One Dose versus Three Weekly Doses of Benzathine Penicillin G for Patients Co-Infected with HIV and Early Syphilis: A Multicenter, Prospective Observational Study

<div><p>Background</p><p>One dose of benzathine penicillin G (BPG) has been recommended for HIV-infected patients with early syphilis (primary, secondary, and early latent syphilis) in the sexually transmitted diseases treatment guidelines, but clinical data to support such a recommendation are limited.</p><p>Methods</p><p>We prospectively observed the serological response to 1 or 3 weekly doses of BPG in HIV-infected adults who sought treatment of early syphilis at 8 hospitals around Taiwan. Rapid plasma reagin (RPR) titers were followed every 3–6 months after treatment. The serological response was defined as a 4-fold or greater decline in RPR titers at 12 months of treatment. The missing values were treated by following the last-observed-carried-forward principle. We hypothesized that 1 dose was non-inferior to 3 weekly doses of BPG with the non-inferiority margin for the difference of serological response set to 10%.</p><p>Results</p><p>Between 2007 and 2012, 573 patients completed at least 12 months of follow-up: 295 (51.5%) receiving 1 dose of BPG (1-dose group) and 278 (48.5%) 3 doses (3-dose group). Overall, 198 patients (67.1%; 95% confidence interval [CI], 61.4–72.5%) in the 1-dose group achieved serological response at 12 months, as did 208 patients (74.8%; 95% CI, 69.3–79.8%) in the 3-dose group (one-sided 95% CI of the difference, 15.1%). In the multivariate analysis, secondary syphilis (adjusted odds ratio [AOR], 1.90; 95% CI 1.17–3.09), RPR titer ≥32 (AOR, 1.93; 95% CI, 1.38–2.69), and 3 doses of BPG (AOR, 1.68; 95% CI, 1.20–2.36) were independently associated with a serological response. The time to the first episode of treatment failure was 1184 (standard deviation [SD], 70.5) and 1436 (SD, 80.0) days for 1- and 3-dose group, respectively.</p><p>Conclusions</p><p>Single-dose BPG resulted in a higher serological failure rate and shorter time to treatment failure than 3 weekly doses of BPG in the treatment of early syphilis in HIV-infected patients.</p></div

Factors associated with serological response in the patients who received 1 dose or 3 doses of benzathine penicillin G at 12 months of follow-up in univariate and multivariate analysis.

<p><b>Abbreviations:</b> CART, combination antiretroviral therapy; IQR, interquatile range; PVL, plasma HIV RNA load; RPR, rapid plasma reagin; SD, standard deviation.</p><p>Factors associated with serological response in the patients who received 1 dose or 3 doses of benzathine penicillin G at 12 months of follow-up in univariate and multivariate analysis.</p

Forest plot showing the serological response rates in different subgroups of patients receiving 1 or 3 doses of benzathine penicillin G at 12 months of follow-up.

<p>Forest plot showing the serological response rates in different subgroups of patients receiving 1 or 3 doses of benzathine penicillin G at 12 months of follow-up.</p

Serological response rates in the 1-dose and 3-dose benzathine penicillin G groups at 6 months and 12 months of follow up.

<p>A). Last-observed-carried-forward analysis; B). Per-protocol analysis.</p

Study flow showing patient recruitment and patients with available rapid plasma reagin (RPR) data during the 6 and 12 months of follow-up.

<p>Study flow showing patient recruitment and patients with available rapid plasma reagin (RPR) data during the 6 and 12 months of follow-up.</p

Multivariate analysis for factors associated with positive HBsAg.

<p>Multivariate analysis for factors associated with positive HBsAg.</p

Comparisons of the proportions of persons with positive HBsAg (HBsAg), all-negative HBV markers (All-negative), vaccination serology (Vaccination), and positive anti-HBc (anti-HBc) among HIV-infected men who have sex with men (MSM) born during 1984–1985 (HIV[+] MSM 1984), HIV-infected MSM born in or after 1986 (HIV[+] MSM 1986), HIV-uninfected MSM and heterosexuals born in or after 1986 (HIV[−] MSM 1986 and (HIV[−] Hetero 1986).

<p>Comparisons of the proportions of persons with positive HBsAg (HBsAg), all-negative HBV markers (All-negative), vaccination serology (Vaccination), and positive anti-HBc (anti-HBc) among HIV-infected men who have sex with men (MSM) born during 1984–1985 (HIV[+] MSM 1984), HIV-infected MSM born in or after 1986 (HIV[+] MSM 1986), HIV-uninfected MSM and heterosexuals born in or after 1986 (HIV[−] MSM 1986 and (HIV[−] Hetero 1986).</p

Kaplan-Meier plot showing the time to treatment failure to 1- or 3-dose benzathine penicillin G regimen (Log rank test, <i>P</i> = 0.026).

<p>Kaplan-Meier plot showing the time to treatment failure to 1- or 3-dose benzathine penicillin G regimen (Log rank test, <i>P</i> = 0.026).</p

Boxplot of anti-HBs titers in HIV-infected MSM born during 1984-1985 and HIV-infected MSM born in or after 1986.

<p>Boxplot of anti-HBs titers in HIV-infected MSM born during 1984-1985 and HIV-infected MSM born in or after 1986.</p

Clinical characteristics of HIV-infected men who have sex with men (MSM) who were born during 1984–1985, HIV-infected MSM born in or after 1986, HIV-negative MSM born in or after 1986, and HIV-negative heterosexuals born in or after 1986.

a<p>Comparison among the four groups.</p>b<p>Comparison between Groups I and II.</p>c<p>Comparison among the three groups born in or after 1986 (Groups II-IV).</p><p><b>Abbreviations:</b> anti-HBc, hepatitis B virus core antibody; HBV, hepatitis B virus; HBsAg, HBV surface antigen; HCV, hepatitis C virus; RPR, rapid plasma reagin; PVL, plasma HIV RNA load; SD, standard deviation.</p