Less Frequent CD4 and Viral Load Monitoring Safe for People Doing Well on ART

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The frequency of routine monitoring for people treated with antiretrovirals who have viral suppression can be safely reduced from every 3 months to every 6 months, investigators from Europe and the U.S. reported in the June 1 edition of the Journal of Acquired Immune Deficiency Syndromes. However, people followed-up every 9 to 12 months were more likely to experience virological failure and also had lower CD4 cell increases compared to people monitored every 3 months.

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"We found little evidence of an effect of monitoring frequency on death or AIDS-defining illness or death in the short term among individuals who achieve virologic suppression within 12 months of cART [combination antiretroviral therapy] initiation," commented the authors. "Our findings suggest that monitoring every 9-12 months increases the risk of virologic failure…this might reflect intermittent adherence among individuals monitored less frequently."

The benefits of immunological and virological monitoring for people with HIV is well known. However, there are few data to inform the frequency of follow-up for people doing well on HIV therapy.

Current European guidelines recommend frequent CD4 and viral load monitoring following the initiation of antiretrovirals, with check-ups every 3 to 6 months once viral load is suppressed to below 50 copies/mL and CD4 count has increased to over 500 cells/mm3.

In contrast, U.S. guidelines recommend viral load monitoring every 1 to 2 months after treatment initiation, with frequency reduced to every 3 to 4 months once viral load is undetectable, and after 2 years of viral suppression, the frequency of monitoring is further reduced to every 6 months. These guidelines also recommend CD4 count monitoring every 3 to 6 months in the period after starting treatment, with a decrease in frequency to every 12 months for people with an undetectable viral load and CD4 count above 300 cells/mmfor 2 years.

Given this uncertainty, investigators from the HIV-CAUSAL Collaboration used data from 6 large observational cohort studies in Europe and the U.S. to assess differences between 3 CD4 and viral load monitoring strategies.

Data were available for approximately 39,000 adults who started HIV therapy after the year 2000 and who achieved viral suppression within 12 months of treatment initiation.

People were monitored according to one of 3 strategies:

Two main outcomes were compared between these strategies:

During follow-up there were 265 deaths and 690 combined cases of AIDS-defining illness or death.

Compared with the 3-month monitoring strategy, the mortality hazard ratio (HR) was 0.86 for 6-month monitoring and 0.82 for monitoring every 9 to 12 months.

Estimated 18-month survival was 99% for monitoring every 3 months, 100% for monitoring every 6 months and 99% for monitoring every 9 to 12 months.

Corresponding 18-month AIDS-free survival was 99% for all monitoring strategies.

As regards virological failure, people monitored every 6 months were somewhat less likely to experience a sustained rebound in viral load to above 200 copies/mL (HR 0.74) compared to those with follow-up every 3 months. However, people monitored every 9 to 12 months were significantly more likely than those monitored every 3 months to experience virological failure (HR 2.35).

Using a viral load threshold of 50 copies/mL altered the results somewhat, but people with 9 to 12 month monitoring were still more likely to have virological failure compared to those with the most frequent follow-up, though the difference was no longer significant (HR 1.18).

The mean baseline CD4 count was 397 cells/mm3. After 18 months of treatment, this had increased to 506 cells/mm3 for people who had check-ups every 3 months, compared to 501 cells/mm3 for people followed-up every 6 months and 475 cells/mm3 for those monitored every 9 to 12 months.

"The mean CD4 count at 18 months was greater than 400 cells/mm3 for all of the monitoring strategies, and so the clinical relevance of these differences could be debated," suggest the investigators.

"Our findings suggest that less frequent monitoring of individuals on [combination] ART with confirmed virologic suppression has little effect on clinical outcomes by 18 months of follow-up," concluded the investigators. "Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question."

6/29/16

Reference

EC Caniglia, C Sabin, JM Robins, et al. When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study. Journal of Acquired Immune Deficiency Syndromes 72(2):214-221. June 1, 2016.