Dissertation/Thesis Abstract

Syphilis as an opportunistic infection in HIV
by Ghanem, Khalil G., Ph.D., The Johns Hopkins University, 2009, 144; 3357182
Abstract (Summary)

Human immunodeficiency virus (HIV) infection and syphilis frequently co-exist but the impact that each infection has on the other is incompletely understood. This dissertation describes three epidemiologic studies conducted in two separate cohorts of HIV and syphilis co-infected patients in Baltimore, Maryland. The goals of these studies are to: (1) Compare the serologic response to syphilis therapy in HIV-infected patients vs. HIV-uninfected patients. (2) Describe the impact of HIV-induced immunosuppression, and its reversal with the use of highly active antiretroviral therapy (HAART), on the course of syphilis and its neurologic complications.

In the first study, we compare treatment follow-up and syphilis serological response rates following standard syphilis therapeutic regimens between HIV infected (N=129) and uninfected (N=168) patients with early and late latent stages of syphilis attending the two Baltimore City Health Department Sexually Transmitted Diseases Clinics. We found that 64% of HIV infected patients did not have documented follow-up serologies; among those who did follow-up, there was an increased risk of serological failure among the HIV+ group [adjusted hazards ratio (aHR) 6.0, 95%CI: 1.5-23.9; p=0.01].

In the second study, we evaluate the role of immunosuppression, and its reversal using HAART, on the course of syphilis in a dynamic cohort of HIV positive patients receiving care at a university-based clinic in Baltimore between 1990 and 2006. During a median follow-up time of 5.3 years, we found that among 231 incident syphilis cases, a CD4 cell count of <200 cells/ml at the time of syphilis diagnosis increased the risk of serological failure (aHR 2.48; 95% CI: 1.26-4.88). The use of HAART was associated with a 60% (0.40; CI: 0.21-0.75) reduction in serologic failures independent of concomitant CD4 cell response, and an 82% (0.18; 0.05-0.52) reduction among those who experienced a >50% increase in CD4 cells over baseline. Similarly, the use of macrolides as opportunistic infection prophylaxis for >3 months during follow-up decreased serologic failures by 41% (0.59; 0.43-0.82). RPR seroreversion was infrequent (16.1%), inconsistent, and more likely to occur among patients receiving macrolides.

In the last study, we describe the risk factors for neurosyphilis in the same cohort of HIV-infected patients and assess the effect of immunosuppression on therapeutic response to standard therapy. We found that risk factors for neurosyphilis among HIV-1 infected patients included a CD4 cell count of ≤350 cells/ml at the time of syphilis diagnosis [adjusted odds ratio (aOR):2.87; 1.18-7.02]. Use of any HAART prior to syphilis infection reduced the odds of neurosyphilis by 65% (0.35; 0.14-0.91, p=0.03). Follow-up lumbar puncture within 12 months revealed only 37.5% had resolution of all CSF abnormalities. At 1 year, 38% had persistence of their major neurologic symptom despite adequate treatment for neurosyphilis.

The current CDC recommendation for more aggressive serologic follow-up of HIV-infected patients is not being met. However, aggressive reversal of immunosuppression using HAART, and the use of macrolides for opportunistic infection prophylaxis appear to be effective at decreasing syphilis serologic failures and neurologic complications. These findings suggest that syphilis acts as an opportunistic infection in HIV infection.

Indexing (document details)
School: The Johns Hopkins University
School Location: United States -- Maryland
Source: DAI-B 70/04, Dissertation Abstracts International
Subjects: Epidemiology
Keywords: HAART, HIV, Neurosyphilis, Opportunistic infections, Syphilis
Publication Number: 3357182
ISBN: 9781109138672
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