Predictors of lack of serological response to syphilis treatment in HIV-infected subjects.
BACKGROUND
The aim of this study was to determine factors associated with lack of serological response (LSR) to treatment of syphilis among HIV-infected subjects.


METHODS
Retrospective, longitudinal study on HIV-infected subjects diagnosed and treated for syphilis and with an assessable serological response between 1 January 2004 and 15 September 2013. LSR was defined as a <4-fold decline of rapid plasma reagin (RPR) titer or a failed reversion to nonreactive (if RPR ≤1:4 at diagnosis) after one year since treatment. Diagnoses of syphilis were staged in early syphilis (primary, secondary and early latent) or late syphilis (tertiary and late latent) according to clinical examination and patient's history. Syphilis was classified in new infections [NI: positive RPR and TPHA (Treponema pallidum Haemagglutination assay) titers in subjects without previous history of syphilis] or re-infections [ReI: a ≥4-fold increase of RPR titer in subjects previously successfully treated for syphilis]. Syphilis treatment was prescribed according to CDC guidelines. The crude incidence rates (IRs) of LSR were calculated per 1000-person months of follow-up (PMFU) as the total number of LSR episodes divided by the cumulative time contributed by all subjects (interval time since each syphilis diagnosis and the date of ascertainment of response). RESULTS are described as median (IQR) or frequency (%).


RESULTS
565 diagnoses of syphilis with an assessable serological response in 421 patients; 458 (81%) were early syphilis, 189 (33%) were NI, 376 (67%) were ReI. At first, diagnosis of syphilis median age was 41 (36-47) years, 419 (99.5%) males, 391 (93%) MSM, HIV-infected since 7.7 (3.5-12.9) years, 75 (18%) HCV or HBV co-infected, 56 (13%) with a previous AIDS diagnosis, 82 (19%) antiretroviral treatment naïve, 102 (24%) with HIV-RNA ≥50 cp/mL, CD4+=576 (437-749) cells/mm(3), nadir CD4+=308 (194-406) cells/mm(3). LSRs were observed in 70/565 (12.4%) treated syphilis. Incidence of LSR decreased over time [2004-2008 IR=25.1 (17.2-33.1)/1000 PMFU; 2009-2010 IR=21.1 (12.3-29.9)/1000 PMFU; 2011-2013 IR=10.6 (5.1-18.2)/1000 PMFU; Poisson regression: p=0.001]. RESULTS of univariate and multivariate analysis on the risk of LSR are reported in Table 1.


CONCLUSIONS
In HIV-infected subjects we observed 12% of LSR to treatment of syphilis. LSR was associated with an older age, late syphilis, lower nadir CD4+ and detectable HIV viral load.
Department of Infectious Diseases, IRCCS San Raffaele Hospital, Milan, Italy.
Vincenzo
V
Spagnuolo
Department of Infectious Diseases, IRCCS San Raffaele Hospital, Milan, Italy.
Andrea
A
Poli
Department of Infectious Diseases, IRCCS San Raffaele Hospital, Milan, Italy.
Laura
L
Galli
Department of Infectious Diseases, IRCCS San Raffaele Hospital, Milan, Italy.
Massimo
M
Cernuschi
Department of Infectious Diseases, IRCCS San Raffaele Hospital, Milan, Italy.
Silvia
S
Nozza
Department of Infectious Diseases, IRCCS San Raffaele Hospital, Milan, Italy.
Myriam
M
Maillard
Department of Infectious Diseases, IRCCS San Raffaele Hospital, Milan, Italy.
Nicola
N
Gianotti
Department of Infectious Diseases, IRCCS San Raffaele Hospital, Milan, Italy.
Hamid
H
Hasson
Department of Infectious Diseases, IRCCS San Raffaele Hospital, Milan, Italy.
Simona
S
Bossolasco
Department of Infectious Diseases, IRCCS San Raffaele Hospital, Milan, Italy.
Adriano
A
Lazzarin
Department of Infectious Diseases, IRCCS San Raffaele Hospital, Milan, Italy.
Antonella
A
Castagna