Less frequent CD4 and viral load monitoring safe for people doing well on ART

The frequency of routine monitoring for people treated with antiretrovirals with viral suppression can be safely reduced from every three months, to every six months, investigators from Europe and the United States report in the June 1st edition of the Journal of Acquired Immune Deficiency Syndromes. However, people followed-up every nine to twelve months were more likely to experience virologic failure and also had lower CD4 count increases compared to people monitored every three months.

“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”, comment 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 immunologic and virologic 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.


virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

AIDS defining condition

Any HIV-related illness included in the list of diagnostic criteria for AIDS, which in the presence of HIV infection result in an AIDS diagnosis. They include opportunistic infections and cancers that are life-threatening in a person with HIV.


Expresses the risk that, during one very short moment in time, a person will experience an event, given that they have not already done so.

hazard ratio

Comparing one group with another, expresses differences in the risk of something happening. A hazard ratio above 1 means the risk is higher in the group of interest; a hazard ratio below 1 means the risk is lower. Similar to ‘relative risk’.

observational study

A study design in which patients receive routine clinical care and researchers record the outcome. Observational studies can provide useful information but are considered less reliable than experimental studies such as randomised controlled trials. Some examples of observational studies are cohort studies and case-control studies.

Current European guidelines recommend frequent CD4 and viral load monitoring following the initiation of antiretrovirals, with check-ups every three to six months once viral load is suppressed to below 50 copies/ml and CD4 count has increased to over 500 cells/mm3. In contrast, US guidelines recommend viral load monitoring every one to two months after treatment initiation, with frequency reduced to every three to four months once viral load is undetectable and after two years of viral suppression, the frequency of monitoring is further reduced to every six months. These guidelines also recommend CD4 count monitoring every three to six 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/mm3 for two years.

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

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

People were monitored according to one of three strategies:

  • every three months
  • every six months
  • every nine to twelve months.

Two main outcomes were compared between these three strategies:

  • Clinical – all cause mortality and a combined end-point of AIDS or death within 24 months of follow-up.
  • Virologic failure (sustained increase in viral load above 200 copies/ml) and CD4 cell increase within 18 months of follow-up.

During follow-up, there were 265 deaths and 690 AIDS-defining illness or deaths.

Compared with the three-month monitoring strategy, the mortality hazard ratio (HR) was 0.86 (95% CI, 0.42-1.78) for six-month monitoring and 0.82 (0.46-1.47) for monitoring every nine to twelve months.

Estimated 18-month survival was 99% for monitoring every three months, 100% for monitoring every six months and 99% for monitoring every six to nine months.

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

As regards virologic failure, people monitored every six months were somewhat less likely to experience a sustained rebound in viral load to above 200 copies/ml (HR, 0.74; 95% CI, 0.46-1.19) compared to those with three-monthly follow-up. However, people monitored every nine to twelve months were significantly more likely than those monitored every three months to experience virologic failure (HR, 2.35; 95% CI, 1.56-3.54). Using a viral load threshold of 50 copies/ml altered the results somewhat, but people with nine-to-twelve month monitoring were still more likely to have virologic failure compared to those with the most frequent follow-up, though the difference was no longer significant (HR, 1.18, 0.88-1.59).

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 three months, compared to 501 for people followed-up every six months and 475 cells/mm3 for those monitored every nine to twelve 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 cART with confirmed virologic suppression has little effect on clinical outcomes by 18 months of follow-up,” conclude the investigators. “Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.”


Caniglia EC 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. J Acquir Immune Defic Syndr, 72: 214-21, 2016.