Preventive Antibiotics for Tuberculosis Reduce Deaths Among People With HIV Disease

The research team's findings, stem from what is believed to be the largest expansion of a clinic-based, community health program designed to curb the spread of TB, and the first evidence that such a community-wide effort can be highly effective at preventing people who are co-infected from developing active TB disease.

According to senior study investigator and Johns Hopkins infectious disease specialists Richard Chaisson, M.D., his team's latest study results firmly support broad use of preventive isoniazid therapy for millions of people infected with HIV in Latin American, Asian, and Eastern European countries heavily burdened by TB.

Chaisson says TB disease remains the leading cause of death worldwide among those with HIV/AIDS and is epidemic in developing countries with the highest HIV-infection rates. Isoniazid treatment, which costs less than $1 for a full course of therapy, is already recommended by the World Health Organization to prevent TB in people with HIV disease. The policy, however, has not been widely adopted and its broad impact on the HIV-infected community never shown until the Johns Hopkins and Brazilian team's latest study.
All of the 12,816 study participants were eligible for screening for TB infection or active TB disease. Some 1,186 tested positive for TB infection, but did not have symptoms of TB sickness and could start taking 300 milligrams of isoniazid daily for six months. All received routine follow-up care for as little as a few weeks to as long as four years after initially seeking treatment at any of 29 HIV clinics across Brazil, a country hit hard by both infectious diseases. Some 838 deaths occurred during the study, which took four years to complete, and 475 developed TB. Symptoms of active TB disease, indicating the disease has progressed from latent infection, include persistent cough, chest pain, chills, fever, muscle weakness and fatigue.
"Our study results show that routine testing for TB and preventive isoniazid therapy works well at the community level in people with HIV disease in curbing the spread of TB and lowering the number who die," says Chaisson, a professor at the Johns Hopkins University School of Medicine and founding director of its Center for Tuberculosis Research.

"People with HIV disease living in all countries with rampant TB should be asking their physicians if they are good candidates for preventive isoniazid therapy," says Chaisson, who leads the overall global research effort, in support of this study and others, called the Consortium to Respond Effectively to the AIDS/TB Epidemic. CREATE, as it is known, is funded by the Bill and Melinda Gates Foundation.
When researchers restricted their analysis to 12,196 study participants who kept at least one annual check-up appointment, the overall death rate and number of new TB cases was even lower, at 55 percent. The number of active TB cases decreased by 58 percent. Among study participants who received isoniazid, commonly marketed under the brand names Niazid, Laniazid and Nydrazid, 85 percent took a full course of drugs for six months, as prescribed.

Another important finding, researchers say, was that initial TB screening of those seeking HIV care led to diagnosis of over a third (34 percent, or 250) of the total 725 new clinic patients found to have active TB. All were offered treatment for their disease but were excluded from the study analysis.

Lead study investigator and Johns Hopkins epidemiologist Jonathan Golub, Ph.D., M.P.H., says the study was, on its own, an effective screening tool, and affirms how unknown TB cases can be found when public health officials focus on community health programs in local clinics that service people more likely to become infected. In Brazil, an estimated 10 percent of people diagnosed with TB sickness are co-infected with HIV.
Golub says further research is needed to determine how long lasting are isoniazid's protective effects are and whether the single course of treatment used in the latest study is sufficient, or if repeat or lifelong antibiotic therapy is needed to suppress TB.

"Our efforts highlight the importance of continuous training in diagnosing TB, and our immediate priority is to train community doctors and nurses in HIV clinics to make TB testing part of routine HIV care," says Golub, an associate professor at Johns Hopkins. Golub points out that in Brazil, TB screening policies have been in place since 1995, but simply not followed. Golub says that once clinics involved in the study began more rigorous screening, the number of initial TB skin tests performed jumped threefold, and the number of patients taking isoniazid went up fourfold.

For the study, clinic staff were rigorously trained in correct procedures for screening all patients with HIV for possible TB infection and signs of active TB disease. Patients who tested positive for active TB disease were offered treatment, but were not included in study monitoring. Those who met study criteria were offered preventive isoniazid therapy. To detect TB, a simple skin test is initially performed, which if positive for signs of an immune response, can lead to further, confirmatory lab and X-ray testing.

Intensive training at all 29 clinics was randomly staggered every two months, allowing staff at all clinics to eventually benefit from the enhanced study effort. The staggered timeline also gave researchers a long period to assess isoniazid's effects pre- and post-training. Study participants were 61 percent male, and on average 37 years old. Sixty percent were receiving antiretroviral therapy for HIV.

Chaisson says the team next plans to evaluate faster diagnostic tests for TB, other than the initial skin test, which takes only minutes to administer, but requires a 48-hour waiting period to show any reaction. He says the ideal test would be a blood test that could be performed at the same time as routine anti-HIV tests for blood levels of CD4 immune cells.

Brain functioning in HIV-infected adults improved by Exercise

Regular exercise is not only good for health, but can give people living with HIV a significant mental boost. This is according to a study by Dr. David J. Moore and colleagues at the University of California, San Diego (UCSD)

The study found that HIV-infected adults who exercise suffered significantly less neurocognitive impairment compared to patients who do not exercise.

Moore and his team, including UCSD medical student Catherine Dufour, found that HIV-infected adults who exercise were approximately half as likely to show signs of neurocognitive impairment as compared to those who do not. They also had better working memory and could process information faster than patients who follow a sedentary lifestyle.

Despite recent advances in antiretroviral treatment, impaired brain functioning is a reality faced by nearly half of all people living with HIV. This ranges from asymptomatic neurocognitive impairment, to more pronounced deficits that interfere with daily functioning, such as problems with financial management, driving and taking medication regularly.

The major benefit of exercise to the brain seems to be the reduction of neurocognitive risk factors, such as high blood pressure and abnormally high levels of lipids in the blood. Metabolic syndrome associated with the use of antiretroviral treatment is also linked to an increase in cerebrovascular risk factors, such as diabetes, hypertension and obesity.

In the study, 335 community-dwelling HIV-infected people were asked how much exercise they undertook during the previous 72 hours, and persons were classified into those who engaged in significant exercise (e.g., activities that make the heart beat rapidly) and those who did not. Seven cognitive areas commonly affected by HIV were tested, including verbal fluency, working memory, speed of information processing, learning, recall, executive function and motor function.

The study extends prior findings about the link between exercise and cognition among HIV-infected people by showing that this association is also true in a diverse and large group of people living with the disease. Compounding factors were taken into account, such as demographics, HIV disease characteristics, substance use, past and current depression, mental health status and physical functioning.

"Exercise as a modifiable lifestyle behavior may reduce or potentially prevent neurocognitive impairment in HIV-infected persons," says Moore. "Physical exercise, together with other modifiable lifestyle factors such as education, social engagement, cognitive stimulation and diet could be fruitful interventions to support people living with HIV."

HIV as You Get Older

Many people think of HIV as a young person's disease, but it's not. "By 2015, half of all people with HIV will be 50 or older," says Brad Hare, MD, director of the HIV/AIDS clinic at San Francisco General Hospital. This greying of the HIV population shows how well today’s HIV treatments can work.

HIV makes aging itself more complicated. But plenty of people have had HIV for years, even decades, and are doing well.  "These days, we fully expect that someone with HIV will live a long, healthy life," says Christine A. Wanke, MD, professor of medicine and director of the nutrition and infection unit at Tufts University School of Medicine. "But that means they have to plan ahead and adopt the healthy habits to stay that way, just like anyone without HIV."

HIV and Aging: 5 Common Challenges

As you get older with HIV, you may face issues including:

1. Other conditions. Just like anybody, getting older means you're more likely to have health problems, and HIV seems to bump up the risk even more. "HIV accelerates the aging process and magnifies its effects," says John G. Bartlett, MD, professor at the Johns Hopkins School of Medicine and director of its AIDS service. So HIV may make you more likely to get heart disease, diabetes, cancer, osteoporosis, kidney problems, and other conditions.

2. Drug interactions. Since you’re already taking medicines for HIV, additional drugs for other conditions can increase the chance of interactions.

3. Loss of support. Some people become more isolated as they age. That happens more often to people with HIV, who may also be dealing with embarrassment about the condition or strained family relationships. If you're alone and disconnected, you're more likely to get depressed.

4. Changing roles. Like many people without HIV, you may be caring for your aging parents. That can add emotional and financial pressures.

5. Difficulty adjusting. "I talk to people with HIV who say, 'I didn't expect to live to middle age,'" says Hare. "'But now I'm middle-aged and I'm probably going to live another 30 years.'" Many people who got HIV long ago didn't plan for a long life, and adjusting can be a challenge. For instance, you might not have saved for a longer life.

7 Steps to Take

1. See an HIV expert. The more your health is complicated by age and other conditions, the more crucial it is to have an expert overseeing your HIV care.

2. Get good routine medical care. Specialty HIV care is not enough. Because your risks of other medical problems are higher, keep on top of your general health, says Hare. Get your annual physicals, keep tabs on your blood pressure, cholesterol, and other tests your doctor recommends.

3. Avoid drug interactions. Make certain every doctor you see knows about every medication and supplement you take, including prescription drugs, over-the-counter products, vitamins, and natural products. Doctors may adjust your medicines, dosages, or schedules to prevent interactions.

4. Improve your lifestyle. To enjoy life as you age, stay fit. Exercise regularly, and if you smoke, stop.

5. Eat a healthy diet. Go for lots of fruits and vegetables, lean proteins, whole grains, and healthy fats. "Eating a heart-healthy diet makes sense for everyone," says Bartlett. "But because people with HIV have higher risks of heart disease, it makes even more sense for them."

6. Seek support. Having a support system of family and friends is key. Make an effort to stay connected. If close friends or family have died or moved away, work on making new friends. You might also connect through a support group.

7. Get help. Call your local health department to learn about local resources for people with HIV, says Hare. Your local Council on Aging is a good place to start; it can point you toward programs and services that could help. A financial planner may also help you work on savings and expenses.

Plant-Based Compound May Inhibit HIV

A compound found in soybeans may become an effective HIV treatment without the drug resistance issues faced by current therapies

It's in the early stages, but genistein, derived from soybeans and other plants, shows promise in inhibiting the HIV infection, says Yuntao Wu, a professor with the George Mason-based National Center for Biodefense and Infectious Diseases and the Department of Molecular and Microbiology.

Still, that doesn't mean people should begin eating large amounts of soy products. "Although genistein is rich in several plants such as soybeans, it is still uncertain whether the amount of genistein we consume from eating soy is sufficient to inhibit HIV," Wu says.

Genistein is a "tyrosine kinase inhibitor" that works by blocking the communication from a cell's surface sensors to its interior. Found on a cell's surface, these sensors tell the cell about its environment and also communicate with other cells. HIV uses some of these surface sensors to trick the cell to send signals inside. These signals change cell structure so that the virus can get inside and spread infection.

But genistein blocks the signal and stops HIV from finding a way inside the cell. It takes a different approach than the standard antiretroviral drug used to inhibit HIV. "Instead of directly acting on the virus, genistein interferes with the cellular processes that are necessary for the virus to infect cells," Wu says. "Thus, it makes the virus more difficult to become resistant to the drug. Our study is currently it its early stage. If clinically proven effective, genistein may be used as a complement treatment for HIV infection."

Wu sees possibilities in this plant-based approach, which may address drug toxicity issues as well. Because genistein is plant-derived, it may be able to sidestep drug toxicity, a common byproduct of the daily and lifelong pharmaceutical regimen faced by patients with HIV to keep the disease at bay, Wu says. Typically, patients take a combination of multiple drugs to inhibit the virus. The frequency can lead to drug toxicity. Plus, HIV mutates and becomes drug-resistant.

Wu and his team are working at finding out how much genistein is needed to inhibit HIV. It's possible that plants may not have high enough levels, so drugs would need to be developed, Wu says.