|When is the best time to start treatment?
Feb 24, 2004
When is the best time to start treatment?
| Response from Dr. Pierone
When is the best time to start treatment?
The treatment guidelines regarding HIV may be found at this link. Here one can find the rationale for antiretroviral treatment, the references, and ideas about when to start treatment.
Here is the first portion of the guidelines regarding treatment initiation: "Although randomized clinical trials provide strong evidence for treating patients with < 200 CD4+ T cells/mm3 (AI) [35-37], the optimal time to initiate antiretroviral therapy among asymptomatic patients with CD4+ T cell counts > 200 cells/mm3 is unknown."
So the short answer to the question based on hard scientific evidence is that one should start treatment for those with no symptoms when CD4 drops below 200. What about those with more than 200 CD4 cells?
Here is the framework of the long answer from the guidelines: Potential benefits of early therapy include: 1. earlier suppression of viral replication; 2. preservation of immune function; 3. prolongation of disease-free survival; 4. lower risk of resistance with complete viral suppression; and 5. possible decrease in the risk for viral transmission. Potential risks of early therapy include: 1. the adverse effects of the drugs on quality of life 2. the inconvenience of some of the available regimens, leading to reduced adherence; 3. development of drug resistance because of suboptimal suppression of viral replication; 4. limitation of future treatment options as a result of premature cycling of available drugs; 5. the risk of transmission of virus resistant to antiretroviral drugs; 6. serious toxicities associated with certain antiretroviral drugs; and 7. the unknown durability of effect of available therapies. Potential benefits of delayed therapy include: 1. avoidance of treatment-related negative effects on quality of life and drug-related toxicities; 2. preservation of treatment options; and 3. delay in the development of drug resistance. Potential risks of delayed therapy include: 1. the possibility that damage to the immune system, which might otherwise be salvaged by earlier therapy, is irreversible; 2. the possibility that suppression of viral replication might be more difficult at a later stage of disease; and 3. the increased risk for HIV transmission to others during a longer untreated period. As these above points illustrate, there are pros and cons to antiretroviral treatment and any clinician and patient team must consider these issues in formulating a specific treatment plan.
Many people start developing a variety of HIV-related symptoms in the 200 to 350 CD4 count range (some with higher counts too). These may include skin rashes, fatigue, oral thrush, swollen lymph nodes, night sweats, vaginal yeast infections, and more frequent herpes recurrences. These symptoms typically get better when HIV treatment is commenced and viral replication comes under control and CD4 counts improve. So these "minor problems" of HIV infection tilt the balance towards treatment in those patients that suffer with them.
There are observational cohort studies that indicate HIV treatment in the 200-350 CD4 count range may forestall progression to opportunistic infections and death. These data are not definitive, but suggestive of benefit and provides the rationale for starting treatment at a 350 CD4 threshold. So, for CD4 count between 200 and 350 the guidelines state "treatment should be offered, although controversial".
Above 350 CD4 cells there may also be a role for treatment in those patients with high viral load (above 55,000 copies/mL). This is based on relatively greater risk of progression to AIDS and death in those patients with higher levels of replicating virus. Again, no definitive data proving effectiveness of early treatment in this situation, but it may be a sensible approach for an individual to consider.
The current framework of recommendations is based on the premise that treatment is begun when a target threshold is broken by declining CD4 cells (and to a lesser extent high viral load). At this point (whatever that point turns out to be), treatment is commenced and continued for the lifetime of the individual.
This simple model will be revised in the future as our understanding of treatment-related issues advances. Perhaps the future model of HIV treatment is that therapy is commenced when CD4 count drops below 500 CD4 cells and then stopped after the count increases to above 800. After some period of time (1-3 years?) and CD4 count drops below 500, treatment is restarted and then again discontinued above 800. This is known as a CD4 count-driven approach to treatment. Although there is no long-term data supporting this approach, studies are underway using different cut-offs for starting and stopping therapy.
The largest is the SMART study, and is one quarter of the way towards the goal of enrolling 6000 patients worldwide. This is a randomized study that compares the strategy of continuous treatment of HIV infection (primary goal -viral suppression) with the CD4 count driven approach mentioned above.
This question of when to start treatment must be paired with the important question of when to stop treatment. Unfortunately, no definitive answers for either of these questions, so stay tuned!
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