Switching Antiretrovirals May Not Enhance HIV Treatment

Pam Harrison

August 08, 2014

MELBOURNE, Australia — For virologically suppressed HIV patients, a switch in antiretroviral therapy is associated with an increased risk for subsequent virologic failure, Canadian Observational Cohort (CANOC) researchers suggest.

"There are good reasons for wanting to switch a treatment regimen," said Marina Klein, MD, from the McGill University Health Centre in Montreal. Most are related to trying to simplify the regimen or to eliminate adverse effects.

It has been presumed that outcomes would be similar after a regimen switch, "but we found that switching regimens while virologically suppressed may not be completely benign," she told Medscape Medical News.

"If someone is doing well, you have to consider the possibility of increased virologic failure if you switch to another regimen," she said.

Dr. Klein presented the study results here at the 20th International AIDS Conference.

The researchers evaluated the risk for virologic failure in 2807 HIV-infected patients from the CANOC collaboration who initiated antiretroviral therapy from January 2005 to June 2012.

CANOC is Canada's largest HIV cohort study. It focuses on evaluating the impact of antiretroviral therapy in people living with HIV across the country.

If someone is doing well, you have to consider the possibility of increased virologic failure if you switch to another regimen.

Everyone in the study cohort had achieved virologic suppression, defined as a viral load below 50 copies/mL measured twice, at least 1 month apart. Virologic failure was defined as a viral load above 1000 copies/mL.

During the study period, 64% of the patients never switched their antiretroviral regimen, 14% switched regimens once, and 22% switched regimens at least twice. Mean time to first switch was approximately 10 months.

Switching therapy was associated with an increased risk for subsequent virologic failure (adjusted hazard ratio, 2.70), the researchers report.

Residents of either Ontario or Quebec were approximately 3 times more likely to have made a single switch than residents of the reference province of British Columbia. However, Ontario and Quebec residents were significantly less likely to have made 2 or more switches than British Columbia residents.

As the duration of antiretroviral therapy increased, the likelihood of switching therapies also increased.

Injection drug users were more likely to have made 2 or more switches.

Surprisingly, males were less likely to have made any switch than females, and were significantly less likely to have made 2 or more switches.

Table. Factors Associated With a Switch in Antiretroviral Therapy

Factor Adjusted Odds Ratio P Value
1 regimen switch    
   Ontario residence (vs BC) 2.84 .001
   Quebec residence (vs BC) 2.86 <.001
   Duration of therapy 1.45 <.001
At least 2 regimen switches    
   Male 0.53 .001
   Injection drug use 1.11 .54
   Ontario residence (vs BC) 0.32 <.001
   Quebec residence (vs BC) 0.48 <.001
   Duration of therapy 1.72 <.001


The fact that there were more switches in women than men might be related to pregnancy, which the researchers could not account for. If a woman was anticipating pregnancy, she may well have switched to a safer regimen for the duration of her pregnancy, Dr. Klein explained.

It could also be that women are more susceptible to certain adverse effects, which has been seen in some studies.

"This was an observational study," she noted. "We did not collect a lot of data on adherence or the precise reasons people were switching, so some of these virologic failures may have simply been people stopping treatment for whatever reason.

"I think it's really important to consider the need for any switch carefully and weigh the risks and benefits," Dr. Klein said. "If a patient is asking to switch regimens frequently, it could be a marker of problems with adherence or poor tolerance. Physicians need to look at those patients carefully to see how they might support them better so that they can take their treatment successfully."

There was a lot of potential for bias in this study, said session cochair Joel Gallant, MD, from the Southwest Care Center in Santa Fe, New Mexico. "My interpretation of the study is that switching was a proxy for patient characteristics that may have been associated with poorer adherence," such as sex and province of residence, Dr. Gallant told Medscape Medical News.

"I don't think we can conclude from this study that a switch itself is the cause of failure. Rather, switching is identifying people who are at risk for failure for other reasons," he said.

The study was supported by a grant from the Fonds de la recherche du Québec, and by Merck and ViiV. Some of the researchers report receiving honoraria and serving as consultants for various pharmaceutical companies, including Merck, ViiV, Gilead, and Janssen. Dr. Gallant reports financial relationships with various pharmaceutical companies, including Merck, Gilead Sciences, Janssen, and Takara Bio.

20th International AIDS Conference: Abstract TUAB0103. Presented July 22, 2014.


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