Extensive HIV treatment failure found rare

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Extensive HIV treatment failure found rare

Thursday, December 06, 2007

Complete failure of HIV treatment on the basis of the three original drug

classes is much more the exception than the rule. By , North

American Correspondent, MedPage Today reviewed by P. Bamford, MD; Senior

Fellow, Infectious Diseases Division, University of Pennsylvania School of

Medicine.

LONDON, Dec. 6 -- Complete failure of HIV treatment on the basis of

the three original drug classes is much more the exception than the

rule, researchers here said.

The finding may be encouraging for clinicians and patients in

developing countries, where in most cases only drugs from the three

original classes are available, according to , Ph.D.,

of the Royal Free and University College Medical School, and

colleagues.

In a cohort of 7,916 HIV patients in the United Kingdom, only 167

ever developed " extensive " failure to respond to the three classes,

Dr. and colleagues reported in the Dec. 8 issue of The

Lancet.

And even among those, Dr. and colleagues said, there was

enough residual drug activity so that 60% had an undetectable HIV

viral load at least once after they were classified as having

extensive virological failure.

" Extensive " failure was defined more strictly than the usual category

of " triple-class failure, " which is defined simply as failure to

respond to at least one nucleoside reverse transcriptase inhibitor

(NRTI), one non-nucleoside reverse transcriptase inhibitor (NNRTI),

and one protease inhibitor (PI).

" Extensive " failure was defined as:

For nucleoside reverse transcriptase inhibitors, a lack of response to at least

one drug each from three subclasses -- zidovudine or stavudine; lamivudine or

emtricitabine; and didanosine, tenofovir, or abacavir.

For the non-nucleoside reverse transcriptase inhibitors, lack

of response to efavirenz or nevirapine.

For the protease inhibitors, failure of at least one ritonavir-boosted protease

inhibitor. Lack of response -- or " virological failure " -- to a given drug was

defined as a viral load higher than 400 copies of HIV RNA per milliliter of

blood despite four continuous months of therapy with the medication.

Over 27,441 person-years of follow-up, the researchers found

extensive triple-class failure in 167 patients, 90% of them with a

lack of response to seven drugs or more, and 58% of them who went on

to fail second-line therapies.

The only drug outside the three original classes that was available

during the study period was the fusion inhibitor enfuvirtide, but

only five of the 167 patients with extensive triple-class failure

used it. (Three new drug classes are currently available -- fusion

inhibitors, integrase inhibitors, and CCR5 antagonists.)

Despite their relative lack of other options, the five-year risk of

death for patients with extensive triple-class failure was 10.6%,

with a total of nine deaths over the follow-up period.

Over the whole cohort, the 10-year risk for extensive triple-class

failure was 9.2%, but the researchers said that appears to have

decreased over time by roughly 14% per year, which was significant at

P=0.006.

Two factors of importance in the developing world appear to affect

the risk of developing extensive failure, the researchers found in a

multivariate analysis of baseline factors:

Being heterosexual was associated with a doubling of the risk. The odds ratio

was 2.26, with a 95% confidence interval from 1.50 to 3.40, which was

significant at P<00001.

Having a higher CD4 cell count decreased the risk by 32% for

every 100 cells per microliter of blood. The odds ratio was 0.68,

with a 95% confidence interval from 0.60 to 0.77, which was also

significant at P<00001.

Starting treatment with more than 200 cells per microliter gave a

cumulative 10-year risk of extensive triple-class failure of 5.5%,

compared with 12.1% for those who started therapy with a lower CD4

cell count.

Both factors may affect therapy in the developing world, where the

pandemic is largely heterosexual in nature and where a level of 200

CD4 cells is often considered an upper limit for starting therapy.

The good news in the study is that extensive failure was rare,

according to Mills, Ph.D., of the Center for Excellence in

HIV/AIDS in Vancouver, and Nachega, M.D., of s Hopkins

Bloomberg School of Public Health, writing in an accompanying

commentary.

But, they said, the bad news is that many patients then went on to

fail further regimens -- options that are usually not available in

the developing world.

The study " underscores the need for access to alternative, less

toxic, and more affordable first-line, second-line, and now third-

line antiretroviral drugs in developing countries, " they argued.

The study was supported by the Medical Research Council of the United

Kingdom. Dr. reported financial links with Boehringer

Ingelheim, Roche, Abbott, GlaxoKline, Gilead Sciences, Tibotec,

and Janssen-Cilag.

Primary source: The Lancet. Source reference:

AN, et al " Risk of extensive virological failure to the

three original antiretroviral drug classes over long-term follow-up

from the start of therapy in patients with HIV infection: an

observational cohort study " Lancet 2007; 370: 1923-28.

Additional source: The Lancet. Source reference:

Mills E, Nachega J, " A wake-up call for global access to salvage HIV

drug regimens " Lancet 2007; 370: 1885-87.

http://www.medpagetoday.com/HIVAIDS/HIVAIDS/tb/7614