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Making It Harder For HIV To Hide From Drugs

April 21, 2011

The virus that causes AIDS is chameleon-like in its replication. As HIV copies itself in humans, it constantly mutates into forms that can evade even the best cocktail of current therapies. Understanding exactly how HIV cells change as they reproduce is key to developing better tests and treatments for patients.

In the Journal of Biological Chemistry and Nature Structural & Molecular Biology, MU microbiologist and biochemist Stefan Sarafianos, PhD, reveals new findings that shed light on how HIV eludes treatment by mutating. His discoveries provide clues into HIV's mechanisms for resisting two main families of drugs.

"These findings are important because identifying a new mutation that affects HIV drug resistance allows physicians to make better decisions and prescribe the proper drugs," Sarafianos said. "Without that knowledge, therapy can be suboptimal and lead to early failure."

Patients with HIV are routinely tested to track the levels of the virus and immune cells in their body. Results of the tests help physicians gauge the health of their patients and prescribe the right mix of antiviral drugs. The drugs help prevent the spread of HIV in patients by inhibiting the virus' ability to replicate.

Sarafianos' lab determined the biochemical properties that allow strains of HIV with a specific mutation - the N348I mutation - to escape inhibition despite treatment with Nevirapine. The drug is commonly used in combination with other antiviral medications to decrease the amount of HIV in the blood. As a result of Sarafianos' discovery, at least one major company that manufactures HIV mutation-testing kits has modified its test to detect the N348I mutation.

Sarafianos' recent findings resulted from research supported by five National Institutes of Health grants. He recently received another $417,000 award from the NIH to assist him in developing modified antibodies for HIV therapy.

"Our latest efforts to design broadly neutralizing antibodies against HIV will hopefully expand our toolbox against the virus, which remains a constantly moving target," Sarafianos said.

Natalie Fieleke
University of Missouri School of Medicine

Tags: HIV, Drugs

Ten Million Deaths And 1 Million New HIV Infections Could Be Averted If Countries Meet HIV Treatment Targets

April 03, 2011

The new UNAIDS Outlook report outlines a radically simplified HIV treatment platform called Treatment 2.0 that could decrease the number of AIDS-related deaths drastically and could also greatly reduce the number of new HIV infections. Evidence shows that new HIV infections among young people, in the 15 countries most affected by HIV, are dropping significantly as young people embrace safer sexual behaviours.

Also in the report, a sweeping new UNAIDS and Zogby International public opinion poll shows that nearly 30 years into the AIDS epidemic, region by region, countries continue to rank AIDS high on the list of the most important issues facing the world.

And an economic analysis makes the case for making health a necessity, not a luxury, outlining the critical need for donor countries to sustain AIDS investments and calling on richer developing countries to invest more in HIV and health.

The report was launched in Geneva ahead of the XVIII International AIDS Conference in Vienna. The UNAIDS Executive Director, Mr Michel Sidibé, stressed that innovation in the AIDS response can save more lives. "For countries to reach their universal access targets and commitments, we must reshape the AIDS response. Through innovation we can bring down costs so investments can reach more people."

According to UNAIDS' estimates there were 33.4 million people living with HIV worldwide at the end of 2008. In the same year there were nearly 2.7 million new HIV infections and 2 million AIDS-related deaths.

Treatment 2.0 saves lives

Treatment 2.0 is a new approach to simplify the way HIV treatment is currently provided and to scale up access to life saving medicines. Using a combination of efforts it could bring down treatment costs, make treatment regimens simpler and smarter, reduce the burden on health systems and improve the quality of life for people living with HIV and their families. Modelling suggests that compared with current treatment approaches, Treatment 2.0 could avert an additional 10 million deaths by 2025.

In addition, the new approach could also reduce new HIV infections by up to 1 million annually if countries provide antiretroviral therapy to all people in need, following revised WHO treatment guidelines. Today, 5 million of the 15 million people in need are accessing these life-saving medicines.

To achieve the full benefits of Treatment 2.0 progress has to be made across five areas:

1. Create a better pill and diagnostics: UNAIDS calls for the innovation of a smarter, better pill that is less toxic and for diagnostics that are easier to use. Monitoring treatment requires complex equipment and specialized laboratory technicians. A simple diagnostic tool could help to reduce the burden on health systems. Such a simplified treatment platform could defray costs and increase people's access to treatment.

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2. Treatment as prevention: antiretroviral therapy reduces the level of the virus in the body. Evidence shows that when people living with HIV have lowered their viral load they are less likely to transmit HIV. It is estimated that ensuring everyone in need has access to treatment, according to the current treatment guidelines, could result in up to a one third reduction in new HIV infections annually. Optimizing HIV treatment coverage will also result in other health prevention benefits, including much lower rates of tuberculosis and malaria among people living with HIV.

3. Stop cost being an obstacle: despite drastic reductions in drug pricing over the past ten years, the costs of antiretroviral therapy programmes continue to rise. Drugs can be even more affordable-however, potential gains are highest in the area of reducing the non-drug-related costs of providing treatment, such as hospitalization, monitoring treatment, and out-of-pocket expenses. Currently these costs are twice the cost of the drugs themselves. Treatment 2.0 is expected to reduce the cost per AIDS-related death averted by half.

4. Improve uptake of voluntary HIV testing and counselling and linkages to care: when people know their HIV status they can start treatment when their CD4 count is around 350, rather than waiting until they are feeling sick. Starting treatment at the right time increases the efficacy of current treatment regimens and increases life expectancy.

5. Strengthen community mobilization: by involving the community in managing treatment programmes, treatment access and adherence can be improved. Demand creation will also help bring down costs for extensive outreach and help reduce the burden on health care systems.

"Not only could Treatment 2.0 save lives, it has the potential to give us a significant prevention dividend," said Mr Sidibé, speaking at the launch of the report.

Young people leading the prevention revolution

A new UNAIDS study shows that young people are leading the HIV prevention revolution. HIV prevalence among young people has declined by more than 25% in 15 of the 25 countries most affected by AIDS. These declines are largely due to falling new HIV infections among young people.

In eight countries-Côte d'Ivoire, Ethiopia, Kenya, Malawi, Namibia, the United Republic of Tanzania, Zambia and Zimbabwe-significant HIV prevalence declines have been accompanied by positive changes in sexual behaviour among young people.

For example, in Kenya there was a 60% decline in HIV prevalence between 2000 and 2005. HIV prevalence dropped from 14.2% to 5.4% in urban areas and from 9.2% to 3.6% in rural areas in the same period. Similarly in Ethiopia there was a 47% reduction in HIV prevalence among pregnant young women in urban areas and a 29% change in rural areas.

Young people in 13 countries, including Cameroon, Ethiopia, and Malawi, are waiting longer before they become sexually active. Young people were also having fewer multiple partners in 13 countries. And condom use by young people during last sex act increased in 13 countries.

There are 5 million young people living with HIV worldwide, making up about 40% of new infections.

The Benchmark survey

An international public poll on HIV commissioned for the first time by UNAIDS shows that nearly 30 years into the AIDS epidemic, region by region, countries continue to rank AIDS high on the list of the most important issues facing world. For example, in India about two thirds report that the AIDS epidemic is more important than other issues the world is currently facing.

Overall, respondents put AIDS as the top health-care issue in the world. Furthermore, about half of the respondents are optimistic that the spread of HIV can be stopped by 2015.

There is recognition of efforts to raise public awareness about HIV over the course of the AIDS response, with one in three respondents considering it the greatest achievement of the response so far. This was followed by implementation of HIV prevention programmes and the development of new antiretroviral drugs.

When asked about how their country was doing against the epidemic, about 41% of respondents said that their country was dealing effectively with the problem. Only one in three people believe the world is responding effectively to AIDS.

For 62% of people surveyed in Sweden, the availability of funding/resources or the availability of affordable health care is keeping the world from effectively responding to HIV. Some 60% of people in the United Kingdom also felt that the lack of funding was the main obstacle. Other challenges cited by the people surveyed mirror on the ground experience, with more than half of respondents saying the availability of prevention services was the most important obstacle-stigma and discrimination were cited as another barrier.

When it came to HIV treatment, nearly six in ten believe it is the duty of the state to provide for free or subsidized treatment for people living with HIV.

The poll surveyed adults in 25 countries representing all regions with nearly 12,000 respondents.

Investments in HIV must be sustained, efficient and predictable

Investment in HIV is smart and proven. At this turning point, flat-lining or reductions in investments will hurt the AIDS response. In 2010 an estimated US$ 26.8 billion is required to meet country-set targets for universal access to HIV prevention, treatment, care and support.

"The AIDS response needs a stimulus package now. Donors must not turn back on investments at a time when the AIDS response is showing results," said Mr Sidibé. "The 0.7% target on international aid and the Abuja target of 15% for health cannot be buried."

UNAIDS recommends that national HIV programmes invest between 0.5% and 3% of government revenue in the AIDS response. In recent years many countries have increased their domestic investments in the AIDS response. For example, the South African Government increased its budget for AIDS by 30% to US$ 1 billion in 2010. However, for the majority of the countries severely affected by AIDS, domestic investments alone, even when raised to optimal levels, will not suffice to meet all their resource needs.

UNAIDS calls on richer developing countries to meet a substantial proportion of their resource needs from domestic sources. Currently, 50% of the global resources requirement for low- and middle-income countries is in 68 countries where the national need is less than 0.5% of their gross national income. These countries have 26% of the people living with HIV and receive 17% of international assistance for AIDS.

According to the report, current investments in HIV can become more efficient, effective and predictable. "We can bring down costs so investments can reach more people," said Mr Sidibé. "This means doing things better-knowing what to do, channelling resources in the right direction and not wasting them, bringing down prices and containing costs. We must do more with less."


Tags: HIV, Drugs


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