In addition, in analyses stratified by the initial viral load, of the 26 men who had detectable viral loads before syphilis infection, 13 (50%) had a higher viral load during syphilis infection than before infection, with 12 having an increase of at least 0.5 log10 RNA copies/ml. By contrast, of the 10 men who were on HAART and had undetectable HIV viral loads before syphilis infection, only two (20%) had detectable viral loads at the time of syphilis diagnosis.
However, among the 35 men who had ‘during-to-after’ data, viral loads did not significantly decrease after syphilis treatment overall (mean change −0.10) or in any of the subgroups (Table 1).
In an alternative set of analyses, we examined viral loads in 19 men who had ‘before', ‘during', and ‘after’ viral load data, of whom 12 (63%) had secondary syphilis, 13 (68%) had detectable viral loads before syphilis and 15 (79%) were on HAART. Among these 19 men, the mean changes in log10 RNA copies/ml were 0.10 for ‘before-to-during', −0.03 for ‘during-to-after', and 0.07 for ‘before-to-after’ comparisons (all P > 0.2).
Among the 31 men who had ‘before-to-during’ CD4 cell count data, the CD4 cell count decreased significantly during syphilis infection (mean change −62 cells/mm3). The decreases in CD4 cell count were predominately in men with secondary syphilis, and in men who were not receiving antiretroviral therapy (Table 1). Overall, CD4 cell counts increased but not significantly after syphilis treatment (mean +33 cells/mm3), but the increases were significant in men who had lower CD4 cell counts and those who were receiving HAART (Table 1). Furthermore, for a subset of 15 men who had CD4 cell count data for ‘before', ‘during', and ‘after', the mean difference ‘before-to-after’ was +6.5 cells/mm3 (P = 1.00).
Furthermore, using information on other STDs abstracted from medical records in Los Angeles and the San Francisco surveillance data, we identified that 19 out of 52 men had other STDs in addition to syphilis during the time period of analysis. The ‘before-to-during’ changes in HIV-RNA log10 copies/ml for 22 men who had no other recorded STDs were similar to those for all the men in our study (mean 0.22, P = 0.12).
Syphilis infection was associated with a significant increase in the plasma HIV viral load and a significant decrease in CD4 cell counts in HIV-infected men. Increases in the HIV viral load occurred predominately in men who had secondary syphilis, which is a more generalized form of disease that might lead to greater immune activation than primary syphilis [8–10]. In agreement with some other studies of HIV-infected patients with co-infections [8,10,15], we found no significant reduction in viral load by 3–6 months after syphilis treatment, which may be related to persistent immune activation, but cannot be explained by syphilis treatment failures in this patient population.
This exploratory retrospective case-series study utilized existing medical records and laboratory data. No systematic data for concurrent infections and immunizations (which may affect HIV viral load and CD4 cell counts) and only limited data on other STDs were available. Plasma HIV viral loads were measured by a variety of assays, and viral load and CD4 cell count measurements were sometimes missing at timepoints of interest. Only 19 out of 52 men in our study population had data for ‘before', ‘during’ and ‘after’ timepoints, therefore we cannot rule out the possibility of selection bias affecting our findings. In addition, because we studied men who were enrolled in HIV care programs, the results may not be generalizable to all HIV and syphilis-co-infected men. We may have failed to detect some significant changes in the HIV viral load and CD4 cell count in subgroup analyses because of the small sample size and low statistical power, whereas other significant changes might have arisen by chance alone. Finally, our exploratory study did not have a comparison group of HIV-positive men not infected with syphilis. Instead, we examined within-person changes in viral loads and CD4 cell counts, with each man serving as his own control. We acknowledge that, as a result of HIV disease progression, the reported ‘before-to-during’ changes in viral loads and CD4 cell counts associated with syphilis may be somewhat overestimated, whereas the ‘during-to-after’ changes may be attenuated [17,18]. Larger confirmatory studies of patients diagnosed with syphilis in HIV care with careful viral load monitoring over longer periods of time may be useful to verify these findings, but probably challenging to conduct.
In conclusion, syphilis infection in HIV-infected men was associated with a significant increase in the HIV viral load and a significant decrease in the CD4 cell count. Because of the overlap in risk behaviors that lead to HIV and syphilis infections, and because syphilis may enhance HIV transmission via the syphilitic ulcers and by raising the HIV viral load , integrated public health efforts to prevent new syphilis infections, and to identify and treat syphilis cases promptly, are warranted to reduce the spread of both diseases within affected communities.
The authors would like to thank Charlotte Kent, William Wong, Lisa Smith, Jan King, and Alan Greenberg for consultations in the study design phase; Robert Kohn for providing San Francisco syphilis surveillance data sets; and Stevie Forte for help in data collection. They also wish to thank the staff and the following institutions for assistance in identifying patients eligible for the study and orienting them to their medical records: Joseph Engelman and Louis Hernandez at the San Francisco City Clinic; Charles Farthing and Manny Samayoa at the AIDS Healthcare Foundation, and John Stansell at the San Francisco General Hospital.
The findings of this study were presented in part at the National HIV Prevention Conference in Atlanta, Georgia, July 2003 [abstract no T2-L204].
Sponsorship: The study was financially supported by the Centers for Disease Control and Prevention (CDC) as part of a collaboration with the San Francisco city and Los Angeles county health departments.
This study was conducted as part of a public health response to syphilis outbreaks in San Francisco and Los Angeles. As such it was classified as exempt from informed consent requirements by the CDC Institutional Review Board, in accordance with the human experimentation guidelines of the US Department of Health and Human Services.
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Keywords:© 2004 Lippincott Williams & Wilkins, Inc.
CD4 cell count; HIV; immune response; men who have sex with men; sexually transmitted disease; syphilis; viral load