WHO-Mandated CD4 Monitoring for HIV Shows Poor Sensitivity, Specificity

Barbara Boughton

February 19, 2010

February 20, 2010 (San Francisco, California) — Viral load monitoring is significantly superior to CD4 monitoring in assessing viral suppression and treatment failure for HIV patients on antiretroviral therapy (ART) in resource-poor or developing countries, according to research presented here at the 17th Conference on Retroviruses and Opportunistic Infections (CROI).

The poor sensitivity, specificity, and positive predictive value of CD4 monitoring, commonly used in developing countries and recommended by the World Health Organization (WHO) as an alternative to viral load monitoring, could have serious consequences for HIV patients, study researchers said.

Reliance on CD4 monitoring instead of viral load monitoring can result in the increased cost of second-line therapies for those misdiagnosed as failures and increased risk for adverse events and development of resistance in those mistakenly identified as having suppressed the virus, said lead researcher Holly Rawizza, MD, from Brigham and Women's Hospital in Boston, Massachusetts.

Whether developing countries have the resources — especially in today's economic climate — to institute viral load monitoring for HIV patients remains an open question, according to other experts here at CROI.

In the largest study yet to assess WHO CD4 criteria to predict viral failure, Dr. Rawizza and colleagues analyzed the results of viral load and CD4 testing on 9690 HIV patients at 4 tertiary care centers in Nigeria, who receive healthcare from the Harvard PEPFAR program. The program has provided healthcare to more than 68,000 HIV patients since 2004.

Patients underwent CD4 and viral load testing at baseline, 3 and 6 months after ART initiation, and every 6 months thereafter. Patients were followed for a median of 3 years, and failure was defined as 2 consecutive viral loads of 1000 cpm or more after 6 months on ART.

Results showed that 1355 patients experienced failure according to both immunologic and virologic criteria, as did 1158 according to virologic criteria only and 1712 according to immunological criteria only. The sensitivity of CD4 criteria to detect viral load failure was 53.9%, the specificity was 76.1%, and the positive predictive value was 44.2%.

"The sensitivity of CD4 testing suggests that nearly half of patients with failure would be missed using CD4 monitoring alone," Dr. Rawizza said. These missed diagnoses could result in the accumulation of resistance mutations, since patients would be mistakenly maintained on nonsuppressive regimens, she added. In her study, viral load measurement also detected failure significantly earlier — 4 months earlier than CD4 criteria. That's significant because delayed diagnoses could result in increased risk for drug resistance, Dr. Rawizza said.

Because CD4 criteria identifies a greater number of failures than virologic criteria, and is more likely to identify patients who have actually suppressed the virus as treatment failures, the result would be expensive program-wide switches to second-line therapies that could increase medication costs by 25%, Dr. Rawizza said.

The cost of viral load testing in Nigeria is $20 per test, but the PEPFAR program would have the resources to scale up viral load monitoring in developing countries, she noted. She conceded, however, that in some settings the cost of viral load testing would be prohibitive. "That's why funding should be used to develop less expensive viral load quantification techniques, and innovation in HIV RNA quantification methods should be encouraged," she said.

While acknowledging the technical superiority of viral load over CD4 monitoring, experts at the CROI meeting questioned whether viral load testing is really practical today in developing countries. "The technological challenges can be overcome in resource-poor countries. The problem is that we don't have the resources to take care of the dramatically increased numbers of HIV patients in Africa, and patients are not even getting basic first-line therapies," said Peter Mugyenyi, MD, director of the Joint Clinical Research Center in Kampala, Uganda.

"If we had a good, widely available viral load test, it would replace the need for CD4 monitoring," he added. "The problem is one of resources. Many successful programs in Africa are being threatened, so that patients can't even access therapies, resulting in the real problem of emerging resistance," he said.

Dr. Rawizza and Dr. Mugyenyi have disclosed no relevant financial relationships.

17th Conference on Retroviruses and Opportunistic Infections (CROI): Abstract 111. Presented February 18, 2010.

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