Initiating ART without CD4 testing increases early mortality risk

Issue: April 2019

SEATTLE — Patients who initiate ART without pretherapy CD4 monitoring experience a higher risk for early mortality than those who are tested, study data presented at CROI suggest.

Perspective from Kevin M. De Cock, MD, FRCP, DTM&H

Kombatende Sikombe , MPH , research manager at the Centers for Infectious Disease Research in Zambia, and colleagues noted that CD4 testing is no longer required in the “treat-all” era, and the practice is being phased out in some places. But CD4 testing “can play a crucial role in informing screening and prophylaxis for opportunistic infections, which are contributors to HIV-related mortality,” they wrote.

“We think that it’s important that patients are screened before initiating ART,” Sikombe said during a news conference. “Currently, the practice is to test and treat all. With this, we are missing some opportunistic infections in patients and we think that perhaps these patients are dying early.”

Using electronic medical records, Sikombe and colleagues assessed the association between presence of a pretherapy CD4 test and early mortality among 39,556 patients in Zambia who initiated ART between August 2013 and July 2015.

Among them, 76% had a record of a pretherapy CD4 test. According to the evaluation, the cumulative incidence of mortality after ART initiation was 5.12% (95% CI, 4.32-6.10). The cumulative incidence of mortality with pretherapy CD4 monitoring at 1 year was 4.54% (95% CI, 3.73-5.60) and it was 7.06% (95% CI, 5.14-9.98) without pretherapy CD4 monitoring.

After adjusting for pretherapy stage, sex, age, facility type and ART initiation date, Sikombe and colleagues found that patients without pretherapy CD4 monitoring had 1.48 times the hazard of mortality in the first year compared with tested patients (95% CI, 1.00-2.17).

“Even in the absence of CD4 monitoring and eligibility determination, there may still be an important role for use of CD4 for risk stratification and clinical management of immunocompromised patients,” Sikombe said. “As the investments in CD4 testing are drawn down, strategies to preserve limited clinical use should be investigated.” – by Caitlyn Stulpin

Reference:

Sikombe K, et al. Abstract 96. Presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2019; Seattle.

Disclosure: Sikombe reports no relevant financial disclosures.

Perspective

Kevin M. De Cock, MD, FRCP, DTM&H

There is a push by funders to reduce CD4 testing and scale up viral load testing because as we scale up access to ART, the most important test for monitoring is viral load. However, there is still this problem that some persons with HIV are presenting very late with advance disease with very low CD4 counts and they are at high risk for adverse outcomes and early mortality. If they do present to health care facilities, there are specific interventions required — they need to be screened for cryptococcal antigen or even cryptococcal disease; they are highly likely to have tuberculosis and may require special investigation for that; and they are a special category that needs more careful critical management and opportunistic infection prophylaxis. So, I think that monitoring these people, which you can only really do with CD4 counts, is potentially very, very important. This merits a broader discussion, and it is a discussion that needs to be had.

Kevin M. De Cock, MD, FRCP, DTM&H

Director, CDC’s country mission in Kenya

Disclosures: De Cock reports no relevant financial disclosures.

Conference on Retroviruses and Opportunistic Infections (CROI)

Initiating ART without CD4 testing increases early mortality risk

Perspective