Antiretroviral use may improve syphilis treatment outcomes in coinfected people

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People with HIV who are taking antiretroviral therapy are less likely to experience the failure of syphilis treatment and less likely to develop neurosyphilis, according to two recently published studies.

An observational cohort study in the July 15th edition of Clinical Infectious Diseases found that HIV-positive people taking antiretroviral therapy had a lower syphilis serologic failure rate than those not taking antiretroviral therapy. The June 19th edition of AIDS reported on another study examining neurosyphilis in a subset of the same cohort; the results suggested that HIV-positive people who are taking antiretroviral therapy at the time of infection with syphilis may have lower odds of developing neurosyphilis than those who are not.

An important implication of both studies is that effective management of HIV infection in people who are coinfected with syphilis may increase the likelihood of successful syphilis treatment outcomes. Syphilis treatment was up to six times more likely to fail in HIV-positive people in the Johns Hopkins HIV Clinical Cohort, according to a previously reported study.

Glossary

syphilis

A sexually transmitted infection caused by the bacterium Treponema pallidum. Transmission can occur by direct contact with a syphilis sore during vaginal, anal, or oral sex. Sores may be found around the penis, vagina, or anus, or in the rectum, on the lips, or in the mouth, but syphilis is often asymptomatic. It can spread from an infected mother to her unborn baby.

treatment failure

Inability of a medical therapy to achieve the desired results. 

hazard

Expresses the risk that, during one very short moment in time, a person will experience an event, given that they have not already done so.

odds ratio (OR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 

hazard ratio

Comparing one group with another, expresses differences in the risk of something happening. A hazard ratio above 1 means the risk is higher in the group of interest; a hazard ratio below 1 means the risk is lower. Similar to ‘relative risk’.

Syphilis is a bacterial infection that is transmitted through genital sores or through rashes or lesions elsewhere on the body. Transmission also occurs through contact with infected blood and during pregnancy. Left untreated, syphilis can severely damage the brain, eyes, heart and other organs, and can be passed on to an unborn child and to sexual partners..

In HIV-positive people, untreated syphilis has a detrimental effect on CD4 cell counts and viral loads. Also, the sores caused by syphilis facilitate the transmission of HIV (Zetola, 2007).

An inexpensive serology test is commonly used to diagnose syphilis by identifying syphilis antibodies, and follow-up serology tests measure the effectiveness of treatment. Syphilis usually responds well to penicillin, the standard treatment, but not always. Treatment failure is defined as either the persistence of symptoms or the persistence of a high level of disease activity as measured by serologic findings. In cases of treatment failure, medical guidelines call for retreatment.

The studies in Clinical Infectious Diseases and AIDS utilized data from the Johns Hopkins HIV Clinical Cohort, which is comprised of HIV-positive patients at a large US medical center. The broader study analysed 231 cases of syphilis experienced by 180 people between 1990 and 2006. It identified 71 instances of serologic failure among 56 study participants. (Eleven people had two failures each, and two had three failures each.)

People whose CD4 cell counts were below 200 cells/mm3 at the time of the syphilis diagnosis were almost 2.5 times more likely to have serologic failure (adjusted hazard ratio, 2.48; 95% confidence interval, 1.26 – 4.88). Also, people using antiretroviral therapy were 60% less likely to have serologic failure (AHR, 0.40; 95% CI, 0.21 – 0.75). There was no association between HIV viral load level and serologic failure.

The researchers reported that 80 of the 180 participants took macrolide antibiotics, the majority as prophylaxis for opportunistic infections; the most common regimen was 1200 mg of azithromycin weekly. Among people with CD4 cell counts of 200 cells/mm3 or below, the use of macrolides was associated with a significant reduction in the serologic failure rate (hazard ratio, 0.53; 95% confidence interval, 0.36 – 0.79). Macrolide use also was significantly associated with syphilis seroreversion, which occurred in 29 people.

The authors conclude, “The interaction between syphilis and HIV infection is complex. In the future, a better understanding of the relationship between syphilis serologies and host immunity may help determine whether current treatment targets should be modified.”

The study appearing in AIDS identified 41 cases of neurosyphilis from among the 231 cases of syphilis discussed earlier. Neurosyphilis, which can be asymptomatic, occurs when syphilis bacteria penetrate the central nervous system.

People who had CD4 cell counts of less than 350 cells/mm3 were found to be at higher risk of developing neurosyphilis (odds ratio 2.87; 95% confidence interval: 1.18 – 7.02).

People who were using antiretroviral therapy prior to syphilis infection were 65% less likely to develop neurosyphilis (odds ratio 0.35; 95% confidence interval: 0.14 – 0.91). The use of antiretroviral therapy subsequent to treatment of neurosyphilis was also associated with less syphilis serologic failure, although not at a statistically significant level.

In about two-thirds of the 41 cases of neurosyphilis, patients reported symptoms. The most common symptoms were uveitis (a type of eye inflammation), altered cognition, motor weakness, headaches and gait abnormality. In the 14 cases of asymptomatic neurosyphilis, the diagnosis was made on the basis of lumbar puncture findings.

One-year follow-up information was available in 37 of the 41 cases. Follow-up lumbar punctures were performed in 16 of those cases, with most results showing either the resolution of cerebrospinal fluid abnormalities or improved parameters. However, in 12 of the 41 cases, either serologic failure or the persistence of syphilis symptoms led managing clinicians to call for retreatment, with a median time to retreatment of 536 days.

The authors suggest that the study results “highlight the importance of the immune response in controlling syphilis and the possible role of [antiretroviral therapy] in mitigating neurological complications of syphilis among coinfected patients.”

References

Ghanem KG et al. Antiretroviral therapy is associated with reduced serologic failure rates for syphilis among HIV-infected patients. Clin Infect Dis 47: 258 – 265, 2008.

Ghanem KG et al. Neurosyphilis in a clinical cohort of HIV-1-infected patients. AIDS 22: 1145 – 1151, 2008.

Zetola NM et al. Syphilis and HIV infection: an update. Clin Infect Dis 44: 1222 – 1228, 2007.