Working Toward an AIDS-Free Generation



Ending the global HIV/AIDS pandemic may be possible by implementing a multifaceted global effort that expands testing, treatment, and prevention programs, as well as meets the scientific challenges of developing an HIV vaccine and possibly a cure, according to a Viewpoint in the July 25 issue of JAMA, a theme issue on HIV/AIDS.

Anthony S. Fauci, M.D., Director, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, Md., presented the article at a JAMA media briefing at the International AIDS Conference.

Dr. Fauci and co-author Gregory K. Folkers, M.S., M.P.H., also of the NIAID, write that “since the first cases of what is now known as AIDS were reported in 1981, an entire generation has grown up under the constant cloud of this modern-day plague. Across the globe, more than 34 million people are living with the human immunodeficiency virus (HIV), the virus that causes AIDS, including approximately 1.2 million individuals in the United States. HIV/AIDS has been responsible for the deaths of an estimated 30 million individuals.” They add that although the rate of new HIV infections has declined or stabilized in many countries, the disease continues to exact an enormous toll: 1.8 million deaths in 2010 alone, and grief and hardship for countless families and communities.

Because powerful interventions have been developed and scientifically proven effective, the fight against HIV/AIDS is currently viewed with considerably more optimism than in past years, the authors write. “If these tools are made widely available to those who need them, an AIDS-free generation may be possible—that is, today's children could one day live in a world in which HIV infections and deaths from AIDS are rare.”

Among the most important interventions is combination antiretroviral therapy, which significantly improves the health and longevity of individuals infected with HIV. “Since the advent of antiretroviral therapy, the annual number of deaths due to AIDS has decreased by two-thirds in the United States. Globally, an estimated 700,000 lives were saved in 2010 alone due to the increased availability of antiretroviral therapy in low- and middle-income countries,” the authors write. “Important challenges remain—notably finding the resources and developing the infrastructure to provide antiretroviral therapy to the estimated 8 million individuals with HIV infection who need these drugs but are not receiving them.”

The authors add that antiretroviral therapy can also prevent HIV infection by reducing the amount of virus in an infected person's blood and other body fluids, making it less likely that the virus will be transmitted to others. Also, antiretroviral therapy is highly effective in blocking mother-to-child HIV transmission.

Other important interventions include medical male circumcision, which offers a highly effective and durable way to protect heterosexual men from HIV infection; and potentially, pre-exposure prophylaxis with antiretroviral medications, which have shown promise in reducing an individual's risk of acquiring HIV infection.

“Each of these treatment and prevention strategies has a strong evidence base; with further refinement and scale-up and also when used in combination, they could have an extraordinary effect on decreasing the trajectory of the HIV pandemic.”

According to the authors, researchers are maintaining focus on 2 key scientific challenges that remain: the development of a vaccine and a cure. They write that modest success in a large-scale clinical trial of an HIV vaccine, promising results in animal models, and advances in structure-based vaccine design suggest that an HIV vaccine is feasible. The prospect of an HIV cure remains challenging.

The authors conclude that ending the global HIV/AIDS pandemic “will require a global commitment of resources involving additional donor countries, strengthening health care systems overall, and fostering greater ownership by host countries of HIV/AIDS effort, including investing more in the health of their people. With collective and resolute action now and a steadfast commitment for years to come, an AIDS-free generation is indeed within reach.”

(JAMA. 2012;308[4]:343-344.


Use of Hydroxychloroquine Does Not Slow HIV Disease Progression Among Patients Not Taking Antiretroviral Therapy


Nicholas I. Paton, M.D., F.R.C.P., of the MRC Clinical Trials Unit, London, and colleagues conducted a study to examine whether hydroxychloroquine decreases immune activation and inflammation and subsequently slows the progression of early HIV disease. Hydroxychloroquine is a drug that has immunomodulatory and anti-inflammatory properties and has been reported to have anti-HIV properties in vitro.

“International HIV treatment guidelines recommend that antiretroviral therapy should be started when the CD4 cell count reaches 350 cells/µL, but resource limitations prevent implementation of this recommendation in many countries. An inexpensive, safe, and well-tolerated intervention that slowed the rate of decline of CD4 cells (and thereby delayed the time of starting combination antiretroviral therapy) would therefore be attractive,” according to background information in the article.

The randomized, placebo-controlled trial was performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/µL. Patients received hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks.

The researchers found that “hydroxychloroquine did not decrease immune activation but had a detrimental effect on CD4 cell count and increased HIV viral replication in patients with chronic HIV infection who were not receiving antiretroviral therapy. Alternative interventions are needed to reduce immune activation and disease progression in early HIV infection.”

(JAMA. 2012;308[4]:353-361.


Liver Disease Stage Associated With Risk of Liver-Related Complications and Death Among Persons Infected With HIV and Hepatitis C


Berkeley N. Limketkai, M.D., of the Johns Hopkins University School of Medicine, Baltimore, and colleagues conducted a study to determine the rates of end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), or death (all-cause and liver-related mortality) among human immunodeficiency virus/hepatitis C virus coinfected adults.

“Hepatitis C virus (HCV) coinfection occurs frequently in persons infected with the human immunodeficiency virus (HIV) because of shared routes of acquisition,” according to background information in the article. “Human immunodeficiency virus accelerates hepatitis C virus disease progression; however, the effect of liver disease stage and antiviral therapy on the risk of clinical outcomes is incompletely understood.”

The study included 638 coinfected adults (80 percent black, 66 percent men) receiving care at the Johns Hopkins HIV clinic and receiving a liver biopsy and who were prospectively monitored for clinical events between July 1993 and August 2011 (median [midpoint] follow-up, 6 years). Histological specimens were analyzed for hepatic fibrosis stage.

The researchers found that patients experienced a graded increased risk in incidence of clinical outcomes based on baseline hepatic fibrosis stage. “Importantly, we found that HIV treatment with antiretroviral therapy, higher CD4 cell count, and effective HCV treatment were associated with significantly lower risk of clinical outcomes including those related to liver disease in some cases. As such, our findings have potential implications with respect to liver disease staging and initiation of antiviral therapy for coinfected persons.”

(JAMA. 2012;308[4]:370-378.


Patients With HIV Appear More Likely To Have Increased Inflammation of Arterial Walls, Which Increases Risk For Cardiovascular Disease


Sharath Subramanian, M.D., of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues examined whether arterial wall inflammation is increased in patients with HIV compared with patients not infected with HIV with similar cardiac risk factors.

“Coronary artery disease (CAD) is significantly increased in patients infected with human immunodeficiency virus (HIV), but the specific mechanisms remain unknown,” according to background information in the article.

The study, which included 81 participants, was conducted from November 2009 through July 2011. Twenty-seven participants with HIV without known cardiac disease underwent a cardiac imaging test (18fluorine-2-deoxy-D-glucose positron emission tomography [18F-FDG-PET]) for assessment of arterial wall inflammation and coronary computed tomography scanning for coronary artery calcium. The HIV group was compared with 2 separate non-HIV control groups. One control group (n=27) was matched to the HIV group for age, sex, and Framingham risk score (FRS; a measure of cardiovascular risk) and had no known atherosclerotic disease (non-HIV FRS-matched controls). The second control group (n=27) was matched on sex and selected based on the presence of known atherosclerotic disease (non-HIV atherosclerotic controls).

The researchers found that HIV infection was associated with a high degree of inflammation within the arterial wall, even in patients with low FRS and well-controlled viremia. “These findings advance our understanding of the unique pathophysiology and predilection to early increased CVD among patients infected with HIV …” the authors write. “These data have clinical relevance and suggest that patients with HIV with chronic infection have significant vascular inflammation, and thus added CVD risk, beyond that estimated by traditional risk factors. This information should now be considered in determining optimal monitoring and CVD prevention strategies for this group.”

(JAMA. 2012;308[4]:379-386.


Proportion of Patients Receiving Antiretroviral Therapy With Sustained Viral Suppression Increases Over Past Decade


Baligh R. Yehia, M.D., M.S.H.P., M.P.P., of the University of Pennsylvania Perelman School of Medicine, Philadelphia, and colleagues conducted a study to examine the change in and determinants of sustained viral suppression over time in HIV-infected adults receiving antiretroviral therapy (ART).

As reported in a Research Letter, the study included HIV-infected adults who initiated care at 12 high-volume HIV clinics that are part of the HIV Research Network (HIVRN). Clinics are located in the Northeastern (n = 6), Midwestern (n = l), Southern (n = 2), and Western (n = 3) sections of the United States. Patients were offered enrollment in the HIVRN. A total of 32,483 patients received care at the 12 clinics between 2001 and 2010.

The researchers found that the percentage of patients receiving ART with sustained viral suppression increased from 45 percent in 2001 to 72 percent in 2010. “Sustained viral suppression was lower for blacks and injection drug users during all 10 years. Older individuals and those with private insurance were more likely to have sustained viral suppression compared with younger patients and those with Medicaid, Medicare, or who were uninsured.”

The authors write that new drugs and combination fixed-dose tablets have enhanced the efficacy, safety, and tolerability of regimens. “Better access to care and adherence to treatment may also have contributed to improved virologic suppression.”

(JAMA. 2012;308[4]:339-342.





HIV/AIDS in 1990 and 2012 - From San Francisco to Washington, D.C.


Robert Steinbrook, M.D., of the Yale School of Medicine, New Haven, Conn., examines the changes in treatments and policies for HIV/AIDS that have occurred since the last time the International AIDS Conference was held in the U.S., in 1990, to this month’s conference in Washington, D.C.

Dr. Steinbrook discusses the successes and disappointments over this time period, including the advent of highly active antiretroviral therapy, and the absence of an AIDS vaccine.

(JAMA. 2012;308[4]:345-346.

The Future of HIV Prevention in the United States


Jonathan Mermin, M.D., M.P.H., and Kevin A. Fenton, M.D., Ph.D., of the Centers for Disease Control and Prevention, Atlanta, write that in the last 15 years, there’s been a 60 percent increase of the number of people in the U.S. living with HIV, to 1.1 million people. “The increasing number of people who can potentially transmit HIV makes prevention more difficult.”

In this Viewpoint, the authors discuss challenges and strategies of HIV prevention efforts in the U.S. “The United States has an opportunity to shift from supporting hundreds of different HIV prevention approaches to objectively assessing current HIV strategies, focusing on more cost-effective activities, and conducting research that will establish the groundwork for the future. This shift should help improve the effectiveness of HIV prevention efforts, reduce HIV incidence, and ultimately increase the possibility of achieving an AIDS-free America.”

(JAMA. 2012;308[4]:347-348.


Aging and HIV-Related Cognitive Loss


Farrah J. Mateen, M.D., of Johns Hopkins University, Baltimore, and Edward J. Mills, Ph.D., of the University of Ottawa, Ontario, Canada, write that cognitive disorders related to HIV remain an important burden of disease and disability worldwide, and that conservative estimates from better resourced countries suggest that the number of individuals of all ages living with HIV-related cognitive disorders will increase 5- to 10- fold by 2030.

The authors add that complicating HIV-related neurocognitive disorders is older age, which is the major risk factor for multiple forms of cognitive decline. They discuss strategies needed to address the issues related to aging and HIV-related cognitive decline. “An improved understanding of cognitive function in individuals with HIV infection would promote a better understanding of the epidemic of cognitive decline and provide an opportunity for scientific and community discussion on interventions that can be offered in a culturally relevant manner.”

(JAMA. 2012;308[4]:349-350