One BPG dose may be enough to treat syphilis, regardless of HIV status

Three doses of benzathine penicillin G (BPG) are not necessarily better than a single dose in the treatment of early syphilis in individuals with or without HIV infection, as shown in a study.

“Treatment of persons with early syphilis with more than a single dose of 2.4 million units of BPG offers no therapeutic benefit irrespective of HIV infection status and is associated with increased rates of injection site discomfort,” reported study co-author Dr Jodie Dionne of University of Alabama at Birmingham, Alabama, US.

A total of 249 people (mean age 35 years, 97 percent men, 62 percent Black) with early syphilis were included in the intention-to-treat analysis. These participants had been randomly assigned to receive treatment with a single intramuscular injection of BPG 2.4 million units (n=124) or three BPG doses administered over three successive weeks (n=125).

Syphilis stage at diagnosis was primary for 33 percent of the participants, secondary for 44 percent, and early latent for 30 percent. The majority of the participants (61 percent) were living with HIV.

None of the participants had penicillin or beta-lactam allergy, any exposure to antibiotics active against T. pallidum in the past 30 days, and STI coinfection requiring treatment with drugs active against T. pallidum.

The primary outcome of serologic response to therapy, defined as at least a fourfold decline in rapid plasma reagin (RPR) titer, at 6 months did not significantly differ between the one-dose and three-dose arms (76 percent vs 70 percent). The nonresponse rates were also similar (21 percent vs 30 percent, respectively). [IDWeek 2023, abstract 2889]

“We did have four participants (3 percent) who met the [treatment] failure definition,” all of whom were in the single-dose group, Dionne noted. “When we looked at them, they were people whose RPR was rising at admission. We do not think that they were reinfections, but we cannot rule it out.”

When stratified by HIV status, the cumulative 6-month response was “remarkably” the same, she said. Response rates were 76 percent with a single BPG dose and 71 percent with three BPG doses for participants living with HIV (difference in proportion with serological response, –0.05, 95 percent confidence interval [CI], –0.17 to 0.07), and 76 percent and 70 percent, respectively, for participants without HIV (difference in proportion with serological response, –0.06, 95 percent CI, –0.22 to 0.09).

As for safety, Dionne pointed out that the adverse events were significant in terms of pain and tenderness, which were reported by 201 participants (81 percent) after receipt of BPG. There were 59 participants (24 percent) who had Jarisch-Herxheimer reaction symptoms. Dionne shared that she and her colleagues are gathering some more data to determine whether such symptoms are predictive of a clinical response.

Finally, three serious adverse events that were not related to the study drug occurred, including one in the single-dose arm and two in the three-dose arm. One was a hospitalization for a substance-induced psychosis, another was new neurologic signs consistent with neurosyphilis, and the third was a rectal proctocolitis. All of these were resolved.

The findings are encouraging in light of the “high rates of HIV co-infection and continuing concerns about the adequacy of single dose penicillin therapy for people living with HIV,” according to Dionne.

She also highlighted the recurring global shortage of BPG in the clinics, with physicians often told that they cannot treat patients with BPG due to the drug being reserved for pregnant women only.

“Syphilis is an emerging problem—an old problem that is getting worse and not better. In our clinics we have had more than a decade of steadily increasing syphilis rates, initially among men who have sex with men but more recently congenital infections and among people with opposite sex partners,” Dionne said. “We need to find some ways to turn this around.”