Practical Questions for Women:

The Federal Guidelines for Starting and Switching Therapy

According to the Federal Guidelines, any HIV-positive adult who is not experiencing symptoms and whose CD4+ cell count is less than 500 should be offered therapy. This recommendation is independent of HIV viral load. In other words, regardless of your viral load, if you have a CD4+ cell count of -- let's say -- 475, your doctor may suggest the start of anti-HIV therapy.

Not everyone with CD4+ cell counts below 500 chooses to initiate anti-HIV therapy, nor does every doctor recommend it. Nevertheless, there is sufficient data to say that every patient should be made aware of the option for treatment at this stage. The decision to start treatment, however, will still often take into account such other factors as the broad trends in CD4+ counts and viral load, as well as the patient's overall readiness and willingness to start therapy. There is no data, however, which suggest that patients will fare any better by waiting until later thresholds, such as 350 or 400 CD4+ cells. However, there are data that show that waiting until after CD4+ cell counts fall below 200 is probably harmful because of the risk of opportunistic infections at this level.

In light of these new studies, however, interpreting the Federal Guidelines can get even more complicated. That's because HIV levels above 10,000 copies/ml (see The Basics of Viral Load Testing, below) are used as a supporting factor for initiating therapy according to CD4+ cell count.Yet it is also a factor for initiating therapy independent of CD4+ cell count (even this number, though depends on which brand of viral load test your doctor uses, since one brand tends to read twice as high as the other).

So, if you have a CD4+ cell count of 475 and HIV levels of 6,000 copies/ml, should you start therapy? An aggressive anti-HIV therapy approach would support considering therapy based on your CD4+ cell count alone. A more conservative approach, however, might include postponing the start of therapy until HIV levels rose near or above 10,000 copies/ml or until the CD4+ count declines further.

The rationale behind postponing therapy is that, in addition to being otherwise healthy, your CD4+ cell count has been stable for several tests and your viral load is less than the 10,000 copies/ml threshold. This situation could remain stable for years to come, or it might change rapidly over the next several months. Thus, you and your doctor might decide together to delay beginning therapy and continue careful observation and monitoring to see which pattern you are following.

Now Here's the Catch . . .

According to both of these two new studies, a woman whose CD4+ cell count is 475 and who has a viral load of 6,000 copies/ml is roughly at the same risk of disease progression as a man with a similar CD4+ cell count whose viral load is 10,000 copies/ml. Therefore, a conservative interpretation of the Federal Guidelines as it currently stands would support that a man could start anti-HIV therapy. A woman, on the other hand, according to the current recommendations, could be supported in a decision to wait and not start therapy, when in fact she is at same risk of disease progression as the man in this scenario.

In general, and to the Federal Guidelines committee, these differences appear to be relatively small and don't warrant changing the current recommendations based on gender. In either case, the decision about when to start therapy is a personal one. Choosing to briefly delay therapy is unlikely to make a large difference in long-term results. Based on existing data, both men and women at these stages are only in the early range at which treatment might be recommended. No one would say the decision is critical either way. In truth, at the viral load levels we're talking about, what's probably most important are trends and not absolute numbers. However, this information could be important information to you and your doctor as you evaluate the best strategy for your own situation.

As with the initiation of anti-HIV therapy, the decision to change therapies is approached with consideration of several factors. Among these factors are HIV viral levels measured on two separate occasions; CD4+ cell count; tolerance of and adherence to the current regimen; and overall general health.

The goal of anti-HIV therapy -- to improve the length and quality of life for persons living with HIV -- is thought best accomplished by suppressing viral load to below detectable levels for as long as possible while preserving immune function. Again, an aggressive anti-HIV therapy approach supports possibly changing anti-HIV therapy regimens whenever viral load is consistently in the detectable range of the test (on at least two consecutive tests). In practice, however, the degree of detectability or increase in viral level is usually considered along with a sober assessment of the number of treatment options a patient has left to work with. Persons with low viral levels (e.g. 100-5,000 copies/ml) may choose not to change therapy immediately and simply decide to monitor further changes in viral load, CD4+ cell counts and measures of general health. Some people in this situation will maintain low levels of virus, sometimes dipping below the level of detection and sometimes having sporadic detectable readings.

Again, the new studies give pause to this practice where women are concerned. Low viral load is currently defined at 100-5,000 copies/ml. Should a viral load of 3,000 copies/ml be viewed and responded to in the same way as 5,000 copies/ml in a woman with a CD4+ cell count between 200 and 500? How should this be interpreted in regard to switching therapy? At this point, the answer remains unclear. All existing data about how viral load affects the risk of HIV disease progression comes from natural history studies -- studies of people who have not been treated for the disease. It is not at all clear that a certain viral load level has the same mean-ing after treatment as it did before treatment.

Certainly, these new studies point to the need for further study with regard to viral load in women and related risks of disease progression. These studies also remind us of two other points. CD4+ cell counts provide useful measures of the risk of disease progression, and their meaning is not influenced by gender. Moreover, the decision to start, add or change therapy should never be decided solely on the basis of one laboratory measure (e.g. just viral load, just CD4+ cell counts, etc.). Treatment decisions should factor in trends in viral load; trends in CD4+ cell counts; the number of available future options; side effects; ease of adherence; and measures of overall general health.

While the Federal Guidelines Panel has decided to make no recommendations for a different standard of care for women with HIV, women and their doctors should be aware of these data which may support starting and switching therapy at lower HIV levels than what is recommended for men. A notation to this effect will be put in the revised Guidelines document. Nevertheless, viral load alone is not the only factor to consider when making treatment decisions. Moreover, the differences in viral load between men and women would only impact the treatment decision for women in a very narrow range of viral load and CD4+ cell levels.

Over the next few months, a clearer picture of women and viral load is expected to unfold. WISE Words will continue to report on this new information. In the meantime, keep in mind that more harm than good can be done by making too hasty of choices when starting, switching or stopping anti-HIV therapy. A carefully considered choice regarding therapy is the best one anyone can make. Remember, there is support for you in making that choice.

For your own free copy of the Federal Guidelines (entitled Guidelines for the Use of Anti-HIV Therapy Antiretroviral Agents in HIV-Infected Adults and Adolescents) call: 1-800-458-5231 or 1-800-448-0440. For more information of strategies for anti-HIV therapy, call Project Inform's toll-free National HIV/AIDS Treatment Hotline at 1-800-822-7422 and request Antiviral Strategies Discussion Paper.