News Tips From XVI International Conference on AIDS

STUDY SHOWS ISONIAZID PLUS ANTIRETROVIRAL THERAPY BEST PREVENTS TB IN PEOPLE WITH HIV(Scheduled for presentation at 12:30 p.m. EDT, Monday, Aug. 14; poster presentation #MOPE395, Poster Exhibition Area, Level 800, South Building of Metro Toronto Convention Center.)

A study by Johns Hopkins and Brazilian scientists shows that pairing a common tuberculosis drug, isoniazid, with highly active antiretroviral therapy (HAART) is more effective than either therapy on its own at preventing full-blown TB disease in people with HIV.

TB disease remains the leading cause of death worldwide among those with HIV and AIDS and is epidemic in developing countries with the highest HIV-infection rates.

A team of Johns Hopkins and Brazilian researchers reviewed the medical records of 11,036 HIV-positive men and women in Rio de Janeiro, Brazil, one of 22 countries most affected by TB, and found that among those treated with both drugs, the risk of developing TB disease was reduced by 67 percent. Isoniazid on its own reduced the frequency of disease from the highly contagious tubercle bacillus by 32 percent. Scientists have known for years that HAART on its own reduced the risk of TB, by 51 percent in this survey, but they did not know until now the drugs' combined effects.

In the Johns Hopkins survey, sicker patients -- those with immune cell CD4 counts of less than 350 per cubic milliliter of blood -- were found to benefit more, with a 66 percent reduced risk of TB, compared to those with higher CD4 counts, whose risk went down by 56 percent.

Jonathan Golub, Ph.D., an assistant professor of infectious diseases at The Johns Hopkins University School of Medicine, says the results offer the first evidence that combination antiretroviral therapy with isoniazid could confer the best chance of preventing TB disease in people co-infected with HIV and TB. Study senior author Richard Chaisson, M.D., a professor of infectious diseases at Johns Hopkins and founding director of its Center for Tuberculosis Research, notes that while isoniazid treatment is recommended by the World Health Organization to prevent TB in HIV patients, most physicians fail to prescribe the drug, which costs less than $1 for a full course of therapy.

The study team will continue to monitor how well the drugs, both in combination and alone, help reduce the number of new cases of TB disease within the HIV-infected population of Rio de Janeiro. Their research is part of three ongoing studies by the Consortium to Respond Effectively to the AIDS/TB Epidemic, known as CREATE, that is led by Chaisson at Johns Hopkins and funded by the Bill and Melinda Gates Foundation. The goal of researchers in CREATE is to develop novel strategies to detect and treat latent TB infection and active TB disease in patients also infected with HIV. Worldwide, each year, more than 9 million new cases of TB are diagnosed, and more than 2 million people die from the disease, caused by Mycobacterium tuberculosis.

Tuberculosis (TB) incidence by HAART and isoniazid prophylactic therapy (IPT) in HIV-infected patients in Rio de Janeiro, Brazil. Jonathan Golub, V. Saraceni, S. Cavalcante, A. Pacheco, I. Moulton, B. King, R. Moore, Richard Chaisson, and B. Durovni

LESS-EXPENSIVE TESTS TO DETECT PERSISTANT HIV INFECTION AREN'T UP TO THE JOB, SCIENTISTS SAY (Scheduled for presentation at 12:30 p.m. EDT, Monday, Aug. 14; poster presentation #MOPE0124, Poster Exhibition Area, Level 800, South Building of Metro Toronto Convention Center.)

At a time when millions of people in rural Africa are gaining access to much-needed antiretroviral therapies to fight HIV, researchers from Johns Hopkins and elsewhere will present results showing that relatively inexpensive methods more widely recommended to monitor disease progression fall short of expectations after treatment starts.

Johns Hopkins researchers evaluated the sensitivity of two popular, relatively inexpensive tests, Dynabeads and Cytospheres. The tests count blood levels of key immune system cells, CD4 T-cells, which fight HIV. Combinations of antiretroviral therapy raise the number of CD4 T-cells while simultaneously lowering the level of viral activity in the blood, or so-called viral load.

Using blood samples from more than 497 HIV-positive men and women being treated with highly active antiretroviral therapy (HAART) at the Infectious Diseases Institute in Kampala, Uganda, the Johns Hopkins team used low-cost tests to measure CD4 T-cells at the start of therapy and at three-month intervals for up to a year and half. The patients also had benefit of the so-called gold-standard test, a more expensive procedure using flow cytometry.

On average, researchers say, single tests using Dynabeads cost $6, and for Cytospheres, $10. The relatively affordable tests can be read in an outpatient setting with the aid of a low-tech, light microscope that costs on average $750. By contrast, a FACSCount flow cytometry machine can cost over $35,000, and the average test price is $25.

Results showed that although Dynabeads and Cytospheres were highly accurate at the onset of therapy (98 percent and 93 percent, respectively) in counting CD4 T-cells after three months of HAART, when CD4 T-cell counts rose above 200 per cubic milliliter of blood, test sensitivity dropped to 31 percent and 55 percent.

Such decreased sensitivity, researchers say, means the tests could underestimate levels of immune cells, making it only possible to detect when the immune system is on the upswing and not when it is faltering.

On further analysis, the scientists found that the cheaper tests underestimated the actual number of failures by 5 percent and 27 percent, respectively. Even flow cytometry was not that effective at correctly monitoring failures, at 17 percent. Catching these cases is important in HAART because the infected person must be quickly switched to a different drug combination before viral resistance builds up.

Infectious disease specialist Lisa Spacek, M.D., Ph.D., who led the study by researchers in the United States, Canada and Uganda, says physicians in Africa need to know the limitations of the cheaper tests as they treat more people with HAART. Current World Health Organization guidelines recommend monitoring of CD4 T-cell counts as a means of tracking patients' response to HAART. But Spacek cautions that more expensive testing for viral load is the only validated option left for accurately tracking treatment failures.

Comparison of two manual-based bead assays, Dynabeads and Cytospheres, to FACScount at a public, urban clinic in Kampala, Uganda. F. Lutwama, Hasan Shihab, David Serwadda, M. Kamya, H. Mayanja, Thomas Quinn, A. Ronald, and Lisa Spacek

THREE-IN-ONE COMBINATION THERAPY CONTINUES TO SET NEW GOLD STANDARD IN ANTIRETROVIRAL THERAPY, LATEST DATA SHOW (Scheduled for presentation at 12:30 p.m. EDT, Tuesday, Aug. 15; poster presentation #TUPE0064, Poster Exhibition Area, Level 800, South Building of Metro Toronto Convention Center.)

A once-daily dose of three antiretroviral drugs works better as an initial treatment for HIV infection than another three-drug combination long considered to be the gold standard, according to the latest, year-two results from an international study being led by researchers at Johns Hopkins and elsewhere.

About 40,000 Americans each year are infected with HIV, the virus that causes AIDS.

Results showed that a daily regimen of a so-called triple cocktail, consisting of tenofovir DF (Viread) and emtricitabine (Emtriva), and efavirenz (Sustiva), suppressed the virus to undetectable levels in 75 percent of patients, compared to 62 percent of those who took another widely used combination of antiretrovirals, zidovudine and lamivudine (AZT and 3TC, or Combivir), plus efavirenz.

The U.S. Food and Drug Administration approved on July 12 the combination of tenofovir, emtricitabine and efavirenz as a once-a-day, single-pill HIV therapy, called Atripla.

Results from Study 934, which is expected to continue for another year, come after 96 weeks of therapy (two years in clinical terms) and involved 517 patients in the United States, France, Germany, Italy, Spain and the United Kingdom. The latest results support the initial, 48-week findings that were published in The New England Journal of Medicine on Jan. 19, 2006. Participants included both men and women, with an average age of 36, none of whom had been previously treated for their HIV infection. Each was randomly assigned to start treatment with either the tenofovir-emtricitabine or zidovudine-lamivudine regimen, each in combination with efavirenz. Their progress was monitored through blood tests, pill counts and regular check-ups at their medical clinic.

While both regimens were generally well tolerated, more patients in the zidovudine-lamivudine group dropped out of the study due to side effects, especially anemia. Some evidence of progressive lipoatrophy, a loss of fat in the limbs and face, which is not being seen in the tenofovir-emtricitabine group, was also observed in this group.

According to the lead study author, Joel Gallant, M.D., M.P.H., professor and associate director of the AIDS Service at The Johns Hopkins University School of Medicine, the tenofovir-emtricitabine combination shows superior activity due to better tolerability. Gallant says the body-fat results after two year suggest that even patients doing well on the zidovudine-lamivudine combination may benefit from switching to the newer combination.

Efficacy and safety of tenofovir DF (TDF), emtricitabine (FTC), and efavirenz (EFV) compared to fixed dose zidovudine/lamivudine (CBV) and EFV through 96 weeks in antiretroviral treatment-naïve patients. Joel Gallant, Anton Pozniak, Edwin DeJesus, José Arribas, Raphael Campo, S.S. Chen, Damian McColl, Jeffrey Enejosa, and Andrew Cheng.

EMERGENCY ANTI-HIV DRUG PLAN "AMAZING SUCCESS" IN UGANDA (Scheduled for presentation at 12:30 p.m. EDT, Thursday, Aug. 17; poster presentation #THPE0181, Poster Exhibition Area, Level 800, South Building of Metro Toronto Convention Center.)

Early results from a large study of HIV-infected people in rural Uganda show that seven out of 10 who got free, emergency access to antiretroviral drugs successfully suppressed the AIDS virus in their blood to nearly undetectable levels. The findings are being presented by researchers at Johns Hopkins and the Rakai Health Sciences Program who are leading the study.

Access to the drugs, provided at a reduced cost of less than $400 per year to Ugandan aid organizations, comes from the President's Emergency Plan for AIDS Relief (PEPFAR), inaugurated in January 2003. PEPFAR currently provides free access to drug therapy for approximately 400,000 people in sub-Saharan Africa infected with HIV, treatments that can cost upwards of $12,000 per year in the United States.

The two-year study of the free-access program involved 510 newly diagnosed men and women, average age 36, in the largely rural Rakai District of Uganda. All were in the advanced stages of AIDS and most in need of therapy. Study participants came from the Rakai cohort, a population of 12,000 people in Uganda who are being monitored to determine how HIV spreads in the country.

Subjects received standard triple-drug combination therapy and were monitored through semiannual check-ups and blood tests. Drug combinations used included treatment with either stavudine (d4T) or zidovudine (AZT) plus lamivudine (3TC), plus nevirapine (Viramune) or efavirenz (Sustiva). Treatment was provided in mobile clinics, such as medical officers on motorcycles riding from town to town.

Some 264 completed therapy as prescribed for a six-month period between check-ups. By January 2006, 216 (81 percent) had satisfactory increases in the number of key CD4 immune cells needed to fight infection, above 50 cells per cubic milliliter of blood. Some 166 (63 percent) had fully suppressed levels of the virus in their blood, at less than 400 viral copies per cubic milliliter of blood.

Steven J. Reynolds, M.D., M.P.H., lead researcher, says the results "are an amazing success story and demonstrate how a global relief program can dramatically suppress the virus, even among the rural, hard-to-reach populations in Africa." Reynolds adds that having two-thirds of an infected population with undetectable viral loads is a treatment-progress story from Africa comparable to any program in North America or Europe.

Early immunologic and virologic responses to ART in rural Rakai, Uganda. Steven J. Reynolds, J. Kagaayi, Godfrey Nakigozi, F. Makumbi, P. Opendi, P. Nakamya, Ronald Gray, Thomas C. Quinn, Maria Wawer, T. Lutalo, and David Serwadda