High Rates of Virologic Failure Among Patients on Second-Line ART in Resource-Constrained Settings

Summary and Comment |
March 5, 2012

High Rates of Virologic Failure Among Patients on Second-Line ART in Resource-Constrained Settings

  1. Salim S. Abdool Karim, MD, PhD

Most of the failures are due to suboptimal adherence.

  1. Salim S. Abdool Karim, MD, PhD

A growing number of HIV-infected patients in resource-constrained settings are now on second-line antiretroviral therapy (ART), but little is known about outcomes in such patients. To that end, researchers conducted a systematic review of 19 studies involving 2035 patients on second-line ART in Botswana, South Africa, Malawi, Uganda, Tanzania, Cambodia, Thailand, and rural China.

The cumulative pooled proportion of patients with virologic failure on second-line ART was 22% at 6 months, 27% at 24 months, and 38% at 36 months. Mortality rates after 12 months of second-line therapy ranged from 5% to 11%.

Only five studies assessed the potential role of adherence in second-line treatment failure, but they were consistent in showing that patients with poor adherence had a significantly increased risk for failure. Drug resistance mutations were assessed in 78 patients with virologic failure and were found to be relatively uncommon: 20 patients (26%) had resistance to nucleoside reverse transcriptase inhibitors, 21 (27%) had resistance to nonnucleoside reverse transcriptase inhibitors, and 14 (18%) had resistance to protease inhibitors.

Comment

Despite some limitations of the data, including different definitions of failure among the studies and limited sample sizes, this systemic review shows that almost a quarter of patients have virologic failure within the first 12 months of second-line ART. Suboptimal adherence seems to be the main contributing factor, leading the authors to stress the importance of better adherence support, particularly for patients with virologic failure on first-line regimens. This study is a wake-up call because it suggests the potential for a scenario similar to what we've seen with tuberculosis — an inexorable progression toward widespread resistance to second- and third-line treatment.

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