea remains modest, and the prevalence of tetracycline resistant strains should be considered. [1]

Antimicrobial resistance and adherence remain key concerns for doxy-PEP. A study of gut microbiome noted dose-dependent increases of tetracycline resistance, which could lead to horizontal transmission of resistance genes. [5]

Doxy-PEP reduces chlamydia and syphilis cases, but mixed picture for gonorrhoea

The impact of doxy-PEP rollout on bacterial STIs was monitored at three clinics in San Francisco between July 2021 and November 2023. In the first year >3,700 people were prescribed doxy-PEP, with rapid uptake in the first two months by 576 people. [1]

Rates of chlamydia, syphilis and gonorrhoea were compared before and after doxy-PEP. Doxy-PEP reduced chlamydia cases by 6.6% per month and halved the number of cases within a year. Syphilis rates fell by 2.7% per month, with a significant decline immediately following introduction of doxy-PEP. It is noteworthy that syphilis case numbers were low before doxy-PEP.

Gonorrhoea case rates were not significantly altered by doxy-PEP. Before doxy-PEP was introduced, case rates were falling by 1.8% but following rollout case rates increased by 1.8%. This was surprising given previous trial data, but the authors argued that gonorrhoea rates were stable.

Doxy-PEP rollout at the Magnet Clinic in San Francisco began in November 2022. People registered for PrEP between June 2022 to September 2023 were included in the study. Analysis was stratified by doxy-PEP use (n=1,209) and SOC (n=3,081). Uptake was high (28% of PrEP users) and greatest for those who had a prior STI. [2]

Doxy-PEP introduction reduced bacterial STI incidence from 18.1% to 7.5%. Doxy-PEP significantly reduced incidence of chlamydia (-67%), syphilis (-78%) and gonorrhoea (-11%). Timeline analyses show that people who adopted doxy-PEP were more likely to have had a previous bacterial STI. People receiving SOC saw a small decline in STI incidence, down from 7.5% to 6.5%.

CROI 2024 included a poster on doxy-PEP efficacy in gay, bisexual and other men who have sex with men and transgender women taking PrEP who live in San Francisco. Bacterial STI prevalence was compared between those taking doxy-PEP (n=367) and SOC (n=139). Rollout of doxy-PEP reduced chlamydia and syphilis in high-risk people by 90% (95% CI: 79% to 95%) and 56% (relative risk: 0.44, 95% CI 8% to 79%), respectively. Gonorrhoea incidence decreased modestly but was not significant. [3]

Gay and bisexual men and transgender women taking PrEP included in the doxy-PEP study were randomised 2:1 to receive doxy-PEP or standard of care (SOC). In May 2022 an open-label extension (OLE) was granted to offer doxy-PEP to the SOC group. [4]

The OLE included 289 participants from the doxy-PEP (n=207) and SOC (n=82) groups who were followed for a median (IQR) of 6 months (3 to 9 months). In the randomised study, bacterial STI incidence was 31% for SOC compared to 12% in the doxy-PEP group. Switching to doxy-PEP in the OLE led to a 14% reduction of bacterial STIs with decreased incidence of chlamydia (-5%), syphilis (-3%) and gonorrhoea (-2%). The number of doxy-PEP doses increased from 15 (IQR 4 to 30) in the randomised study to 17 (IQR 5 to 32) in the OLE. The OLE also saw an increase in the number of sexual partners and frequency of condomless sex.

Antimicrobial resistance and monitoring adherence

Doxy-PEP is highly effective at reducing bacterial STIs but increased prescribing of antibiotics raises concerns of antimicrobial resistance. Bacterial diversity of the gut microbiome and antimicrobial resistance was assessed in an open-label study. [5] Gay and bisexual men and transgender women with ≥1 bacterial STI in the previous year were enrolled (n= 501). Participants were randomised 2:1 to receive doxy-PEP or SOC.

Rectal swabs at baseline (D0) and 6 months were analysed. Bacterial abundance and diversity were unchanged between the two groups at 6 months. There was an increase of tetracycline resistance genes at 6 months for the doxy-PEP arm. Detection of resistance genes was dose-dependent, but its clinical significance is unclear.

Use of doxy-PEP (200 mg oral dose of doxycycline) within a 72-hour window protects against transmission of chlamydia, gonorrhoea and syphilis in gay and bisexual men. However, levels of protection for women are lower and possibly linked to adherence. A PK study demonstrated that doxycycline can be detected in plasma and urine for up to 7 days and levels are comparable for men (n=11) and women (n=9). [6] Adherence testing using urine or plasma PK analysis may elucidate links between doxy-PEP adherence and efficacy for women.

COMMENT

The BHIVA ‘Best of CROI’ virtual feedback meeting included an excellent summary of doxy-PEP studies from Dr Amanda Clarke. [7]

The impact of doxy-PEP on the gut microbiome was discussed, but it is not clear whether 6 months of data is sufficient to determine no effect. Furthermore the prevalence of tetracycline resistance must be closely monitored as there is a risk of horizontal transmission into other bacteria, fuelling antimicrobial resistance.

Current BASHH guidelines only allow doxy-PEP for research purposes, but updated guidance is due in the summer 2024. This is important as people are buying doxy-PEP online and there are no formal reporting mechanisms.

US CDC guidelines on doxy-PEP were also just published. [8]

References

Unless stated otherwise, all references are to the programme and abstracts of the Conference on Retroviruses and Opportunistic Infections, 3 – 6 March 2024, Denver, Colorado, USA.
www.croiconference.org/search-abstracts

Sankaran M et al. Doxy-PEP associated with declines in chlamydia and syphilis in MSM and trans women in San Francisco. Oral abstract 127.
https://www.croiconference.org/abstract/doxy-pep-associated-with-declines-in-chlamydia-and-syphilis-in-msm-and-trans-women-in-san-francisco/ (abstract)
https://www.croiwebcasts.org/p/2024croi/croi/127 (webcast)
Scott H et al. Doxycycline PEP: high uptake and significant decline in STIs after clinical implementation. Oral abstract 126.
https://www.croiconference.org/abstract/doxycycline-pep-high-uptake-and-significant-decline-in-stis-after-clinical-implementation/ (abstract)
https://www.croiwebcasts.org/p/2024croi/croi/126 (webcast)
Bacon O et al. Doxy-PEP Effectiveness in Men Who Have Sex With Men (MSM) and Transgender Women (TGW) on HIV PrEP. CROI 2024. Poster Abstract 1151.
https://www.croiconference.org/abstract/doxy-pep-effectiveness-in-men-who-have-sex-with-men-msm-and-transgender-women-tgw-on-hiv-prep/
Luetkemeyer A et al. Sustained reduction of bacterial STIs during the DoxyPEP study open-label extension. Oral abstract 125.
https://www.croiconference.org/abstract/sustained-reduction-of-bacterial-stis-during-the-doxypep-study-open-label-extension/ (abstract)
https://www.croiwebcasts.org/p/2024croi/croi/125 (webcast)
Chu VT et al. Impact of doxycycline as STI PEP on the gut microbiome and antimicrobial resistance gene expression. Poster abstract 1154.
https://www.croiconference.org/abstract/impact-of-doxycycline-as-sti-pep-on-the-gut-microbiome-and-antimicrobial-resistance-gene-expression/
Haaland R et al. Adherence Markers for Doxy-PEP in Plasma and Urine. Poster Abstract 611.
https://www.croiconference.org/abstract/adherence-markers-for-doxy-pep-in-plasma-and-urine/
Clarke A. BHIVA ‘Best of CROI 2024’ webinar.
https://www.bhiva.org/BestofCROI2024
HTB. New CDC guidelines recommend selected use of doxy-PEP in the US (2024). HTB (June 2024).
https://i-base.info/htb/47839