I have to admit that I was skeptical. Starting in 2008, there was increasing evidence that treating HIV-positive people decreased viral transmission in the population. There was increasing discussion of inflammatory markers and the role that inflammation might play in HIV. The idea was also expressed that everyone was going to need drugs in a few years anyway, so why not move it up? I didn't buy it. I failed to see clear-cut evidence of benefit over 500 CD4s and I did not see how to convince individual patients that there were benefits for them in the idea that lowering their viral loads served the public good. Many drugs still had significant side effects, we had seen the difficulties when patients developed resistance and had few options, and the last time we pushed the starting line higher it had not been a good idea. This was a very uncomfortable place for me to be -- it was the first time I had ever found myself thinking more conservatively than the guidelines panel. I wondered if I had been at this too long.
Over the last couple of years the lines of thinking mentioned above have become more firmly established and the evidence for them continues to grow. Rates of HIV infection in the U.S. have continued at the same levels for almost two decades now. In my own practice, I have seen so many young men become positive in the past two years. We have seen high rates of STDs for years, but much of it seemed to be coming from oral sex. In the last two years, I have seen more anal gonorrhea and Chlamydia than I remember seeing in a long time. Some men are looking for any excuse to stop using condoms, the most effective method we have of preventing transmission for people having sex (although pre-exposure prophylaxis, PrEP, adds another tool). It has become very clear that our prevention messages are failing to help people maintain changes in behavior that would lower transmission rates. For young people today, the horrors of the AIDS epidemic are just things they learn about in history books, and the fear of HIV doesn't last beyond the next hook-up. The right wing in the U.S. has destroyed sex education in many places and the level of ignorance about STDs is appalling.
The CDC and other public health authorities have undertaken a powerful campaign for treatment as prevention. I think it becomes increasingly clear that reducing viral load across communities by treating as many people as possible may be our only real chance of bringing this epidemic under control. So government is clearly moving to support universal treatment, thus guaranteeing coverage and access, removing another obstacle on the "con" side of the argument.
As a primary care provider however, one has to be able to convince the patient that the therapy being offered is of benefit to him or her. For those in a relationship with someone of the opposite serostatus, treatment as prevention does serve the interest of increasing the chance that the negative partner will stay uninfected. But the reality is that we are experiencing a new kind of apartheid based on viral load status. Over and over I hear from patients that they are questioned by potential partners about their viral load. If they are on meds and undetectable, they are acceptable sex partners. If they are not on meds, they get rejected. This has pushed some to start therapy earlier.
For real personal benefits to be seen, however, powerful trends needed to come into play. First has been the development of truly tolerable and easy-to-take medication regimens. We have had Atripla for quite a few years now and its once-daily dosing made it easy. But many people still experienced side effects. The development of more once-daily regimens, of two more once-daily fixed dose combinations, the approval of several twice-daily, well tolerated meds in new classes -- all of these have suddenly presented us with more options, not just for initial therapy but for sequential regimens as well. And we expect to see a number of new once-daily and fixed dose combinations in new formulations -- PIs and entry inhibitors without nucleosides, new integrase inhibitors with next generation nukes, and many others. This is truly the first time in fighting HIV that, as a provider, I can say to a patient that he or she will most likely not have any side effects from the medication I'm prescribing.
The third area of growing consensus has been in regard to the importance of inflammation as a cause of disease. This is a trend across the entire field of medicine. Inflammation appears to play important roles in aging, in the development of cardiovascular disease, in neurologic disease, as well as in rheumatology, endocrinology, and virtually every other area. People with HIV at every CD4 count have shown elevated levels of inflammation and immune activation, as well as heightened risk for a myriad of diseases from blood clots to early heart attacks. By the time of the International AIDS Conference in Washington, D.C. last year, the evidence for the deleterious effects of inflammation and the positive impact of ART on markers of immune activation was becoming overwhelming. Data continues to accumulate rapidly. As I wrote this article, two new studies appeared in the New England Journal of Medicine which showed significant benefit for patients started on medications very early in the disease process.
The 2012 guidelines gave a stronger recommendation than previously to treating all patients with fewer than 500 CD4/mm3. There also appeared to be a growing consensus of expert opinion leading to more universal treatment.
For me, the meeting in D.C. brought a kind of epiphany. It finally seemed that the scales had shifted. The things on the negative side of the scale -- the side effects, complicated regimens, drug access issues, and lack of documented benefit -- seemed to be lightening if not absent. And the side of the scale in favor of treatment was becoming heavier and heavier with reasons to start early. In fact, it appears to me that it is time to jump off of the swing at the highest point of its arc, to stop using CD4 count as a parameter in deciding when to start, and to offer treatment to all patients who are infected with HIV. I have begun to do this with overwhelming acceptance by many of my patients. Hopefully, we'll land on our feet.