Starting Treatment at Low Versus High CD4 Counts

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dnaLast month we blogged about the PBS lifting of the 500 CD4 cell count barrier to starting treatment, which is expected in April 2014. This month we review mounting evidence why it’s a good idea to start HIV treatment before the CD4 cell count falls to lower levels.

A large cohort study published in the Clinical Infectious Diseases (CID) Journal online in January of this year, and reported here www.aidsmeds.com/articles/low_CD4s_1667_25197.shtml, clearly demonstrated that CD4 cell immune recovery is difficult to obtain when starting treatment at or below 200 CD4 cells; despite long term (3 year) treatment suppressing viral load, and the risk of death was also significantly higher (12%) than those who could regain CD4 cells counts higher than 500 (2%) – more than double the risk of death.

Many factors were involved for those not able to achieve higher CD4 count recovery, in including older age, and how long it took to get the viral load down.  The outcomes, however, strongly suggest the importance of early treatment before the CD4 count falls to not only to 200, but also below 500, to provide the greatest survival from HIV-related and non-HIV-related death.

Other studies (Roger, A et al. AIDS 2013) have also shown matched mortality of HIV-positive people, living as long as HIV-negative people, when viral load is undetectable on treatment with a CD4 cell count above 500 (whether those CD4s are maintain or recovered). We think it’s better to maintain high CD4s than try to recover them, although this study authors cautioned against using their findings as evidence about the optimal time to start treatment.

Of course there are circumstances where treatment should be delayed, including the need to treat other co-infections or if the patient is not quite ready to start, but the Treatment Guidelines (www.arv.ashm.org.au) state to definitely start treatment before the CD4 count falls below 350.

Whilst the Treatment Guidelines contain the most robust evidence (randomised control trails) for this, you can nonetheless commence treatment at much higher counts even above 500 now. The benefits of this are evidenced in the aforementioned cohort studies, so as to:

  • preserve the immune system;
  • prevent death; and
  • stop the development of other conditions like cancer and liver disease.

There is also mounting evidence of the damage untreated HIV does the body systems. For instance, a French study also reported in the CID Journal (Lang S et al 2012) clearly demonstrated an independent risk of heart attack due to HIV replication and CD4 immune counts alone (over and above traditional risk factors for heart disease like smoking, high blood pressure and cumulative exposure to HIV treatment except for PIs which are known to raise blood fats).

Treatment also has the secondary benefit of reducing infectious to others by 96%.

But what is the highest CD4 level one could start treatment?

Thinking about CD4 T cell counts in people without HIV, 500 is the lower limit of a said “healthy immune system” in HIV-negative people, so should our goal for HIV health should be to never let the CD4 count fall to below this?

The upper CD4 limit in ‘’healthy individuals” without HIV is around 1100 or 1200, which indicates the highest level of health immunity – although we are certainly not suggesting people with HIV should start treatment at those high levels, as there is absolutely no evidence for that except that HIV infection is quite likely to quickly chomp away at your innate – before HIV infection – CD4 counts.  Those upper markers of high level immunity are unlikely to last anyhow in the presence of HIV. How fast they decline when HIV is present is another matter.

What other evidence is there for treating HIV at 500 CD4 cells?

A not so small recent Spanish cohort study (conducted by Lucero C et al, published in AIDS Res Hum Retroviruses Aug, 2013) among 574 people with HIV, who had current CD4 counts above 500 (median 630) for at least 1 year, noted that only those patients who never fell to less than 350 CD4 cells (at any time-point) had a highly significant (P<0.0001) reduced incidence of non-AIDS conditions (i.e. other serious diseases).

These researchers suggested that starting HIV treatment below this threshold doesn’t result in optimal immune recovery and thus doesn’t protect against these serious non-AIDS conditions.

The fact that these patients had high current CD4 count recovery on treatment above 500 (most of them around 630 CD4 cells) also suggest that early treatment at higher CD4 counts would prevent the risk in decay of CD4 counts falling below 350, thus avoiding the risk of disease.

Whilst this study doesn’t prove, nor clarify, at exactly what high level CD4 count treatment should be initiated, it seems to suggest a protective health benefit of starting treatment much earlier before CD4s to decline in the first place. It certainly suggests below350 is too late.

Until the results of the large randomised START study are known (which is currently examining whether to start above 500 CD4 cells or below), the true understanding of the clinical benefit of early treatment at greater than 500 CD4s remains limited.

Meantime, HIV-positive people are walking with their feet for earlier treatment it seems. A recent review in San Francisco (reported in J Infect Dis, Dec 2013), where treatment is offered to all HIV-patients regardless of CD4 count, the annual rate of starting treatment increased from 8% to 18% among people with a CD4 count greater than 500; and from 17% to 30% among people with counts of 351-500, but with no notable change for people with lower counts. Also the magnitude of the reduction in time to start after diagnosis was much greater among people with CD4 counts greater than 500 (from 37 months to 8 months) than those with counts of 351-500 (23 months to 5 months).

The bottom line is earlier treatment is better than delaying treatment, and the benefits of treatment far outweigh the risks (and burden) of daily treatment. If you are not happy with your CD4 counts you have the right to ask for treatment, and get it at any CD4 count (so long as there aren’t other medical reasons not to start). You also have a number of treatment choices to start with, so don’t forget that part and ask your doctor about these – it can be as simple as one pill once a day.