A new category of drug has shown promising results for HIV/AIDS patients who failed to respond to other treatments, a study to be published Saturday shows.

Especially when combined with other medications, raltegravir -- the first in a new class of anti-retroviral drugs called integrase inhibitors -- dramatically reduced the presence of the HIV virus and boosted immunity in clinical-trial patients, according to the study in the British journal The Lancet.

Integrase inhibitors act by targeting and disrupting an enzyme that facilitates the insertion of the HIV virus into the host's cellular genome.

In clinical tests on 178 patients with advanced HIV infections that had proved resistant to standard treatments, raltegravir "showed unprecedented levels of virological efficiency," virologists Pedro Cahn and Omar Sued wrote in a commentary in the same journal.

The treatment "achieved virological suppression even in patients with limited options," they wrote, predicting that the new drug would "have a major role in salvage therapy," the term used to describe last-ditch efforts to save those with highly-compromised immune systems.

"Clearly, we are in a new era of anti-retroviral therapy," they added.

There are three types of enzyme needed for HIV to replicate, namely reverse-transcriptase, protease and integrase. Up to now, no drug has successfully inhibited integrase enzymes.

A team of researchers at Merck Research Laboratories in Westpoint, Pennsylvania, led by Beatriz Grinsztejn, divided the 178 patients into four groups during clinical trials.

Each of three groups were given different doses of raltegravir, ranging from 200 to 600 milligrams, and the fourth group received a placebo. All four also took a basic "background treatment."

After 24 weeks, the amount of HIV genetic material in the blood dropped below a measurable threshold (50 copies per millilitre) in 65 percent of the patients taking raltegravir, nearly five times as many as the placebo group. Immune system responses were also dramatically improved.

"If no long-term unexpected side-effects or resistance issues emerge, raltegravir will have a major role in salvage therapy, particularly in combination with another new drug," Cahn and Sued concluded

The sexually transmitted disease gonorrhea is now among the "superbugs" resistant to common antibiotics, leading U.S. health officials to recommend wider use of a different class of drugs to avert a public health crisis.

The resistant form accounts for more than one in every four gonorrhea cases among heterosexual men in Philadelphia and nearly that many in San Francisco, according to a survey that led to Thursday's recommendation by the Centers for Disease Control and Prevention.

Gonorrhea, which is believed to infect more than 700,000 people in the United States each year, can leave both men and women infertile and puts people at higher risk of getting the AIDS virus.

Since the early 1990s, a class of drugs known as fluoroquinolones has provided a relatively easy cure. These antibiotics, taken as tablets, include the drug Cipro.

But a growing number of gonorrhea cases is resistant to those drugs, and officials at the CDC for the first time are urging doctors to stop using fluoroquinolones and switch to cephalosporins, a different class of antibiotics, to treat everyone.

Those drugs — which include the generic ceftriaxone or brand name Rocephin, made by Swiss drug maker Roche Holding AG — must be given as a shot and aren't as readily stocked as Cipro on most doctor's shelves.

"Gonorrhea has now joined the list of other superbugs for which treatment options have become dangerously few," said Dr. Henry Masur, president of the Infectious Disease Society of America. "To make a bad problem even worse, we're also seeing a decline in the development of new antibiotics to treat these infections."

The CDC made the new recommendation after discovering that nearly 7 percent of gonorrhea cases among heterosexual men in a survey of 26 U.S. cities last year were drug-resistant. In 2001, only about 0.6 percent of gonorrhea cases among heterosexual men were drug-resistant.

"That leaves us with a single class of highly effective antibiotics," said Dr. John Douglas Jr., director of the CDC's division of STD prevention. Other experts called the situation perilous.

"We are running out of options to treat this disease," added Douglas, who said there are "no new drugs for gonorrhea in the drug development pipeline."

Previously, CDC recommended against fluoroquinolones to treat drug-resistant gonorrhea among men who have sex with men and in certain states, including California and Hawaii where most of these cases were turning up.

Described by Douglas as a "very wily" disease, gonorrhea has worked its way through decades of other treatment regimens, from sulfa drugs used in the 1930s and 1940s, to penicillin, which was used from the 1940s until the mid-1980s.

Gonorrhea, spread through sexual contact, is the second most commonly reported infectious disease in the United States, trailing only chlamydia, which the CDC says affects more than 2.1 million people yearly in the U.S.

The highest rates of infection are among sexually active teens, young adults and African-Americans. Because many people don't have obvious symptoms, they can unknowingly spread it to others. And having it makes people more susceptible to HIV. Gonorrhea's spread is preventable through consistent and proper use of condoms, experts said.

In women, the infection can cause pelvic inflammatory disease. In men, it can cause epididymitis, a painful condition of the testicles that can lead to infertility if untreated, the CDC said.

In the survey of gonorrhea cases among heterosexual men in 26 cities last year, Philadelphia had the highest percentage of drug-resistant cases with almost 27 percent, a dramatic increase from only 1.2 percent in 2004.

San Francisco's drug-resistant cases more than doubled between 2004 and 2006, from 10.3 percent to 22.5 percent. During the same period, Miami's cases spiked from 2.1 percent to 15.3 percent and Atlanta's climbed from 1 percent to 5.7 percent.

The launch of new drugs and an increase in the number of people diagnosed with HIV is set to make AIDS medicine a $10.6 billion market by 2015, according to a report on Thursday.

Drugmakers may be under pressure to cut prices in the developing world but selling HIV drugs in the West remains a lucrative and fast-growing business.

Independent market research firm Datamonitor said the HIV/AIDS market was set to undergo significant changes over the next 10 years as drugs that work through novel mechanisms and next-generation versions of existing drugs are launched.

Sales, as a result, should rise significantly from about $7.1 billion in 2005, benefiting a clutch of companies with promising new products, including Merck & Co Inc., Pfizer Inc., Gilead Sciences Inc. and Johnson & Johnson.

Most cases of HIV/AIDS occur in sub-Saharan Africa, where lack of funding means treatment is restricted and prices are under pressure, resulting in little if any profit for multinational drug firms.

Just this week Abbott Laboratories Inc., widely criticized for aggressive pricing of its AIDS medicines, agreed to slash the price of its Kaletra AIDS drug by more than half in more than 40 poor countries.

But at the same time the disease is also increasing in the developed world, with an estimated 2.1 million people in North America and Western Europe living with HIV in 2006, up from 1.9 million in 2004.

"Advances in antiretroviral therapy have turned HIV from a universally feared death sentence into a chronic disease with an average life expectancy similar to that of Type 2 diabetes," Datamonitor analyst Mansi Shah said.

"Because of this, attitudes towards HIV have become relatively blase amongst some groups."

Notable new types of drugs include Pfizer's maraviroc, a CCR5 inhibitor, and Merck's raltegravir, an integrase inhibitor, which are expected to be launched in 2007 and 2008 respectively.

They will complement new generation forms of existing drug classes, such as Johnson & Johnson's recently approved Prezista, a protease inhibitor.

Such products offer new treatment options for the growing number of patients whose disease no longer responds to existing drugs.

At the same time, other companies are developing improved fixed-dose drug combinations, including Atripla from Gilead, which combines the components of current drug cocktails into a single pill that can be taken once a day.

Atripla was launched in the United States last year and is expected to take market share from its two components Truvada and Sustiva, as well as competitor drugs such as GlaxoSmithKline Plc's Combivir, Datamonitor said.

The global market for all pharmaceuticals grew 7 percent last year to $643 billion, according to estimates from another market research company, IMS Health, released last month.

Abbott Laboratories Inc., widely criticized for aggressive pricing of its AIDS medicines in developing countries, said on Tuesday it would slash the price of a key AIDS drug by more than half in more than 40 poor countries.

Abbott said it would offer its drug Kaletra at a price of $1,000 per patient per year -- a price lower than generic versions -- to governments of more than 40 countries with low and low-middle income, as defined by World Bank criteria.

The move is an apparent attempt to cool tensions with its critics, amid a spat with the government of Thailand over AIDS drug pricing.

The company has had a worse-than-average reputation with AIDS patient groups, notably after a 400 percent price hike it set a few years ago for another AIDS drug. Advocates were mixed on the significance of the Kaletra announcement.

"Abbott was the most hard-nosed opponent we faced in a very long time," said Michael Weinstein, president of the AIDS Healthcare Foundation, which runs treatment clinics in the developing world. He called the move "an historic victory" for AIDS activists.

But another prominent patient group and provider of medicines said it was too early to declare victory, because an announced price cut does not always translate to real availability of medicines.

"We've seen these announcements before that haven't really led to anything -- particularly in this way, when it is done as a result of pressure from civil society and other groups," Dr. Buddhima Lokuge, U.S. manager for Doctors Without Borders, said.

Several weeks ago, Abbott said it would stop launching new drugs in Thailand, including an important new AIDS drug, to protest the Thai government's decision in January to override international drug patents. The Abbott announcement sparked protests from AIDS advocates.

Lokuge said earlier announcements on price breaks didn't always translate into medicines on the ground, in part because the company didn't register the drug in certain countries.

Kaletra, the most widely used of a type of AIDS medicines called protease inhibitors, is especially effective in patients who have become resistant to HIV, the virus that causes AIDS.

"With this action, we've removed HIV pricing from the debate," Abbott spokeswoman Melissa Brotz said. "We hope there will be a constructive, thoughtful debate on the real issue: how to continue to enhance affordability of medicines and preserve a system that society needs to continue to bring forward new medicines."

World Health Organization director-general Margaret Chan welcomed the price cut.

"We are seeing many more patients develop resistance to first-line antiretroviral drugs who will require second-line drugs," she said. "Clearly a high number of people in 40 countries will benefit."

The dispute with Thailand continues, and the company said it still refuses to offer a newer form of Kaletra called Aluvia in Thailand.

AIDS activists widely criticized the blocking of Aluvia, because it is a heat-stable form of Kaletra, eliminating the need for costly cold storage in resource-poor countries.

In 2003, Abbott raised the price of another AIDS medicine called Norvir by 400 percent, sparking protests, including one at its annual meeting.

British investigators describe 20 cases of humans being infected with Mycobacterium bovis, a type of tuberculosis normally confined to cattle. In six instances, the outbreak appears to have resulted from person-to-person transmission.

This report "emphasizes the need to maintain control measures for human and bovine tuberculosis," Dr. Jason T. Evans, from the West Midlands Public Health Laboratory in Birmingham, UK, and colleagues note in The Lancet medical journal. "Transmission and subsequent disease was probably due to a combination of host and environmental factors."

The researchers performed DNA fingerprinting of all tuberculosis cases that arose in central England between 2001 and 2005. Of the 20 cases that were due to M. bovis, a cluster of six were genetically identical.

All six cases involved young, UK-born individuals, the report indicates. The infection involved the lungs in five patients and caused meningitis in one patient, who died.

The patients had shared social links through bars in two areas. The lack of contact with animals or dairy consumption in all but one of the individuals helped make the case for person-to-person transmission of the infection.

In a related editorial, Dr. Charles O. Thoen, from Iowa State University in Ames, and Dr. Philip A. LoBue, from the Centers for Disease Control and Prevention in Atlanta, comment that "investigations are needed to elucidate the relative importance of M. bovis in the worldwide tuberculosis problem in human beings, especially in developing countries."

Special focus should be paid to countries with widespread HIV infection, since it raises the risk of M. bovis infection, they add.

SOURCE: Lancet, April 14, 2007.