Chemoprophylaxis for HIV prevention: new opportunities and new questions

Growing data suggest that antiretrovirals can be used as an effective means of HIV prevention. This article reviews the current status and future clinical prospects of utilizing antiretroviral chemoprophylaxis before and after high-risk HIV exposure to prevent HIV transmission. The discussion about using antiretrovirals as a means of primary HIV prevention has moved to the forefront of public health discourse because of a growing evidence base, the increased tolerability of the medications, the decreased cost, the ever-expanding formulary, and the limitations of other approaches.     

DNA vaccines for HIV: challenges and opportunities

In December 2005, the UNAIDS and WHO reported that the global epidemic known as acquired immunodeficiency syndrome (AIDS) has claimed the lives of more than 25 million adults and children over the past 26 years. These figures included an estimated 3.1 million AIDS-related deaths in 2005. Despite enormous efforts to control the spread of human immunodeficiency virus (HIV) new infection rates are on the rise. An estimated 40.3 million people are now living with HIV, including 4.9 million new infections this past year. Nearly half of new HIV infections are in young people between the ages of 15 and 24. While drug therapies have helped sustain the lives of infected individuals in wealthy regions, they are relatively unavailable to the poorest global regions. This includes sub-Saharan Africa which has ∼25.8 million infected individuals, more than triple the number of infections of any other region in the world. It is widely believed that the greatest hope for controlling this devastating pandemic is a vaccine. In this review, we will discuss the current state of DNA-based vaccines and how they compare to other vaccination methods currently under investigation. We will also discuss innovative ideas for enhancing DNA vaccine efficacy and the progress being made toward developing an effective vaccine.     

Case-control study of risk factors for incident HIV infection in rural Uganda

OBJECTIVE: To identify risk factors associated with HIV incidence in a rural Ugandan population. DESIGN: Case-control study. METHODS: Men and women who seroconverted between 1990 and 1997 (cases) and seronegative subjects (controls) were drawn from a general population cohort of approximately 5000 adults in rural, southwestern Uganda. Information on risk factors was ascertained through a detailed interview and physical examination by clinicians who were blind to the study subjects' HIV status. All patients were interviewed within 2 years of their estimated date of seroconversion. RESULTS: Data were available on 130 men (37 cases, 93 controls) and 133 women (46 cases, 87 controls). There was a significantly higher risk of infection in men (odds ratio [OR], 6.51; 95% confidence interval [CI], 1.06-39.84) and women (OR, 4.75; 95% CI, 1.26-17.9) who were unmarried and in a steady relationship, and in men who were divorced, separated, or widowed (OR, 4.33; 95% CI, 1.32-14.25) compared with those who were married. There was a significantly higher risk of HIV infection in men (OR, 3.78; 95% CI, 1.20-11.93) and women (OR, 20.78; 95% CI, 2.94-141.2) who reported > or =5 lifetime sexual partners compared with those who reported at most 1 partner. For men, there was an increased risk of infection associated with receiving increasing numbers of injections in the 6 months prior to interview (p < .001 for trend). Women reporting sex against their will in the year prior to interview were at higher risk of infection (OR, 7.84; 95% CI, 1.29-47.86; p = .020). CONCLUSIONS: The strongest risk factor for HIV incidence in this rural Ugandan population is lifetime sexual partners. The increased risks found for women reporting coercive sex and men reporting injections require further investigation.     

Risk factors for incident HIV infection among anonymous HIV testing site clients in Santos,Brazil: 1996-1999

OBJECTIVES: To determine temporal trends in HIV infection and risk factors among persons seeking anonymous HIV testing in Santos, Brazil. METHODS: Data and sera from persons testing for HIV from 1996 to 1999 were used. Exposures were abstracted from HIV testing risk assessments. Stored HIV-positive sera were tested to identify recently acquired HIV infection using a serologic testing algorithm for detecting recent HIV seroconversion (STARHS). Independent associations between exposures and recently acquired HIV infection were determined using multivariate analyses. RESULTS: Overall, estimated HIV incidence was 2.0% (95% CI: 1.1-3.5) for the 4-year period: 1.2% (95% CI: 0.5-2.6) in women and 2.7% (95% CI: 1.3-5.0) in men. Incidence increased among women but remained stable among men. Exposures independently associated with incident infection included a history of sex work (OR= 5.4, 95% CI: 1.5-18.7), concurrent syphilis infection (OR =4.1, 95% CI: 1.4-11.9), anal sex (OR = 3.0, 95% CI: 1.3-7.1), and having an HIV-positive sexual partner (OR= 1.4, 95% CI: 1.1-1.9). CONCLUSIONS: This study further demonstrates the public health utility of using the STARHS for the assessment of emerging trends in the HIV epidemic. Results from this study will help to target appropriate prevention strategies directed toward at-risk populations in Santos.     

Requiring help injecting independently predicts incident HIV infection among injection drug users

BACKGROUND: Requiring help injecting has been associated with syringe sharing among injection drug users (IDUs). No prospective study has fully examined this risk factor and its relation to rates of HIV infection. We investigated whether requiring help injecting illicit drugs was a predictor of HIV infection among a prospective cohort of IDUs. METHODS: The Vancouver Injection Drug User Study is a prospective study of more than 1500 IDUs who have been recruited from the Downtown Eastside of Vancouver since May 1996. At baseline and semiannually, subjects provided blood samples and completed an interviewer-administered questionnaire. The questionnaire elicits demographic data as well as information about drug use, HIV risk behavior, and drug treatment. HIV incidence rates were calculated using Kaplan-Meier methods, and Cox regression determined independent predictors of seroconversion. RESULTS: A total of 1013 baseline HIV-negative participants were eligible for this study. Within this population, 418 (41.3%) participants had required help injecting during the last 6 months at baseline. Participants requiring help injecting were more likely to be female (odds ratio = 2.3, 95% confidence interval [CI]: 1.8-3.0; P < 0.001), were slightly younger (33.5 vs. 34.9 years of age; P = 0.014), and had fewer years of experience injecting drugs (7 vs. 11 years; P < or = 0.001). Among participants who required help injecting at baseline, cumulative HIV incidence at 36 months was 16.1% compared with 8.8% among participants who did not require help injecting (log-rank, P < 0.001). In an adjusted model controlling for potential confounding variables, being aboriginal (relative hazard [RH] = 1.68, 95% CI: 1.15-2.48), injecting cocaine daily (RH = 2.71, 95% CI: 1.87-3.95), and requiring help injecting (RH = 1.79, 95% CI: 1.23-2.62) remained independent predictors of HIV seroconversion. CONCLUSIONS: These data demonstrate the need for interventions to reduce the risk of HIV infection among IDUs who require help injecting.     

Voluntary counseling, testing, and referral for HIV: new technologies, research findings create dynamic opportunities

Programs for voluntary counseling and testing (VCT) for HIV play an increasingly important role in comprehensive prevention and care strategies. New technological advancements and behavioral interventions can improve the effectiveness of VCT as a tool for preventing new HIV infections and helping HIV-positive individuals access appropriate care. With growing consensus that early access to HIV therapy increases its effectiveness, and that individuals diagnosed with HIV reduce risk behavior, VCT has become integral to the continuum of HIV primary care. However, federal funding of VCT has declined, with concomitant decreases in numbers of people being tested. An estimated 200,000 people in the United States remain unaware that they are HIV positive, and many at-risk individuals do not seek out standard HIV counseling and testing services. To increase the acceptability and effectiveness of VCT, the authors recommend that VCT programs employ outreach programs offering anonymous testing to reach those at heightened risk of HIV infection, and to make rapid use of new technologies and counseling strategies to improve the reach and efficacy. Given the important role that VCT can play in both prevention and early treatment, the authors recommend significant increases in federal support.     

Atopic dermatitis: new insights and opportunities for therapeutic intervention

Atopic dermatitis (AD) is a chronic inflammatory skin disease that frequently predates the development of allergic rhinitis or asthma. It is an important skin condition with significant costs and morbidity to patients and their families; the disease affects more than 10% of children. Recent studies have demonstrated the complex interrelationship of genetic, environmental, skin barrier, pharmacologic, psychologic, and immunologic factors that contribute to the development and severity of AD. The current review will examine the cellular and molecular mechanisms that contribute to AD as well as the immunologic triggers involved in its pathogenesis. These insights provide new opportunities for therapeutic intervention in this common skin condition.     

Environmental pathology: new directions and opportunities

The National Institute of Environmental Health Sciences (NIEHS) supports a number of training programs for predoctoral and postdoctoral (D.V.M., M.D., Ph.D.) fellows in toxicology, epidemiology and biostatistics, and environmental pathology. At the Experimental Biology meeting in April 1997, the American Society of Investigative Pathology (ASIP) sponsored a workshop including directors, trainees, and other interested scientists from several environmental pathology programs in medical and veterinary colleges. This workshop and a related session on "Novel Cell Imaging Techniques for Detection of Cell Injury" revealed advances in molecular and cell imaging approaches as reviewed below that have a wide applicability to toxicologic pathology.     

AIDS-free survival and overall survival in HIV infection: the new CDC classification system (1993) for HIV disease and AIDS

The clinical history of 1538 HIV positive patients was analyzed on the basis of the new CDC classification system of HIV disease and AIDS. This classification system combines three CD4 cell categories (1, 2, and 3) with three clinical categories (A, B, and C) into nine subgroups AI–C3. We examined the overall survival for all subgroups and the AIDS-free survival for subgroups Al–B3. AIDS-free survival for patients in subgroups Al, A2, and B1 was considerably longer than survival in patients from subgroups A3, B2, and B3 (P < 0.0001). According to these findings, the new CDC classification system could be simplified into three stages, stage I and II comprising the above mentioned six subgroups, and stage III comprising clinical AIDS defining categories C1, C2, and C3. These three stages correspond to different periods in the management of HIV positive patients, i.e., period of observation, period of prophylaxis, and period of treatment.Abbreviations AIDS acquired immunodeficiency syndrome - CDC Centers for Disease Control - HIV Human immunodeficiency virus Correspondence to: E.B. Helm