Short Bites: Xerostomia in Patients Living with HIV
November 7, 2017
In the United States, it is estimated that 1.1 million people are living with HIV. Of those, 1 in 7 do not know they are infected.  The number of new HIV diagnoses fell 19% from 2005 to 2014. Because HIV testing has remained stable or increased in recent years, this decrease in diagnoses suggests a true decline in new infections. The statistics in the Southern United States are not as promising. In 2015, the South accounted for 52% of the 18,303 new AIDS diagnoses in the United States, followed by the Northeast 18%, the West 17%, and the Midwest 12%. In 2015, the rate of new AIDS diagnoses was 7.9 in the South, 5.9 in the Northeast, 4.1 in the West, and 3.4 in the Midwest. Of the 6,721 deaths attributed directly to HIV or AIDS in 2014, 53% were in the South, 19% were in the Northeast, 17% were in the West, and 11% were in the Midwest. 
Florida statistics are more alarming, being ranked 1st among the 50 states in the number of HIV diagnosis in 2015. This year the number of reported HIV cases in Florida has jumped 23 percent, the biggest increase in a continuing upward trend that began in 2012 after several years of decrease. The proportion of Floridians infected with the disease is at its highest in seven years. Increases in new infections are present in almost all counties of the state. A review of all counties in Florida shows that the highest new infection rates are in Miami-Dade County with 47%, followed by Broward 41.5%, Orange 35.5%, and Hillsborough 30%.
For the dental profession, the state statistics are of particular importance. In the absence of antiretroviral therapy (ART), oral manifestations are the earliest significant indicators of HIV infection. Oral lesions are common (30–80%) in patients infected by the HIV virus and may indicate an impairment in the patient's general health status.
With new advances in ART, clinical and epidemiological observations have shown a considerable decline in the morbidity of HIV-positive patients. There has been a significant shift in both the type and frequency of oral lesions present in patients living with HIV/AIDS (PLWHA). Patients on ART show a lower incidence of oral lesions including candidiasis, oral hairy leukoplakia, and Kaposi’s sarcoma.  The prevalence of oral lesions has decreased by more than 30% since advancements in ART.
However, there has been an increase in prevalence of caries and periodontal disease. This increase can most likely be attributed to significant findings of xerostomia in PLWHA. Xerostomia is the subjective complaint of oral dryness. This must be distinguished from salivary gland dysfunction which is an objective disease characterized by reduced salivary flow. Studies have shown that 40% or more of PLWHA experience major xerostomia during their disease. Studies of PLWHA with xerostomia show a frequently negative effect on their quality of life.
Symptoms of xerostomia include cracked peeled atrophic lips, glossitis (Figure 1), and pale dry buccal mucosa (figure 2). Xerostomia can lead to dysphagia, dysgeusia, oral pain of unknown origin, dental caries, oral infections, periodontal disease, angular cheilitis associated with candidiasis (Figure 3) and can affect the health-related quality of life. These features of xerostomia can lead to the inability of the patient to take necessary medications and can influence intake of proper nutrients, leading to malnutrition and a decline in overall health.
There are multiple causes of xerostomia from various mechanisms. For example, anticholinergic effects of many medications, alcohol and drug abuse, and damaging head and neck radiation can cause xerostomia. There are many comorbidities from HIV/AIDS such as cardiac disease, diabetes, and mental health disorders which occurs in PLWHA. As a result, many of the medications especially the antidepressants, anxiolytics, diuretics, and antihistamines being taken for these comorbidities lead to xerostomia.
There are still differing studies of the xerostomic effects of antiretroviral medications used to treat HIV. Antiretroviral drugs are now recommended for all patients with an HIV diagnosis regardless of their immune system status as ART enables the immune system and works to decrease the possibility of HIV transmission from one person to another.
There are currently six classes of drugs used to treat HIV infection which include nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase inhibitors (INSTIs), fusion inhibitors (FIs), and chemokine receptor antagonists (CCR5 antagonists). In most cases, combination therapy includes three drugs to reduce HIV viremia to below detectable levels. A review of current literature suggests a relationship between orofacial adverse reactions related to these drugs classes. In relation to xerostomia, both the NRTI’s and PI’s have the most significant the oral side effect of xerostomia. However, recent studies indicate HIV positive patients not on ART are more vulnerable to decreased salivary flow rates. In one study, ART did not affect xerostomia or salivary flow rates in the studied population group. While low CD4 counts (<200cells/mm3) have been attributed by many authors to being a significant risk factor for xerostomia and hypo-salivation, others did not find this correlation significant. , 
More significant in the era of ART is the increase in prevalence of salivary gland disease. Salivary gland disease can arise in 4% to 8% of adults and children with HIV. HIV salivary gland disease (HIV-SGD) is a distinct disorder characterized by persistent major salivary gland swelling and xerostomia. Most commonly affected is one or both parotid glands sometimes which will occur without xerostomia. In some cases, salivary gland enlargement may be the first clinical manifestation of HIV infection, but more often a sign of late HIV infection. The exact pathophysiology of HIV-SD, origins include lymphoepithelial lesions, cysts, intraglandular lymph nodes, and an inflammatory infiltrate similar to what is often observed in Sjogren’s, syndrome however with distinct histopathologic and serological differences. In the infiltrate, there are persistent circulating CD8+lymphocytosis and diffuse visceral CD8+ lymphocytic infiltration.
Inflammatory or infectious diseases are the second most common group of salivary gland disorders in HIV disease, followed by neoplastic lesions. Kaposi’s sarcoma can account for 10% of malignant salivary gland neoplasms in HIV disease.
Treatment of salivary gland enlargement in HIV remains non-specific but could include aspiration of cystic lesions, superficial parotidectomy to alleviate swelling, and external radiation therapy for benign parotid hypertrophy.
Reports of xerostomia, in PLWH, must be given careful consideration as the xerostomia most often reflects the adverse effect of ART and or HIV salivary gland disease. Patients must be advised of the risks of caries and gingival inflammation as well as the physiological effects of xerostomia. The goal for the patient is to alleviate the symptoms by increasing the intake of water, sugar-free gum or candies, salivary substitutes, or therapeutic management with cholinergic agents. Overlying these treatments must be a careful monitoring of oral hygiene and the use of prescription topical fluorides.
Mark Schweizer, DDS MPH is an Assistant Professor and Director of Development and Special Projects, and Program Director for Ryan White HIV Programs at Nova Southeastern University College of Dental Medicine. Dr. Schweizer is also Dental Director for the Southeast AIDS Education and Training Center
George Kolos, DMD is an Assistant Professor at Nova Southeastern College of Dental Medicine. Dr. Kolos is a Florida Dental Association Trustee and a member of the International College of Dentists.