Resistance and prevalence implications of doxycycline post-exposure prophylaxis for gonorrhea prevention in men who have sex with men: a modeling study

Abstract

Background Doxycycline post-exposure prophylaxis (DoxyPEP) has demonstrated efficacy for prevention of bacterial sexually transmitted infections. To inform policy decisions on the use of DoxyPEP for gonorrhea prevention, we used a mathematical model to investigate its impact on resistance dynamics and the burden of infection in men who have sex with men (MSM). Methods and Findings Using a deterministic compartmental model of gonorrhea transmission in an MSM population, we introduced DoxyPEP at various uptake levels (10-75%) and compared 20-year prevalence and resistance dynamics relative to those at baseline (i.e., no DoxyPEP introduction). Uptake of DoxyPEP resulted in initial drops in the prevalence and incidence of gonorrhea infection, but also accelerated the spread of doxycycline resistance, with increasing DoxyPEP use driving steeper initial declines followed by faster spread of resistance. This resulted in the total loss of DoxyPEP's clinical efficacy within 1-2 decades in almost all scenarios explored. The magnitude by which DoxyPEP initially reduced the prevalence of infection was constrained by the extent of pre-existing doxycycline resistant strains in the population. De novo emergence of doxycycline resistance did not influence these dynamics. Additionally, the implementation of DoxyPEP had minimal impact on extending the clinically useful lifespan of ceftriaxone monotherapy. Conclusions Model findings suggest DoxyPEP can be an effective but short-term solution for reducing the burden of gonorrhea infection, as its selection for doxycycline-resistant strains results in loss of its prophylaxis benefit. Increasing levels of DoxyPEP uptake and higher starting prevalence of doxycycline resistance resulted in faster loss of its efficacy and had little change on extending the clinical lifespan of ceftriaxone for treatment of N. gonorrhoeae infections.

Doxycycline prophylaxis for bacterial sexually transmitted infections: evaluating effectiveness, risks, and challenges

“…Increasing DoxyPEP uptake and higher initial doxycycline resistance prevalence accelerated the loss of efficacy and had minimal impact on extending the clinical lifespan of ceftriaxone for N. gonorrhoeae treatment. The model suggested that while DoxyPEP is effective in the short-term its reduction in cumulative infections was only around 13.5-14.6% at 20 years, and it hastens doxycycline resistance to 87% within 1.8-14.1 years, depending on uptake (10-75%) 43 .…”

STI pathogens in the oropharynx: update on screening and treatment

“…Future trials assessing oropharyngeal gonorrhoea treatments should collect comprehensive pharmacokinetic data so that their doses can be optimised using robust modelling methods [129] and the use of in-vitro models may help to identify drugs that are distributed into oral tissue before being tested in clinical trials to improve successful outcomes [130] given only 13% of infectious diseases drugs entering clinical trials get FDA approval, most discarded in phase 2 [131]. Lastly, it remains uncertain what the effects will be of emerging interventions such as doxycycline postexposure prophylaxis on the development of oropharyngeal gonorrhoea incidence and drug resistance and the role of meningococcal vaccines as preventive measures [132,133,134 ▪ ,135 ▪▪ ,136,137,138 ▪▪ ,139–141].…”

Estimating Partnership Duration among MSM in Belgium—A Modeling Study

“…Several modeling studies have described the transmission of CT and NG among MSM [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ], which cluster in a few Western countries, mainly from the US [ 9 , 13 , 14 , 19 , 25 , 26 , 27 , 28 , 35 , 36 ] and Australia [ 18 , 22 , 23 , 24 , 32 , 40 , 41 , 42 , 43 ]. In Europe, notable modeling studies have been conducted in the UK [ 31 , …”

“…Several modeling studies have described the transmission of CT and NG among MSM , which cluster in a few Western countries, mainly from the US [9,13,14,19,[25][26][27][28]35,36] and Australia [18,[22][23][24]32,[40][41][42][43]. In Europe, notable modeling studies have been conducted in the UK [31,37,38,45] and The Netherlands [17,29,30,33,39,44], with few papers from France [34], Belgium [8,16] and Switzerland [20,21].…”