Understanding the Details of HIV Treatment

When to Start: CD4 Count Ranges

A Brief, Basic Explanation on Clinical Studies

This section mentions two types of studies, both of which can provide important information about HIV disease. Randomized studies are considered the "gold standard" of clinical research. By randomly putting people in different groups or arms, they balance both known and unknown factors as well as limit biases that may influence the outcomes of the study. Observational and cohort studies are less rigorous and do not randomize or control study arms. For example, such a study might look at a group of people who have heart attacks and see what they have in common. While these studies can produce useful information, they may not be able to limit biases or unknown factors to the same degree as randomized studies.

Starting Treatment During Early Infection

There's not as much research on starting HIV drugs in the first few months or even first year of infection. Many, if not most, people do not have to decide this soon after their diagnosis. However, it's reasonable for people to start at this time if they believe it will benefit them. Starting early may prevent damage from HIV, including loss of CD4s and problems related to inflammation.

On the other hand, starting immediately after infection may not give you enough time to fully learn about the risks and benefits of long-term treatment. Starting early risks "using up" HIV medications sooner, as well as long-term side effects and drug resistance.

Starting Treatment at 200 CD4 Cells or Below

The Guidelines state that treatment should be started when CD4s are below 200, which constitutes an AIDS diagnosis. If you're in this range at diagnosis, HIV treatment can greatly improve your health and CD4 count, and help prevent AIDS and other health conditions. Results from several randomized and long-term observational studies clearly show that waiting until CD4s drop below 200 greatly increases the risk of OIs, other health conditions and death. More study results support starting treatment in this CD4 range than at any other level.

Starting Treatment Between 200-350 CD4 Cells

The Guidelines state that treatment should also be started when CD4s are in this range. If you're in this range at diagnosis, HIV treatment can improve your health and CD4 count, and help prevent AIDS and other health conditions. A few randomized studies show more benefit to starting in this range than waiting to start at 200 or below. For example, the CIPRA study showed a significantly higher rate of death and TB in people who started below 200 vs. those who started below 350. Also, a sub-study from the SMART study showed a lower risk of AIDS and non-AIDS conditions in people who started HIV meds with CD4s above 350 vs. those with less than 250 CD4s.

Starting Treatment Between 350-500 CD4 Cells

The Guidelines state that treatment is recommended in this range, although the expert panel was divided on the strength of this recommendation. While the panel agreed that the risk of death or serious illness is low overall, no randomized studies have conclusively shown to start in this range.

Results from some large observational studies suggest benefits to starting in this range. The ART-CC study showed a lower rate of AIDS and death in people with 350–450 CD4s vs. those with 250–350 CD4s. NA-ACCORD and CASCADE showed an in­creased risk of death for people who started treatment below 350 vs. 350–500. What limits these studies is that the overall numbers of AIDS cases and deaths were small. They also didn't evaluate the impact of adherence, resistance or long-term side effects.

Other studies show that starting in this range leads to higher CD4 counts. The ATHENA cohort showed that people who start with CD4s above 350 will more likely reach a level above 800. The John Hopkins cohort showed that those who started at below 350 CD4s are less likely get their count above 500. Further, there's growing evidence to suggest that damage to various organs is possible due to inflammation from untreated HIV at most any CD4 level. Read more about this range in the sections titled "Possible benefits & risks of starting treatment at 350–500 CD4s".

Starting Treatment Above 500 CD4 Cells

In the US, the average CD4 count at diagnosis is about 340. Yet, some people consider starting when their CD4s are above 500. No randomized and few observational studies show an advantage for starting above 500. CASCADE showed a benefit in the 350–500 range but not above 500. Some experts think starting HIV meds above 500 might limit damage to the immune system and organs due to inflammation. The Guidelines panel was split: half favored starting in this range while half thought it was optional. Although it's reasonable for someone to start above 500, the pros and cons should be carefully considered as the risks and benefits are not yet known. The new START study will help answer this question (read the section titled "The START Study").

Possible Benefits of Starting Treatment at 350-500 CD4s

• An increasing number of observational results and early clinical studies suggest lower rates of AIDS and other health related conditions and death.
• Current first line regimens are more effective and easier to take and tolerate, which helps improve adherence.
• People who start above 350 are better able toachieve and maintain higher CD4s over time than those who start below 350.
• People with better overall health tend to have an easier time tolerating medicines.
• Starting in this range reduces the risk of early damage to the immune system.
• Starting in this range reduces, though does not eliminate, inflammation.
• Untreated HIV, even at higher CD4s, may contribute to heart, liver, kidney, brain and other organ diseases and cancers.
• Starting in this range reduces the transmission of HIV, based on several studies of mixed HIV status, heterosexual couples.
• Early treatment may decrease overall cost of health care by avoiding more serious conditions later.

The Possible Risks of Starting Treatment at 350-500 CD4s

• Randomized studies have not been done, which would provide more solid evidence of an added benefit.
• The ART-CC and NA-ACCORD included many people who were taking regimens used less often today and did not assess the impact of long-term side effects, adherence or drug resistance.
• Some studies show a higher risk of heart disease with continued use of certain NRTIs and PIs; higher rates of bone loss are linked to longer time on treatment.
• Some long-term side effects of newer HIV meds are not known and may not appear until 10 or more years of use.
• Possible side effects may decrease the quality of life for otherwise healthy people.
• Starting in this range increases the risk of earlier resistance, which may lead to running out of options.
• The current pipeline of experimental HIV meds is thin and may not produce many more drugs soon.
• Starting in this range may add 2–3 more years of total time on treatment.
• Starting in this range increases the risk of treatment fatigue, which could lead to poor adherence.
• May increase the collective cost of health care over time, and the current economy may make it difficult for some people to access public programs like ADAP to cover the cost of their meds and blood work.
• Results from START will not be available around 2014. (See section titled "The START study".)