When to start treatment?
New US guidelines released just last week recommend treatment for all people with HIV infection. Are they a step in the right direction, something that others should consider following? Bob Leahy reports.
Newly updated US treatment guidelines are recommending antiretroviral treatment for all people with HIV infection, rather than starting at a particular CD4 range. But for those about to start treatment and their doctors, it’s not quite that simple; the strength of the recommendations varies by category of patient. Here is how a simplified scale looks:
- CD4 count less than 350 – strong recommendation
- CD4 count 350 to 500 - strong recommendation
- CD4 count over 500 – moderate recommendation
Regardless of CD4 count, initiation of ART is strongly recommended for individuals with the following conditions: pregnancy, a history that includes an AIDS-defining illness, HIV-related kidney disease and HIV/hepatitis B virus (HBV) co-infection. The guidelines also include an early treatment recommendation for anyone at risk of transmitting HIV to partners.
In contrast, recently issued draft British HIV Association treatment guidelines continue to recommend treatment when the CD4 cell count falls below 350, although treatment may be started earlier in people with hepatitis B or by people concerned about the risk of transmitting HIV to partners.
Canada has no national guidelines at present, a reflection of our provincially administered healthcare system, but our practice tends to follow the US guidelines. BC and Quebec have their own guidelines. But it’s likely that these new US guidelines will be influential in affecting treatment decisions here and around the world.
In Ontario, the advice you will receive currently depends, at least to some extent, on who is your doctor. Some (many?) doctors are now suggesting treatment immediately on diagnosis, with the consent of the patient, of course. Others are suggesting holding off. But clearly there has been a move towards earlier treatment for some time, driven in part by the evidence of better clinical outcomes for those who start earlier, and in part perhaps by concerns about the perceived need to curb secondary infections that the treatment as prevention advocates frequently cite. More on that later.
The issue of when to start treatment has been controversial. Previously, for instance, the panel that decided on the US guidelines was divided.
There has been little reaction to the new US guidelines from the Canadian HIV community to date. But HIVers from Australia, in the form of NAPWA (National Association of People Living with HIV/AIDS) were quick to state their position. In a March 28 statement, NAPWA president Robert Mitchell said “It is increasingly clear that untreated infection is bad for the health of people living with HIV, whether their infection is recent or long-term. We also think that people with HIV will value the added benefit of being on treatment in helping reduce the risk of transmitting HIV to others, when used with other proven prevention measures like correct and consistent condom use.”
This two-pronged rationale for earlier treatment contains elements which have been troublesome for people living with HIV in the past. Over the years, there have for instance been issues raised about the potential side effects from long(er) term exposure to HIV drugs - longer term at least than if treatment were delayed. Informed consent has also been an issue for some HIVers – nobody wants to be persuaded to start treatment when they are not ready for making that decision. But on this latter point the new guidelines are clear; “patients (who start) ART should be willing and able to commit to treatment and should understand the benefits and risks of therapy and the importance of adherence. Patients may choose to postpone therapy, and providers, on a case-by-case basis, may elect to defer therapy on the basis of clinical and/or psychosocial factors.”
The longer-term exposure to side effects concerns? I raised this issue with Dr Julio Montaner, a long-time early-treatment proponent, when I interviewed him for PositiveLite.com earlier this year. Here’s what he had to say about that. “There is no doubt that antiretroviral therapies have improved dramatically. They are simpler, safer and better tolerated. No doubt about it. Are they perfect? No they are not….However, if we are having a discussion here on whether starting treatment immediately or on a deferred basis, the gap between those two decisions is somewhere in the order of months to a couple of years. It varies from person to person but when we’ve done studies, the rate of CD4 decline in an untreated person is somewhere between 60 and 120 cells per year. If somebody today says ‘no, I’m going to wait,’ what I say is ‘sure, you can defer antiretroviral therapy, no problem, we are not forcing anybody to start treatment.’ What we are saying is let’s have a discussion."
For an expert narrative on the new US guidelines, I interviewed CATIE’s Sean Hosein last week. He’s an acknowledged expert on treatment issues and I wanted to gauge his feelings on the impact of the new guidelines for Canada.
Sean cautions against interpreting the guidelines as saying that once people are diagnosed they should start treatment then and there. “What this means” he says ”is that there is an opportunity for doctors and people living with HIV to start the discussion about therapy. Given the therapy that we have today, people are going to be taking it every day for the rest of their lives, and so people have to be prepared for this – ready, willing and able.”
Do the new treatment guidelines represent a major change? Sean thinks so. ”It’s a major change compared to ten years ago, even five years ago, when they were saying ‘let’s wait ‘til the CD4 counts fall’. But what’s happened is that they’re finding that HIV just doesn’t affect CD4 counts. It causes inflammation inside the body that affects major organs like the brain, the heart, the lungs, the kidneys, the liver, the bones - and so that’s why there is a push to start treatment earlier.”
I asked Sean to what extent the treatment as prevention arguments – which revolve around, in part, reducing the possibility of secondary infections by suppressing viral load to undetectable levels – might have had on the US decision to recommend starting treatment earlier. “I think it’s a mix of two things”, says Sean of the new guidelines. “It’s a mix of trying to do the right thing for the individual person living with HIV and also trying to do something for the rest of society in order to reduce the risk of transmissions.” But of treatment as prevention, Sean cites the cautions in the guidelines about interpreting HPTN 052 results (the much-publicized study released last year which saw a 96% reduction in the risk of HIV transmission in heterosexual sero-discordant couples) too broadly, noting in particular the lack of data relating to MSM (men whoi have sex with men) , an issue discussed in my interview with CATIE’s James Wilton that you can read here.
On the side effects issue, Sean says the environment has changed. ”That argument, I think was important in the 1990’s and maybe ten years ago when the drugs that were used were much less tolerable. With the drugs that are commonly prescribed today, the regimes are simpler. There are side effects but they are generally mild and they tend to go away. It’s true that people haven’t been on the latest drugs for fifty years so in theory there may be problems in years to come. . . . We need long-term studies to monitor people and those studies are underway.”
I asked Sean if the new guidelines are big news for the HIV community. Sean thinks so. “It’s about strengthening doctor/patient relationships. I would encourage people who have recently been tested to see this as an opportunity to speak to their doctor about starting treatment early.”
Does he think the US guidelines will shift the Canadian response to HIV infection? Says Sean “I think it will, because it’s good for people living with HIV. It will keep them alive longer. It’s a good thing.”
I think so too. Starting treatment earlier is likely a good thing for many people. Whether the new US guidelines are driven by a desire for better clinical outcomes for people living with HIV or reflect treatment as prevention policies, or both, is almost immaterial. I say almost because many of us have been vocal about our concerns surrounding treatment as prevention and we are cautious when some of its key tenets appear to go main-stream. But things have changed. Our knowledge of disease progression has changed. Treatments have changed. My own opinions have changed. So yes, I’m with the US on this one.
Let’s hope that Canada follows suit.
- Tags: 2012, AIDS, April 2012, ART, benefits of staring HIV treatment earlyly, Bob Leahy, Canadian HIV treatment guidelines, CATIE, HIV, HIV prevention, HIV+ HIV-positive, HPTN Study 052, impact of undetectable viral load, inflammation and HIV, Interview with Dr Julio Montaner, James Wilton, NAPWA, opposition to treatment as prevention, PositiveLite_com, Sean Hosein, side effects from HIV medications, treatment as prevention, US HIV treatment guidelines