Gonorrhea is the Chink in DoxyPEP's Armor

By: Marcus J. Hopkins, Health Policy Lead Consultant, ADAP Advocacy

Recent studies have shown that DoxyPEP (doxycycline post-exposure prophylaxis) is becoming less effective against the bacterial sexually transmitted infection (STI) gonorrhea. Concerns are rising among certain public health groups, such as the Centers for Disease Control & Prevention and European counterparts, but Doxy-PEP remains regarded as a highly effective prevention method for high-risk groups.

Photo Source: Harvard Health Publishing

For the uninitiated, DoxyPEP is a post-exposure oral medication provided within 72 hours after a sexual encounter that reduces the likelihood of acquiring bacterial STIs, including syphilis, chlamydia, and gonorrhea. In the initial DoxyPEP trial, researchers found that the incidence of syphilis decreased by 87%, chlamydia by 88%, and gonorrhea by 55% (Dall, 2026). After this initial study, the Centers for Disease Control and Prevention (CDC) released clinical guidelines for its utilization in 2024 (Bachmann et al., 2024).

Even in the initial study, the reduced incidence of gonorrhea was modest, at best; subsequent studies have shown that a rapid increase in tetracycline-resistant strains of gonorrhea has greatly reduced or all but eliminated DoxyPEP’s efficacy against the infection.

Research published in JAMA Internal Medicine found that the incidence of STI cases of syphilis and chlamydia in San Francisco, CA, decreased significantly among Men who have Sex with Men (MSM) and transgender women against projected case numbers, while the incidence of gonorrhea increased significantly (Sankaran et al., 2025).

Another study published in Clinical Infectious Diseases suggests that widespread utilization of DoxyPEP may actually be contributing to the increase in tetracycline-resistant gonorrhea strains in King County, Washington state, which has resulted in the county health department revising its guidelines on the utilization of doxycycline to treat other bacterial issues, including skin and soft tissue infections and lower respiratory tract infections (Soge et al., 2025).

A third study published in The Lancet Infectious Diseases similarly suggests that widespread utilization of DoxyPEP may be inadvertently increasing the propagation of multidrug-resistant strains of gonorrhea in southern California (Yechezkel et al., 2026).

Photo Source: emedicinehealth.com

Drug-resistant strains of gonorrhea have been a concern in the United States for some time, and researchers have been sounding the call against overreliance upon DoxyPEP as a harm reduction tool against the STI for just as long. A correspondence published in the New England Journal of Medicine in 2025 warned that multidrug-resistant strains have been spreading globally, including strains that carry resistance to the antibiotic ceftriaxone (Helekal et al., 2025).

Sexual health advocates have been heralding DoxyPEP as one of the first effective methods for preventing STIs transmission since the findings of the initial study, including those at the American Sexual Health Association (ASHA, 2025). There is no doubt that DoxyPEP has clearly been shown to be effective against syphilis and chlamydia; however, ADAP Advocacy recommends that organizations begin having realistic conversations about its efficacy against, as well as the continued increase in propagation of, multidrug-resistant strains of gonorrhea.

These conversations need not be “sex-negative,” focusing on fear and shame-based representations of sexual activity; they do, however, need to be realistic.

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Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association; rather, they provide a neutral platform for the author to promote open, honest discussion of public health-related issues and updates.

References:

[1] American Sexual Health Association. (2025, May 09). Learn More About Doxy PEP from Three People Who Take It. Research Triangle Park, NC: American Sexual Health Association. https://www.ashasexualhealth.org/learn-more-about-doxy-pep-from-three-people-who-take-it/

[2] Bachmann, L. H., Barbee, L. A., Chan, P., Reno, H., Workowski, K. A., Hoover, K., Mermin, J., & Mena, L. (2024, June 06). CDC Clinical Guidelines on the Use of Doxycycline Postexposure Prophylaxis for Bacterial Sexually Transmitted Infection Prevention, United States, 2024. Morbidity and Mortality Weekly Report Recommendations and Reports, 73(2): 1-8. http://dx.doi.org/10.15585/mmwr.rr7302a1

[3] Dall, C. (2026, May 11). Study shows doxyPEP’s diminished effectiveness against gonorrhea. Minneapolis, MN: University of Minnesota: Research and Innovation Office: Center for Infectious Disease Research and Policy: Antimicrobial Stewardship. https://www.cidrap.umn.edu/antimicrobial-stewardship/study-shows-doxypep-s-diminished-effectiveness-against-gonorrhea

[4] Helekal, D., Mortimer, T. D., & Grad, Y. H. (2025, July 09). Expansion of tetM-Carrying Neisseria gonorrhoeae in the United States, 2018–2024. New England Journal of Medicine, 393(2), 198-200. https://doi.org//10.1056/NEJMc2504010

[5] Sankaran, M., Glidden, D. V., Kohn, R. P., Nguyen, T. Q., Bacon, O., Buchbinder, S. P., Gandhi, M., Havlir, D. V., Liebi, C., Luetkemeyer, A. F., Nguyen, J. Q., Roman, J., Scott, H., Torres, T. S., & Cohen, S. E. (2025, January 06). Doxycycline Postexposure Prophylaxis and Sexually Transmitted Infection Trends. JAMA Internal Medicine, 185(3), 266-272. https://doi.org/10.1001/jamainternmed.2024.7178

[6] Soge, O. O., Thibault, C. S., Cannon, C. A., McLaughlin, S. E., Menza, T. W., Dombrowski, J. C., Fang, F. C., & Golden, M. R. (2025, June). Potential Impact of Doxycycline Post-Exposure Prophylaxis on Tetracycline Resistance in Neisseria gonorrhoeae and Colonization With Tetracycline-Resistant Staphylococcus aureus and Group A Streptococcus. Clinical Infectious Diseases, 80(6), 1,188-1,196. https://doi.org/10.1093/cid/ciaf089

[7] Yechezkel, M., Helekal, D., Kapadia, B., Hong, V., Pomichowski, M. E., Reyes, I. A. C., Davis, G. S., Müller, N. F., Grad, Y. H., Tartof, S. Y., & Lewnard, J. A. (2026, May 07). Durability of doxycycline effectiveness against gonorrhoea after implementation of post-exposure prophylaxis in southern California, USA: a retrospective, test-negative, observational study. The Lancet Infectious Diseases. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00123-4/fulltext

Start Antiretroviral Therapy Sooner Than Later

By: Ranier Simons, ADAP Blog Guest Contributor

As medical science strives towards eradicating HIV, research and discourse regarding treatment and prevention continue to evolve. Antiretroviral therapy (ART) is the primary method of treatment. ART is drug therapy consisting of various combinations of medications whose purpose is reducing the HIV viral load in the body. The ultimate goal is to reduce the viral levels in the body to the point of being undetectable. Undetectable means that the viral load is so low that a viral load test cannot detect it.[1] Reaching undetectable status means that a person has no risk of sexually transmitting HIV to others, commonly referred to as "U=U" (undetectable equals untransmittable). Research has also shown that maintaining undetectable status enables people living with HIV/AIDS (PLWHA) to live long, healthy lives. 

Photo Source: Very Well Health

The timeline of starting patients on treatment is an ongoing inquiry at the forefront of ART discourse. In addition to viral load, historically, many other factors have been considered when starting PLWHA on drug therapy. Those who are asymptomatic and seemingly very healthy with good CD4 counts sometimes don’t see the benefits of starting early treatment out of concerns about possible long-term side effects and emotionally handling the prospect of lifetime medication adherence.[2] Notwithstanding various psychosocial, financial, and logistical issues, the main clinical criteria inquiry is the CD4 count. 

CD4 cells are white blood cells in the body that help the immune system to fight infection. HIV attacks and destroys CD4 cells.[3] An insufficient number of CD4 cells leaves the body susceptible to many forms of illness that healthy HIV-negative people are protected against. PLWHA are diagnosed with AIDS when the CD4 count reaches 200 cells/mm3.AIDS diagnosis means a high risk of developing life-threatening illnesses or even cancers.

Over time consensus has evolved regarding the appropriate CD4 count threshold for beginning ART. For a long time, the established guidelines recommended ART to begin when CD4 counts dropped below 350 cells/mm3 or if a patient had symptoms of AIDS. In December 2009, U.S. guidelines were issued, including a recommendation that ART commences if the CD4 count is between 350 and 500 cells/mm3.[4] However, that recommendation was based on observational studies, not randomized trials, in the manner that previous guidelines were developed. A randomized trial results in more definitive information since randomization means groups tested are very similar except for received treatment.[4]

To obtain randomized trial results concerning early ART intervention, the Strategic Timing of Antiretroviral Therapy (START) trial was first initiated in 2009, enrolling 4,684 HIV-positive patients (median age 36, 27% women), who had a CD4 count of ≥500 cells/mm3 (median 651 cells/mm3 ) at least two weeks apart within the 60 days before enrollment. Of these patients, 2,325 were randomized to start ART immediately, and 2,359 were randomized to defer treatment until their CD4 count was ≤350 cells/mm3.[5] Subjects were followed for a minimum of three years. START is a multinational endeavor.

Photo Source: everydayhealth.com

In 2015, results were published in the New England Journal of Medicine. Data showed that early initiation of ART lowered the risk of severe AIDS-related outcomes, serious non-AIDS-related outcomes, and death by 57%.[4] When the results were published, the subjects who had previously been in the deferred ART group started drug therapy. Another analysis was done in October 2022, which included 4,436 patients who were followed from January 2016 through December 2021. This analysis supported the benefits of starting ART early, even for patients with CD4 counts over 500 cells/mm3 at diagnosis. An additional finding was that adverse outcomes of delayed treatment were more pronounced in patients aged 35 and younger.[4] Research is continuing to examine the outcome difference by age.

Given that the START study shows the importance of early initiation of ART, it is imperative to increase efforts to identify HIV-positive patients. Many people don’t find out until clinically, a lot of damage has occurred. By increasing testing efforts, especially for those in higher-risk groups, HIV infection can be caught at earlier stages, and patients can initiate therapy. Early therapy means a much lower risk of AIDS progression, fewer instances of non-AIDS-related serious issues, and shorter time spans to reaching undetectable status. Diagnosing people earlier means a better quality of life for those infected and an expedited reduction in the number of people with viral loads high enough to be a transmission risk.

[1] National Institute of Health. (2021, August 16). HIV Treatment. Retrieved from https://hivinfo.nih.gov/understanding-hiv/fact-sheets/when-start-hiv-medicines#:~:text=When%20is%20it%20time%20to,possible%20after%20HIV%20is%20diagnosed
[2] Ross, J. et al. (2021) How early is too early? Challenges in ART initiation and engaging in HIV care under Treat All in Rwanda-A qualitative study. PloS one, 16(5), e0251645. https://doi.org/10.1371/journal.pone.0251645
[3] National Institute of Health. (2022, August 22). CD4 Lymphocyte Count. Retrieved from https://medlineplus.gov/lab-tests/cd4-lymphocyte-count/
[4] Hein, I. (2022, October 25). Start HIV Antiretroviral Therapy ASAP, Experts Urge. Retrieved from https://www.medpagetoday.com/meetingcoverage/idweek/101419
[5] National Institute of Health. (October 4, 2022). Strategic Timing of Antiretroviral Treatment (START). Retrieved from https://clinicaltrials.gov/ct2/show/study/NCT00867048

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates. 

HIV & Monkeypox: What Patients Need to Know

By: Ranier Simons, ADAP Blog Guest Contributor

Presently, there is not much research data concerning monkeypox and HIV. Due to the novelty of the recent monkeypox outbreak, there has not been enough time or volume of subjects to complete many studies. Monkeypox is a type of virus known as orthopoxviral. Smallpox is also an orthopox virus which is why the smallpox vaccine is used to protect against monkeypox. However, smallpox was eradicated in 1980 before the HIV/AIDS epidemic.[1] Additionally, monkeypox has existed for years in areas where it has been endemic, yet research has been neglected and underfunded.[2] Many questions need to be investigated. Medical science has already proven that T-cell deficiencies due to HIV render HIV-positive people more susceptible to viral and fungal infections.[1] Two main questions are: does HIV infection increase the risk of contracting monkeypox, and is HIV an aggravating factor in monkeypox infection/progression/severity? 

Photo Source: International Business Times

There is some medical evidence that having underlying immune deficiencies increases the risk of infection if exposed and the possibility of severe illness if infected.[5] People living with HIV are immunocompromised. However, the increased risk and negative outcomes of infection is more likely for those with untreated HIV. Untreated HIV means a much weaker immune system than those in treatment. Those in consistent medical treatment usually have well controlled HIV with many reaching viral suppression. Being undetectable results in a characteristically immunocompetent immune system more like those who are not living with HIV.[5]

The U.S. Centers for Disease Control & Prevention (CDC) last month updated its Clinical Considerations for Treatment and Prophylaxis of Monkeypox Virus Infection in People with HIV. The CDC contends that people with advanced HIV or who are not virologically suppressed with antiretroviral therapy can be at increased risk of severe disease with monkeypox, but they also note  that these considerations are based upon limited evidence available.

Two recently published studies give some developing insight into the relationship between HIV and monkeypox. One such study is a multinational study published in the New England Journal of Medicine. The study was performed by a collaborative international group of clinicians that spanned 43 sites in 16 countries.[2] Together they compiled a case series of 528 infections. In this sample set, 98% were gay or bisexual men, 2% were heterosexual men, 75% were white, 41% were HIV positive (the majority was well controlled), and the median age was 38.[2] The clinical presentation of those living with HIV and those not HIV positive were very similar, with no significant differences. 

This study confirmed sexual activity, among gay and bisexual men, as a significant transmission route. Tracking of infection indicated reports of infection clusters associated with sex parties or saunas. International travel and attendance of large gatherings linked to sex-on-site activities by some subjects support the developing theory of enhanced infection rates through sexual networks.[2] Notably, the study did not conclude that monkeypox was transmitted through semen. The genital, anal, and oral mucosal lesions were found to result from close skin-to-skin contact during sexual activity. However, testing 32 semen samples indicated results are inconclusive as to if the amounts and kinds of viral DNA found in the seminal fluid are replication competent.[2] More research is needed.

Photo Source: Physicians' Research Network

The second study was conducted in Spain. It was an observational prospective cohort study of 181 subjects from 3 sexual health clinics in Madrid and Barcelona.[3] A prospective cohort study means that the subjects are followed and observed over time to monitor the development of their outcomes. Of the 181 subjects, 166 identified as gay men or bisexual men, 15 as heterosexual men or women (6 were female), and 72 (40%) were HIV positive.[3] All of the subjects had skin lesions. Seventy-eight percent had anogenital lesions, and 43% had them in the oral and perioral regions. Additionally, other complications were observed. Proctitis was seen in 45 subjects; 19 had tonsilitis, 15 had penile swelling, and 8 had a widely spread-out rash. Notably, systemic symptoms (fever, headache, flu-like sickness, sore throat) before the appearance of rash occurred more often in those who had participated in anal-receptive intercourse than those who did not.[3]

The important takeaway from both studies is that clinicians need to expand the symptoms of what they look for in monkeypox infection. The current outbreak is not behaving like the outbreaks in the endemic area of Africa, which typically had hundreds of rashes with some as pustules. These studies showed cases where people have only had one lesion on the surface skin. Clinicians should be extra cautious and suspicious of monkeypox disease in at-risk populations. The virus can be present in atypical ways that may appear as other STIs, such as chlamydia or syphilis. Moreover, both studies showed the incubation period was, on average, about 7 to 8 days; thus, focusing energies on pre-exposure intervention is essential. 

Photo Source: The Nation

It is currently unknown how long people can spread disease after lesions have crusted over and healed. Condom use is suggested for eight weeks after healing. HIV subjects are overrepresented in the populations of the studies due to the way subjects were obtained. Subjects were picked from places like sexual health clinics where many HIV-positive patients receive treatment. Additionally, HIV-positive people with well-controlled disease are more likely to seek testing. The overrepresentation in the studies does not indicate that an HIV diagnosis necessarily equates to an increased likelihood of infection. However, more research is needed to investigate that. A recent study has also shown that a person can be simultaneously infected with HIV, Covid, and monkeypox.[4] Exploring the interaction with HIV is imperative.

Getting ahead of the current monkey pox infection wave with prevention is the most effective way to stop the current trajectory. Prevention includes behavior modification as well as testing and vaccination. Targeted  messaging to vulnerable groups will encourage behavior modification as well as testing. Widespread adoption of expanded protocols of symptom investigation by clinicians  will also increase the identification of monkeypox infection in those presenting with atypical symptoms. Halting the spread is paramount, before it has the chance to reach pandemic levels.

[1] Henderson, J. (2022, August 19). More data needed on monkeypox, HIV co-infection. Retrieved from https://www.medpagetoday.com/special-reports/exclusives/100279
[2] Thornhill, J., Barkati, S., Walmsley, S., et al. (2022). Monkeypox virus infection in humans across 16 countries — April–June 2022. New England Journal of Medicine. 387, 679-691. DOI: 10.1056/NEJMoa2207323
[3] Tarin-Vincente, E., Alemany, A., et al. (2022). Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study. The Lancet. 400(10353), 661-669. DOI:https://doi.org/10.1016/S0140-6736(22)01436-2
[4] Kneisel, K. (2022, July 26). How monkeypox can present like common STIs. Retrieved from https://www.medpagetoday.com/infectiousdisease/generalinfectiousdisease/99912
[5] World Health Organization. (2022, August 4). Monkeypox. Retrieved from https://www.who.int/news-room/questions-and-answers/item/monkeypox#:~:text=Anyone%20who%20has%20close%20contact,illness%20or%20dying%20from%20monkeypox

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.