Study confirms that the sooner treatment is started the better

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A study presented at the Tenth International Congress on Drug Therapy in HIV Infection (HIV10) in Glasgow has found that patients who started antiretroviral combination therapy (cART) within the first year after diagnosis were 36% less likely to experience treatment failure, and 65% less likely to develop HIV drug resistance on treatment, than patients in general.

The patients studied were in CASCADE, a unified ‘cohort of cohorts’ in 13 European countries, Australia, Canada and several countries in Africa. CASCADE, which stands for Concerted Action from Seroconversion to AIDS and Death in Europe, only includes patients with a known date of HIV infection (seroconversion). The current study examined the clinical history of 1223 patients who had started cART less than a year after seroconversion and included patients from 1997 onwards: it therefore included many patients who had started on what would now be regarded as suboptimal regimens.

The primary outcomes studied were the proportion of patients who developed virological treatment failure (defined as at least two consecutive viral load tests over 400 on treatment) and the proportion who developed HIV drug resistance.

Glossary

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

treatment failure

Inability of a medical therapy to achieve the desired results. 

seroconversion

The transition period from infection with HIV to the detectable presence of HIV antibodies in the blood. When seroconversion occurs (usually within a few weeks of infection), the result of an HIV antibody test changes from HIV negative to HIV positive. Seroconversion may be accompanied with flu-like symptoms.

 

tolerability

Term used to indicate how well a particular drug is tolerated when taken by people at the usual dosage. Good tolerability means that drug side-effects do not cause people to stop using the drug.

naïve

In HIV, an individual who is ‘treatment naïve’ has never taken anti-HIV treatment before.

Of the 1223 patients, 85% were male, with a median age of 34. Their average CD4 count at the start of therapy was 432; a majority would have been excluded from starting therapy if doctors had conformed to the recommendations of the current BHIVA and EACS treatment guidelines, though not US ones.

One hundred and fifty-one patients had drug resistance tests before they started cART, and seven patients (4.6%) turned out to have primary (transmitted) drug resistance.

The fact that this is a historical cohort was underlined by the fact that 71% started on protease-inhibitor-based cART. Sixty per cent interrupted their therapy at some point and the average time to interruption of therapy was one year.

In terms of time to virological failure, by four years after the start of therapy 11% had experienced failure and 3% (of the whole group) had confirmed drug resistance that had been detected. This latter figure may be higher in truth, because only half of the patients who failed had drug resistance tests.

Eight years after the start of therapy, 18% had failed treatment and 6% had confirmed drug resistance. These figures are lower than those seen in a survey of the long-term treatment history of a cohort of all patients on treatment (Cozzi-Lepri): in this study, after eight years, 28% had failed treatment and 17% had confirmed drug resistance.

Presenter Sara Lodi commented that most failures happened in the first two years of treatment. The older people were when they were diagnosed and started treatment, the less likely they were to fail treatment: there was 30% less treatment failure for every decade of age. And there was 8% less failure and 26% less drug resistance for every 100-cell increase in CD4 count at the start of treatment.

Delegates were reminded that HIV treatments became considerably more effective and tolerable over the time period surveyed in the study. One reminder was that patients who had taken unboosted protease inhibitor regimens were nearly three times (192%) more likely to have failed treatment than patients with other treatment histories.

Lodi’s cautious conclusion was that: “Our data do not support early initiation of antiretrovirals being associated with high levels of drug resistance.”

References

Lodi S et al. Long-term probability of detecting drug-resistant HIV in patients starting antiretroviral therapy within the first year of HIV infection. Tenth International Congress on Drug Therapy in HIV Infection in Glasgow, abstract O114, 2010.

Cozzi-Lepri A et al. Long-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy. Clinical Infectious Diseases 50(9): 1275-1285, 2010.