Dr. Joan A. Phelan, Professor and Chairperson of the Department of Oral Pathology and Director of the Diagnostic Pathology Laboratory, Division of Biological Science, Medicine, and Surgery.

Antiretroviral Therapy Use Among WIHS HIV+

A young HIV-infected woman with candidiasis, xerostomia, and enlarged salivary glands anxiously awaits a decision on her treatment.

Her dentist’s course of action depends on the answers to several complex questions: Are candidiasis and xerostomia a result of the patient’s HIV infection, or a side effect of the potent antiviral drugs she is taking? Will her salivary glands continue to grow if her viral load increases? And what new oral health problems will she face should her antiretroviral drug cocktail become ineffective?

As an investigator on an NIH/ NIDCR grant (the NIDCR-supported oral health substudy of the NIH- supported Women’s Interagency HIV Study [WIHS]), I have been seeking answers to these and other questions for the past seven years. WIHS is the world’s largest, longest-running effort to compare the health of HIV-infected women with HIV-negative women. Over 1,500 women are enrolled in WIHS, which began in 1995 under the joint auspices of seven federal agencies, including the National Institute of Allergy and Infectious Diseases, the Centers for Disease Control and Prevention, and the National Institute of Dental and Craniofacial Research.

WIHS subjects are enrolled in one of six regional health consortia, four of which also conduct oral health substudies. NYUCD’s partners in the New York regional consortium are Bronx-Lebanon Hospital Center/Montefiore Medical Center, Beth Israel Medical Center, Mount Sinai Medical Center, and Wadsworth Laboratories.

Approximately 100 women participate in the NYUCD oral health substudy. The women receive biannual physical exams at one of the participating hospitals, followed by a separate oral health evaluation at NYUCD. The data from the physical and oral exams, combined with additional analysis of behavioral and lifestyle factors affecting the women’s health, are sent to a central data bank, where they are made available to investigators who analyze the data based on a wide range of factors. These include the entire spectrum and course of HIV infection, as well as treatment-related, endocrine, nutritional, health care utilization, socioeconomic, and behavioral risk factors. Accordingly, my team is in a privileged position to understand the changes that occur in the oral cavity of HIV-infected women, including the long-term changes caused by the widespread adoption of highly active, antiretroviral (HAART) therapy. WIHS participants began taking these multi-drug combinations in 1996, a year after the study began. Findings to date include the following:

• Oral candidiasis lesions occur in HIV-positive women with high viral loads and low CD4+ counts who smoke. Candidiasis prevalence decreases as a result of HAART therapy. Oral candidiasis is a very sensitive marker of immune deficiency in HIV infection. Because oral candidiasis can be an early sign of AIDS, oral health care providers who observe it should counsel their patients about the importance of HIV testing. But providers also need to evaluate the other potential causes of candidiasis, which include systemic diseases such as diabetes mellitus, local factors such as decreased salivary flow, and the use of certain medications such as antibiotics and corticosteroids.
• In the first multiyear study to examine caries progression in HIV-infected individuals, WIHS determined that HIV-infected women have significantly more caries than seronegative women. There are several possible reasons for the difference, including microbial changes and the use of medications that decrease salivary flow.
• HIV-positive women have higher rates of salivary gland disease, as measured by enlargement, tenderness, and absence of saliva, compared to seronegative women. In addition, enlargement and tenderness of some glands increase with higher viral loads.
• Xerostomia and salivary gland hypofunction appear to be significantly higher in HIV-positive women relative to a comparable group of at-risk seronegative women. Immunosuppression levels measured by CD4+ cell counts were found to be strongly associated with xerostomia and salivary gland hypofunction in these women.

The NIDCR is expected to fund the WIHS oral health substudy for at least another year. As the study progresses, I expect new insights to emerge that could ultimately guide the planning and allocation of health care resources for HIV-infected women. For example, the reappearance of oral lesions could signal a weakening of HAART therapy’s effectiveness and the need to adopt new HIV-treatment regimens. And since one-third of HIV-infected subjects in my study also are infected with the Hepatitis C virus (HCV), I hope to better understand how HIV and HCV interact to affect oral health.

I’m also optimistic that researchers abroad who are intrigued by our findings will want to collaborate with us on similar studies. Scientists in Puerto Rico and Poland have shown an interest in such collaborative studies. And this summer, Dr. Anthony T. Vernillo, a Professor of Oral Pathology at NYUCD, hopes to gauge interest in collaborative studies in Africa when he travels to Tanzania to present WIHS data to the African chapter of the International Association for Dental Research (IADR).