All it takes is one

Kaiser Daily HIV/AIDS Report

Science & Medicine | Most HIV Cases Traced to Transmission of Single Virus, Study Finds

[May 22, 2008]

Most HIV cases can be traced to the transmission of a single virus, according to a study published online Monday in the Proceedings of the National Academies of Science, the Birmingham News reports. According to researcher George Shaw, a professor at the University of Alabama-Birmingham, the findings are surprising and could have an impact on HIV/AIDS vaccine development.

For the study, Shaw and colleagues analyzed blood samples from 102 people who had recently contracted HIV. The study was funded by NIH's National Institute of Allergy and Infectious Diseases and the Bill & Melinda Gates Foundation. The researchers genetically analyzed the samples and were able to count generations of HIV. They found that 76% of the cases could be traced back to a single virus. The remaining 24% could be traced to two to five viruses, according to Shaw. Shaw noted that in the "vast majority" of cases, a single virus has "gone across the sexual mucosa, and that virus has infected a cell." He added, "That cell then makes a lot of virus. Now you just have a firestorm of HIV replication in the next couple weeks. Very quickly the person is populated by millions of viruses." According to Shaw, the findings help explain why it usually takes several exposures for a person to contract HIV, why transmission of the virus is so inefficient and why condoms help prevent HIV transmission.

The findings are significant because they indicate that if researchers are "trying to develop a vaccine or microbicide or whatever to prevent [HIV] infection, the only thing it has to do is prevent the transmission of a single virus," Shaw said. He added, "That should be possible. All you have to do is provide some additional block to what already is an efficient process." The findings "provide light on what was previously a very cloudy area of HIV infection," Shaw said, adding, "It puts acute and early transmission of HIV-1 in very sharp focus."

Most other sexually transmitted infections -- such as gonorrhea and syphilis -- "invade the body en masse," according to the News. "They just all come across 10, 20, 100, 200 bacteria or spirochetes," Shaw said. Several research centers worldwide were involved in the project, including Duke University, the University of California-San Francisco, the University of Cape Town in South Africa, the University of Massachusetts-Amherst, the University of North Carolina-Chapel Hill, the University of Maryland, the University of Rochester, and the Los Alamos National Laboratory and the Santa Fe Institute in New Mexico (Parks, Birmingham News, 5/20).

The study is available online (.pdf).

Source: Kaiser Daily HIV/AIDS Report

The Quality Standards for Generic Drugs

Are Discount Drugs of Inferior Quality?

"Most people believe that if something costs more, it has to be better quality..."says Gary Buehler, Director of FDA's Office of Generic Drugs. "In the case of generics (discount drugs), this is not true. The standards for quality are the same for brand name and generic products." (1)

When a brand name product has a generic competitor, this simply means that the brand name product has been around long enough for its patent to expire, which then allows generics (copy discount drugs) to be made. Most often generics will be the discount drugs found in these markets, and almost always they will be less expensive prescription drugs when compared to their brand name counterparts.

Despite their lower price, manufacturers of generic prescription drugs are required to meet rigorous quality standards before they can sell their generic 'discount drugs'. Pharmacies who source high quality generic products only from pharmaceutical manufacturers that comply with these strict international regulatory standards are providing quality alternatives to the branded equivalent. The quality standards of the lower cost generic products available are as high as they are for the most expensive original brand name drugs .

While the active ingredients in generic prescription drugs are the same as the active ingredients in their brand name counterparts, there may be differences in their appearance. (For example, the shape or the colour of a tablet.)

Sometimes different non-active ingredients may used to produce the final product. (For example, the non-active base in creams or diluents in nasal sprays.) However, the active ingredients, which give a drug its intended effect, are the same in generic prescription drugs and their brand name counterparts. None of these differences should alter the clinical effect of any approved generic discount drug.

The Current Use of Generic Prescription Drugs

The U.S. drug regulatory authority, the FDA, has approved more than 7000 generic discount drugs for use in the U.S. The approval process that all of these generic prescriptions drugs have completed is extremely intensive and multi-faceted. It covers quality, performance and labelling. Also, while these generics will inevitably become the country's discount drugs, the manufacturing facilities where they are to be made, are required by the FDA to be as good as those used to manufacture brand name drugs. This standard applies no matter where in the world the manufacturing facility is located.

Almost half of the prescriptions filled in 2002 in the U.S. were for generic drugs (1), these being the discount drugs of the country. This strong and growing demand for generic prescription drugs is testimony to their widespread acceptance by the health authorities, health professionals, and patients.

Pharmacies source high quality generic products only from pharmaceutical manufacturers that comply with strict international manufacturing standards. This means that any generic product supplied to a customer has complied with robust internationally accepted quality standards.


Some of the generic products sourced from internationally approved pharmaceutical manufacturers from India. The key companies that supply Indian generic pharmaceuticals are:

• Dr Reddy's Laboratories Limited

• Cipla Limited

The links provided will take you to the respective company websites which have information to show that their manufacturing facilities have been inspected to meet the robust standards of the FDA as well as other internationally recognised regulatory authorities.

Some Technical Facts About The Generic Drug Approval Process

In the U.S and most developed countries generic drugs must show that they:

• Contain the same active ingredients as the brand name drug (inactive ingredients may vary)

• Are identical in strength, dosage, form, and route of administration

• Are used for the same condition(s)

• Are bio-equivalent (that is, they are available to the same extent in the body when taken or administered)

• Meet the same batch requirements for identity, strength, purity, and quality

• Are manufactured under the same strict standards of the FDA's good manufacturing practice as required for brand name products. (1)

Useful Links

To read more about the FDA standards for generic drugs click on the following links. http://www.fda.gov/opacom/factsheets/justthefacts/18generic.html
http://www.fda.gov/cder/about/whatwedo/testtube-17.pdf

FDA Approved AIDS Drugs

For those seeking treatment options, below is a listing of medications available in the USA. Please note that this list is not 100% complete, and does not include all possible available or recently approved medications. Also, it is possible to buy some of these medicines as generics and as such they would have different names.

• Agenerase (amprenavir) - Protease inhibitor.
• Aptivus® (tipranavir) - Protease inhibitor.
• Atripla; Three pills in one; combines the active ingredients of Sustiva (efavirenz), Emtriva (emtricitabine) and Viread (tenofovir disoproxil fumarate).
• Combivir -combination of Retrovir (300mg) and Epivir (150mg) - together in the same tablet for convenience.
• Crixivan (indinavir) - protease inhibitor.
• Emtriva [ emtricitabine (FTC).
• Epivir (3tc / lamivudine) - nucleoside analog reverse transcriptase inhibitor
• Epzicom ( a combination of 2 nucleoside reverse transcriptase inhibitors (NRTIs in the same pill; 600mg of Ziagen (abacavir) and 300mg of Epivir (3TC).
• Fortovase (saquinavir) - protease inhibitor.
• Fuzeon (enfuvirtide) - Fusion inhibitor.
• Isentress (raltegravir) Integrase Inhibitor.
• Invirase (saquinavir) - protease inhibitor.
• Kaletra (lopinavir) - protease inhibitor.
• Lexiva (Fosamprenavir) - Protease Inhibitor approved 10/20/03
  Formerly known as GW-433908 or VX-175
  Improved version of Agenerase ( amprenavir); supposed to be fewer pills per day and fewer GI Side effects.
• Norvir (ritonavir) - protease inhibitor.
• PREZISTA (darunavir) tablets. - protease inhibitor;
  used when other protease inhibitors don't work any more.
• Rescriptor (delavirdine) - non nucleoside analog reverse transcriptase inhibitor.
• Retrovir, AZT (zidovudine) - nucleoside analog reverse transcriptase inhibitor.
• Reyataz (atazanavir; BMS-232632) - protease inhibitor.
• Sustiva (efavirenz) - non nucleoside analog reverse transcriptase.
• Trizivir (3 non nucleosides in one tablet ; abacavir + zidovudine + lamivudine.
• Truvada (Emtricitabine + Tenofovir DF )
  Combination of 2 nucleoside reverse transcriptase inhibitor (NRTI's in one pill).
• Videx (ddl / didanosine) nucleoside analog reverse transcriptase inhibitor.
• Viracept (nelfinavir) - protease inhibitor.
• Viramune (nevirapine) - non nucleoside analog Reverse transcriptase inhibitor.
• Viread (tenofovir disoproxil fumarate) Nucleotide Reverse transcriptase inhibitor ( Adenosine Class).
• Zerit (d4t / stavudine) - nucleoside analog reverse transcriptase inhibitor.
• Ziagen (abacavir) - nucleoside analog reverse transcriptase inhibitor.

AIDS-Drugs-Online.com

New AIDS Drugs

According to Avert, an international AIDS charity, more than half a million people with AIDS have died in the United States. Since 1989, there have been at least 39,000 new AIDS diagnoses each year. Prevalence of the disease peaked in the United States in 1993, then showed a decline. The most dramatic drops in both cases and deaths began in 1996, with the widespread use of the combination antiretroviral therapy, or “drug cocktails.” While almost one million people have been diagnosed with AIDS, only an estimated 550,394 have died. The number of deaths among people with AIDS has remained stable since 1999. The drug cocktails have contributed significantly to this, but now, two new drug innovations could be the next big things in HIV and AIDS treatment. If they are as affective as researchers hope, those rates will not only remain stable -- they’ll go down.

NEW WEAPONS: The introduction of the drug cocktails made a major impact on the number of deaths from AIDS. Researchers hope two new classes of HIV and AIDS drugs could be the new "drug cocktails" of the 21st century. There are nearly 30 drugs in four different classes. The four existing classes of HIV and AIDS antiretroviral drugs each targeting the HIV virus in one of four different ways. With the introduction of two new drugs -- each representing a new class of HIV and AIDS drugs -- there will be a total of six different classes of drugs available. Doctors say the drugs should be used in combination with existing drugs to combat the disease in multiple ways.

ISENTRESS (raltegravir), manufactured by Merck, is the first medicine to be approved in the new integrase inhibitors class of antiretroviral drugs. ISENTRESS works by inhibiting the insertion of HIV DNA into human DNA by the integrase enzyme. Doing so limits the ability of the virus to replicate and infect new cells. There are drugs in use that inhibit two other enzymes critical to the HIV replication process, but ISENTRESS is the only drug that inhibits the integrase enzyme.

SELZENTRY (maraviroc), manufactured by Pfizer, is the first approved medicine in the CCR5 antagonists, which block the CCR5 co-receptor -- the virus' predominant entry route into T-cells. HIV enters cells in the blood by attaching itself to structures on the surface of the cell called receptors. SELZENTRY blocks a specific receptor called CCR5 that CCR5-tropic HIV-1 uses to enter T-cells in your blood.

Neither drug reduces the risk of transmitting HIV to others. HIV is spread through sexual contact, sharing needles or being exposed to an infected person's blood. Manufacturers caution the drugs will not cure HIV infection, but may slow the progression.

These medicines will likely be available first at AIDS-Drugs-Online.com

WHO Director-General Chan Calls on Member States To Make Antiretrovirals, Other Medications More Affordable

World Health Organization Director-General Margaret Chan on Monday at a meeting of WHO's Intergovernmental Working Group on public health in Geneva called on developed countries to make antiretroviral drugs and other medications more affordable for developing countries, the AP/Tacoma News Tribune reports. WHO's 193 member states by the end of the week hope to develop a strategy on drug development, patenting and pricing, according to the AP/News Tribune.

Chan at the meeting said she is aware that the "price of medicines and other products can be prohibitive, effectively blocking access to care," but she added that innovation is needed. "Resistance develops and drugs fail, creating an urgent need for second- and third-line medicines," Chan said, adding, "We have seen this problem most acutely with HIV/AIDS. We are seeing it again with the spread of extensively drug-resistant tuberculosis, which is far more costly and difficult to treat" (Klapper, AP/Tacoma News Tribune, 11/5).

Chan said, "The challenge is to work on multiple fronts: to meet the immediate need for equitable access to quality, affordable medicines, while also, at the same time, working to stimulate innovation." She added that the global health community "cannot allow the costs of health care to drive impoverished households even deeper into poverty."

Working Group
According to AFP/Yahoo! News, the working group was set up last year after a WHO-commissioned report called on pharmaceutical companies to reduce prices of drugs sold in developing countries. Some companies have said they already have reduced prices, and the International Federation of Pharmaceutical Manufacturers and Associations has said that drug price and patent issues fall under World Trade Organization jurisdiction and not WHO.

According to U.S. documents obtained by the lobby group Knowledge Ecology International, the U.S. urged countries attending the weeklong meeting to respect existing WTO commitments and not extend WHO's mandate. The U.S. "would like you to make sure you are aware of the potentially negative trade and intellectual property implications that could arise from this initiative" at WHO, the document said. James Love, director of KEI, said the U.S. and European Union are playing a "cynical game" in attempting to break the consensus toward making drugs more affordable (AFP/Yahoo! News, 11/5).

Related Opinion Pieces
Two newspapers on Tuesday published opinion pieces in response to the WHO meeting. Summaries appear below.

* Franklin Cudjoe, Wall Street Journal: Inadequate infrastructure, not price, is the "chief obstacle blocking access of high-quality medicine" in developing countries, Cudjoe, executive director of the Imani Center for Policy and Education, writes in a Journal opinion piece. "If the West is any guide, better health systems come with economic development and higher standards of living," both of which are "frequently stifled" in developing countries by "destructive policies and home-grown corruption," Cudjoe writes. "Let's hope the WHO won't succumb to the misconception that compulsory license can cure Africa's health problems," Cudjoe writes, concluding that "economic development remains the continent's best hope for eradicating the diseases of poverty" (Cudjoe, Wall Street Journal, 11/6).

* Jeremiah Norris, Taipei Times: WHO member states "need to knock this treaty on the head ... before the WHO does lasting damage to global public health," Norris, director of the Center for Science in Public Policy at the Hudson Institute, writes in a Times opinion piece. According to Norris, WHO "aims to weaken intellectual property further and to bring research and development under the control of governments and international bodies," adding that "past evidence shows that nationalizing any business stifles innovation and that it would hinder future efforts to create drugs" for developing countries (Norris, Taipei Times, 11/4).

Global Fund, Ryan White Program Would Receive Increases in Funding Under House-Passed FY 2008 Appropriations Bill

The House voted 269-142 to pass an appropriations bill that combines the fiscal year 2008 Labor-HHS-Education (HR 3043) and Military Construction-Veterans Affairs (HR 2642) appropriations bills, the AP/Arizona Daily Star reports (AP/Arizona Daily Star, 11/7). The measure, which was approved by a House-Senate conference committee, includes increases in funding for the Global Fund To Fight AIDS, Tuberculosis and Malaria and the Ryan White Program, CQ HealthBeat reports.

The bill would provide $300 million in funding for the Global Fund, up from $99 million for the Global Fund included in the Labor-HHS-Education appropriations bill for FY 2007. Additional U.S. funding for the Global Fund is provided through foreign aid appropriations.

The measure also would increase funding for the Ryan White Program by $84 million, including an increase for the AIDS Drug Assistance Program of $33 million (Reichard, CQ HealthBeat, 11/6). ADAPs are federal- and state-funded programs that provide HIV/AIDS-related medications to low-income, uninsured and underinsured HIV-positive individuals (Kaiser Daily HIV/AIDS Report, 10/10).

The Senate is expected to vote on the legislation on Wednesday. According to CQ Today, Sen. Kay Bailey Hutchison (R-Texas) will lead a Republican attempt to split the legislation back into two bills, which if successful, would send the Labor-HHS-Education measure back to the House. Senate Democrats need 60 votes to keep the bills together, CQ Today reports. Senate Majority Leader Harry Reid (D-Nev.) said if the bills are split, Congress will send the Labor-HHS-Education bill by itself to President Bush.

Bush has said he would veto the Labor-HHS-Education bill by itself or as part of the conference report, if passed by the Senate (Wayne, CQ Today, 11/6). The Labor-HHS-Education bill contains $10 billion more in discretionary spending than the Bush administration requested (AP/Arizona Daily Star, 11/7).

AIDS Vaccine

Merck's Experimental AIDS Vaccine Fails

By LINDA A. JOHNSON – Sep 22, 2007

TRENTON, N.J. (AP) — In a disappointing setback, a promising experimental AIDS vaccine failed to work in a large international test, leading the developer to halt the study. Merck & Co. said Friday that it is ending enrollment and vaccination of volunteers in the study, which was partly funded by the National Institutes of Health.

It was a high-profile failure in the daunting quest to develop a vaccine to prevent AIDS. Merck's vaccine was the farthest along and was closely watched by experts in the field.

Officials at the company, based in Whitehouse Station, N.J., said 24 of 741 volunteers who got the vaccine in one segment of the experiment later became infected with HIV, the virus that causes AIDS. In a comparison group of volunteers who got dummy shots, 21 of 762 participants also became infected.

"It's very disappointing news," said Keith Gottesdiener, head of Merck's clinical infectious disease and vaccine research group. "A major effort to develop a vaccine for HIV really did not deliver on the promise."

Michael Zwick, an HIV researcher at Scripps Research Institute, said the vaccine's failure is unfortunate. But he said it's too soon to know if other vaccines using the same strategy would also fail.

"It's par for the course in the HIV field," he said of the Merck result.

The volunteers in the experiment were all free of HIV at the start. But they were at high risk for getting the virus: Most were homosexual men or female sex workers. They were all repeatedly counseled about how to reduce their risk of HIV infections, including use of condoms, according to Merck.

In a statement, the NIH said a data safety monitoring board, reviewing interim results, found the vaccine did not prevent HIV infection. Nor did it limit severity of the disease "in those who become infected with HIV as a result of their own behaviors that exposed them to the virus" — another goal of the study.

Merck's was the first major test of a new strategy to prevent HIV infection. The first wave of attempts to develop a vaccine tried to stimulate antibodies against the virus, but that hasn't worked so far.

The new effort — an approach that Gottesdiener said is being tried in most other current research — is aimed at making the body produce more of a crucial immune cell called killer T cells. The goal is to simultaneously "train" those cells, like an army, to quickly recognize and destroy the AIDS virus when it enters cells in the bloodstream.

Zwick said some researchers still are working on vaccines to neutralize the AIDS virus. He thinks ultimately what's needed is one that combines that approach with a way to stimulate and train killer T cells.

Merck and the HIV Vaccine Trials Network, an international collaboration of researchers and institutions funded by the NIH, co-sponsored the study. The experiment, called STEP, began in December 2004 and had enrolled 3,000 volunteers in Australia, Brazil, Canada, the Dominican Republic, Haiti, Jamaica, Peru, Puerto Rico and the United States.

The results announced Friday involved volunteers who researchers thought would benefit most because they had never been exposed to the particular cold virus used in the vaccine.

Wall Street, on a generally upbeat day, showed little reaction to the news, with Merck shares rising 44 cents to $51.82.

Analyst Steve Brozak of WBB Securities said the vaccine was considered the most promising candidate both by Wall Street and the science community. He said a vaccine is the only financially feasible way to fight the AIDS epidemic in poor countries and that the company that comes up with the first successful shot would have "a license to print money."

"You're talking about a Carl Sagan kind of number — billions and billions" of dollars, he said.

The Merck vaccine, known only as V520, also was being tested in a similar study in South Africa and in two smaller studies, which also were halted.

The Merck vaccine failure is a "deep disappointment and a scientific setback for the AIDS vaccine field," the AIDS Vaccine Advocacy Coalition said in a statement. However, the nonprofit group added that "while this is a disappointment, it is in no way the end of the search for an AIDS vaccine."

((Considering that the vaccine has failed, there are still several viable and inexpensive treatment options available at AIDS Drugs Online))