Oral Human Immunodeficiency Virus Research Articles

Human Immunodeficiency Virus Prevalence Is Increasing Among Men Who Have Sex With Men in China: Findings From a Review and Meta-Analysis

Multiple studies reported a fast-spreading human immunodeficiency virus (HIV) epidemic among men who have sex with men (MSM) in China. This study aimed to estimate the magnitude and time trends of HIV prevalence among MSM in different geographical regions of China through a systemic review and meta-analysis. A total of 94 articles were identified (25 in English and 69 in Chinese) and analyzed. National HIV prevalence among Chinese MSM has increased over this period, from 1.4% (95% confidence interval [CI]: 0.8%-2.4%) in 2001 to 5.3% (95% CI: 4.8%-5.8%) in 2009. MSM in Southwest China have the highest HIV prevalence, of 11.4% (95% CI: 9.6%-13.5%) in comparison with other regions, which range 3.5% to 4.8%. Significant increases in HIV prevalence among MSM were consistently observed across all Chinese regions. There is an urgent need for implementation of effective public health interventions to curb the spread of HIV infection among MSM across China, especially in the Southwest.

Knowledge and attitude regarding human immunodeficiency virus/acquired immunodeficiency syndrome in dermatological outpatients

Dermatologists are often the first-line specialists who recognize and diagnose human immunodeficiency virus (HIV) infection because of pathognomic skin signs. It is therefore important to investigate attitudes and knowledge regarding HIV/acquired immunodeficiency syndrome (AIDS) amongst dermatological patients in order to provide information for dermatologists and to draw their attention to the issues. Awareness of HIV/AIDS, its prevention, and hypothetical behaviour were surveyed in dermatological outpatients. The anonymous cross-sectional survey was conducted with consecutive German-speaking outpatients aged 18-65 years, who registered at the dermatological outpatient's clinic (excluding venereology, genitourinary or HIV medicine) of the University of Munich (Germany). Three hundred forty-seven (77.5%) questionnaires were accepted for analysis. Most of the patients knew about HIV incurability (89.4%), HIV transmissibility during needle sharing (95.3%), or vaginal (87.4%) and anal intercourse (79.5%), as well as about HIV prevention by condom use (97.8%), and use of single needles (76.2%). However, knowledge gaps and misconceptions were detected regarding the risk of HIV transmission during oral sex, and the efficacy of sexual fidelity and avoidance of blood transfusions in HIV prevention. The lowest knowledge level (< 50% correct answers) was detected in patients aged 50-59 years, in unemployed, divorced/widowed, and in those without or with incomplete school education. Patient education about HIV/AIDS in dermatological ambulant settings should be performed differentially with regard to socio-demographic factors, and focused on the topic of oral sexual HIV transmission and on some other specific misconceptions.

Snapshots for July 2007

Snapshots for July 2007

Oral complication risks after invasive and non‐invasive dental procedures in HIV‐positive patients

Limited published scientific evidence is available to provide guidance to clinicians on possible increased risks of invasive oral procedures associated with the human immunodeficiency virus (HIV) status of the patient. The aim of this study was to assess post-procedural complications in patients infected with HIV. This was a retrospective cross-sectional study of the records of 101 consecutive HIV patients treated at the School of Dentistry of Madrid Complutense University and Sandoval STD Clinic in Madrid between January 2003 and February 2005. Data were gathered by an experienced dental practitioner using a structured epidemiological questionnaire for information on gender, age, HIV transmission category, medical history, hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection and other diseases, TCD4+ and TCD8+ count, HIV viral load (VL), platelet count, neutrophil count, international normalized ratio and haemoglobin level; tobacco and alcohol intake, highly active antiretroviral treatment and presence of oral lesions. Information was also collected on complications related to dental treatment (invasive or non-invasive) during the previous 6 months. Chi-squared test and Fisher's exact test were used to establish statistical significance. Data were gathered on 314 dental procedures in 101 patients. The overall complication rate was 2.2% (7/314); in 147 invasive procedures, seven complications (4.8%) were documented (one persistent pain, two prolonged bleeding, three infections, one bone sequestrum) including extractions, periodontal scaling, endodontic treatment and biopsy. No differences were found in TCD4+, TCD8+, platelet count, HBV or HCV co-infections or HIV VL between patients with and/or without complications. Patients with complications were mainly in B stage of HIV disease (P=0.020). Oral lesions and smoking habit>20 cig day-1 were documented in 83.3% (P=0.086) and 50% (P=0.060), respectively, of patients with complications. The complication rate was 2.2% overall and 4.8% after invasive dental procedures. Presence of oral lesions, smoking habit or HIV clinical stage B may be predictive factors for oral complications in HIV patients. No relationship was found between complications and virological, immunological or other laboratory values. Studies with wider samples and negative control group are warranted to confirm the absence of an association between HIV positivity and higher risk of oral complications.

Snapshots for May 2006

Snapshots for May 2006

Human β-Defensins Suppress Human Immunodeficiency Virus Infection: Potential Role in Mucosal Protection

Beta-defensins are small (3 to 5 kDa in size) secreted antimicrobial and antiviral proteins that are components of innate immunity. Beta-defensins are secreted by epithelial cells, and they are expressed at high levels in several mucosae, including the mouth, where the concentration of these proteins can reach 100 microg/ml. Because of these properties, we wondered whether they could be part of the defenses that lower oral transmission of human immunodeficiency virus (HIV) compared to other mucosal sites. Our data show that select beta-defensins, especially human beta-defensin 2 (hBD2) and hBD3, inhibit R5 and X4 HIV infection in a dose-dependent manner at doses that are compatible with or below those measured in the oral cavity. We observed that beta-defensin treatment inhibited accumulation of early products of reverse transcription, as detected by PCR. We could not, however, detect any reproducible inhibition of env-mediated fusion, and we did not observe any modulation of HIV coreceptors following treatment with hBD1 and hBD2, in both resting and phytohemagglutinin-activated cells. Our data instead suggest that, besides a direct inactivation of HIV virions, hBD2 inhibits HIV replication in the intracellular environment. Therefore, we speculate that beta-defensins mediate a novel antiretroviral mechanism that contributes to prevention of oral HIV transmission in the oral cavity. Immunohistochemical data on hBD2 expression in oral mucosal tissue shows that hBD2 is constitutively expressed, forming a barrier layer across the epithelium in healthy subjects, while in HIV-positive subjects levels of hBD2 expression are dramatically diminished. This may predispose HIV-positive subjects to increased incidence of oral complications associated with HIV infection.

A Model System of Oral HIV Exposure, Using Human Palatine Tonsil, Reveals Extensive Binding of HIV Infectivity, with Limited Progression to Primary Infection

Oral exposure to human immunodeficiency virus (HIV) type 1 results in systemic infection, but many details surrounding virus transmission remain unresolved. We developed a mucosal model, using human palatine tonsil with intact external epithelium, to study events after oral exposure to HIV. When applied to the external epithelium, semen from an HIV-seropositive patient and cell-free virus both established HIV infection in individual tonsillar cells. However, clusters of infected tonsillar cells were detected where the epithelial surface was damaged. Investigation of the initial events in HIV transmission revealed extensive and stable binding of HIV virions and seminal cells to tonsil epithelium. In experiments modeling physiologically relevant events, the addition of seminal plasma resulted in enhanced virion binding to epithelial cells. These results indicate that, although extensive binding of HIV virions and seminal cells can be demonstrated at an exposed mucosal surface, there is only limited progression from binding to primary infection.

Self-reported oral dryness and HIV disease in a national sample of patients receiving medical care.

We sought to analyze the relationship between self-reported oral dryness and the demographic, enabling, behavioral, clinical, and treatment characteristics among human immunodeficiency virus (HIV)-positive patients in medical care. The study group consisted of the HIV Cost and Services Utilization Study cohort, a nationally representative probability sample of HIV-infected adults receiving medical care in the contiguous United States. It was estimated that 29% of adults (64,947 individuals) with HIV infection receiving medical care in the United States have a complaint of dry mouth. A multivariate logistic analysis was carried out to explore the association between several covariates and dry mouth. It was shown that compared with whites, individuals of Hispanic ethnic origin were 61% more likely to report dry mouth (OR, 1.61; 95% CI, 1.04-2.50; P =.04). Those who were unemployed were 55% more likely to report the symptom of dry mouth than were subjects who were employed (OR, 1.55; 95% CI, 1.22-1.98; P =.001). In comparison with nonsmokers, current smokers were 36% more likely to report dry mouth (OR, 1.36; 95% CI, 1.04-1.79;P =.03). The use of antidepressant drugs and antituberculosis/anti-Mycobacterium avium (anti-TB/anti-MAC) medications had the strongest association with dry mouth complaint. Those taking antidepressants were 55% more likely to report dry mouth (OR, 1.55; 95% CI, 1.23-1.97; P =.0001); compared with nonusers, patients receiving anti-TB/MAC drugs were 46% more likely to report dry mouth (OR, 1.46; 95% CI, 1.03-2.06; P =.04]. In comparison with those with undetectable viral load, individuals with a viral load of more than 100,000/mm(3) were 151% more likely to report dry mouth (OR, 2.51; 95% CI,1.58-3.96; P =.0001). Our findings suggest that optimizing viral suppression, smoking cessation, and tailoring antidepressant and anti-TB/MAC medications may be promising interventions to decrease dry-mouth symptoms among HIV-infected individuals.

Oral absorption of the HIV protease inhibitors: a current update

Although the human immunodeficiency virus (HIV) protease inhibitors are highly effective, they are characterized by low and/or variable bioavailability with limited penetration into the central nervous system (CNS). Their clinical use is limited by patient compliance and by drug–drug interactions. The effect of drug solubility on their oral absorption has been investigated but further evaluation of this relationship is required. First pass metabolism appears to be significant for the HIV protease inhibitors and they are extensively metabolized by cytochrome P450 (CYP) 3A4. Recent studies suggest that these drugs are substrates for the P-glycoprotein efflux pump, which can limit their intestinal absorption and their transport across the blood–brain barrier. Drugs inducing or inhibiting CYP3A4 and/or P-glycoprotein may influence the bioavailability of the HIV protease inhibitors. The low bioavailability, variable absorption and drug–drug interactions of the HIV protease inhibitors may be related to the variability of cytochrome P450 and P-glycoprotein expression and to possible CYP3A4/P-glycoprotein interactions. To improve oral HIV protease inhibitor therapy, it is essential to mechanistically characterize the cell specific, tissue specific and regional intestinal dependencies of drug transport, secretory transport, metabolism and P-glycoprotein/CPY3A4 interactions. This report reviews the physicochemical characteristics and pharmacokinetics of the HIV protease inhibitors while considering the relationships between their hepatic and intestinal metabolism, low bioavailability, variable absorption and drug–drug interactions.

Why is HIV rarely transmitted by oral secretions? Saliva can disrupt orally shed, infected leukocytes.

Oral transmission of human immunodeficiency virus (HIV) by the millions of HIV-infected individuals is a rare event, even when infected blood and exudate is present. Saliva of viremic individuals usually contains only noninfectious components of HIV indicating virus breakdown. To determine whether unknown HIV inhibitory mechanisms may explain the almost complete absence of infectious HIV in the saliva. Since most of the infectious HIV that is shed mucosally by asymptomatic individuals is found in, produced by, and transmitted by infected mononuclear leukocytes, we determined whether saliva, which is hypotonic, may disrupt these infected cells, thereby preventing virus multiplication and cell-to-cell transmission of HIV. Specifically, we measured (1) whether mononuclear leukocytes were lysed by saliva and (2) whether the lysis by saliva inhibits the multiplication of HIV and other viruses in infected leukocytes and other cells. Saliva rapidly disrupted 90% or more of blood mononuclear leukocytes and other cultured cells. Concomitantly, there was a 10000-fold or higher inhibition of the multiplication of HIV and surrogate viruses. Further experiments indicated that the cell disruption is due to the hypotonicity of saliva: Hypotonic disruption may be a major mechanism by which saliva kills infected mononuclear leukocytes and prevents their attachment to mucosal epithelial cells and production of infectious HIV, thereby preventing transmission. Implications for the known oral HIV transmission by milk and seminal fluid, as well as potential oral transmission to contacts and health care workers, are considered. This effective salivary defense may be applicable medically to interdict vaginal, rectal, and oral transmission of HIV by infected cells in seminal fluid or milk by the use of anticellular substances.

The acceptability of oral fluid testing for HIV antibodies. A pilot study in gay bars in a predominantly rural state.

One barrier for individuals desiring human immunodeficiency virus (HIV) antibody testing has been the lack of alternatives to blood HIV testing. Oral fluid HIV testing provides another testing option. To evaluate the acceptability of oral fluid testing for HIV antibodies in a gay bar outreach setting. This pilot study was conducted using the HIV Risk Behavior Survey (HRBS) and OraSure acceptability survey in gay bars in Columbia, South Carolina during July and August, 1997. Of the 118 HRBS participants, 54% agreed to take the oral fluid test with 6% testing positive. A majority (91%) of participants felt comfortable with the oral HIV antibody testing in gay bars. Also, 21.8% of individuals in the OraSure study were tested for the first time. This study indicates that oral fluid testing for HIV antibodies in an outreach setting is acceptable and effective in reaching individuals who do not usually access traditional testing sites.

Oral Diagnostic Testing for Detecting Human Immunodeficiency Virus-1 Antibodies: A Technology Whose Time Has Come

An oral fluid-based test for antibodies to human immunodeficiency virus (HIV), equivalent to serum in its accuracy but safer and easier to use, is now available in the United States. The development of the oral test involved overcoming technical obstacles to the use of oral fluid as a testing medium, including low immunoglobulin G (IgG) titers, suboptimal assay performance, protease degradation of IgG, high viscosity, and lack of a standardized method of specimen collection, all of which contribute to suboptimal assay performance. The currently available oral HIV test utilizes a collection device to isolate a mucosal transudate component of oral fluid rich in IgG. A vial containing a preservative solution facilitates the transport of stable, low-viscosity specimens to the laboratory for testing with an ELISA and confirmatory Western blot assay, specifically designed for use with oral fluid. Non-HIV medical conditions and oral pathologies do not appear to affect oral test results. Hopefully, the availability of a more patient-friendly, portable diagnostic test for antibodies to HIV will facilitate identification of greater numbers of infected individuals with the ultimate goals of early identification, early treatment, and prevention of disease transmission.

Oral immunization with recombinant Mycobacterium bovis BCG simian immunodeficiency virus nef induces local and systemic cytotoxic T-lymphocyte responses in mice.

Recombinant live Mycobacterium bovis BCG vectors (rBCG) induce strong cellular and humoral immune responses against various antigens after either systemic or oral immunization of mice. Cytotoxic T-lymphocyte (CTL) responses may contribute to the control of human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) infections whose portal of entry is the gastrointestinal or genital mucosa. In this study, we immunized BALB/c mice with a recombinant BCG SIV nef and observed its behavior in oropharyngeal and target organ lymphoid tissues. The cellular immune responses, particularly the intestinal intraepithelial and systemic CTL responses, were investigated. The results showed that rBCG SIV nef translocated the oropharyngeal mucosa and intestinal epithelium. It diffused to and persisted in target lymphoid organs. Specific SIV Nef peptide proliferative responses and cytokine production were observed. Strong systemic and mucosal CTL responses were induced. In particular, we demonstrated direct specific anti-Nef CTL in intestinal intraepithelial CD8beta+ T cells. These findings provide evidence that orally administered rBCG SIV nef may contribute to local defenses against viral invasion. Therefore, rBCG SIV nef could be a candidate vaccine to protect against SIV infection and may be used to develop an oral rBCG HIV nef vaccine.