High treatment failure rate among Thai children switching to second-line ART

There is a high treatment failure rate among children taking second-line antiretroviral therapy (ART), Thai investigators report in the online edition of Clinical Infectious Diseases. Therapy was based on a protease inhibitor (PI) and 50% experienced virological failure within five years of switching to second-line treatment.

“Treatment failure was independently associated with longer exposure to first-line ART, older age and thinness at second-line initiation as well as undetectable drug levels after second-line investigation,” note the investigators, who suggest these issues should now be addressed.

Approximately a third of children with HIV living in low- and middle-income settings have experienced treatment failure within twelve months of starting first-line ART based on an NNRTI (non-nucleoside reverse transcriptase inhibitor). Recommended second-line therapy is based on a protease inhibitor, and the number of children taking such therapy in poorer countries appears to be increasing.

Glossary

second-line treatment

The second preferred therapy for a particular condition, used after first-line treatment fails or if a person cannot tolerate first-line drugs.

treatment failure

Inability of a medical therapy to achieve the desired results. 

first-line therapy

The regimen used when starting treatment for the first time.

middle income countries

The World Bank classifies countries according to their income: low, lower-middle, upper-middle and high. There are around 50 lower-middle income countries (mostly in Africa and Asia) and around 60 upper-middle income countries (in Africa, Eastern Europe, Asia, Latin America and the Caribbean).

protease inhibitor (PI)

Family of antiretrovirals which target the protease enzyme. Includes amprenavir, indinavir, lopinavir, ritonavir, saquinavir, nelfinavir, and atazanavir.

Many of these children have no access to third-line regimens in the event of second-line treatment failure. It is therefore important to ensure that second-line combinations are as durable as possible. However, relatively little is known about the proportion of children whose viral load rebounds after switching to second-line treatment or the risk factors for this outcome.

To clarify these questions, Thai investigators designed an observational cohort study involving 111 children (aged under 18 years) who started protease inhibitor-based second-line treatment between 2002 and 2010. Virological failure was defined as a confirmed viral load above 400 copies/ml, six months after switching treatment.

Most (53%) were girls and the median duration of first-line ART was 1.9 years. Almost all the participants changed therapy because of virological failure, and at the time therapy was switched, 96% had resistance to at least one NRTI or NNRTI.

At treatment switch, the study participants had a median age of 11 years. Average viral load was approximately 16,000 copies/ml and median CD4 cell count was 372 cells/mm3.

Within six months of starting second-line treatment, 27% of children were considered non-adherent using plasma drug-level monitoring and 14% by adherence self-report.

The median duration of follow-up was 4.4 years. Overall, half the children experienced treatment failure: 54 cases of sustained viral rebound and two deaths.

Over a third (35%) had experienced failure after twelve months, increasing to 41% at month 24 and 54% at month 60.

Factors independently associated with failure of therapy were longer duration of first-line ART (p = 0.03), age 13 years and older (p < 0.001), low body mass for age (p = 0.03) and undetectable drug levels within six months of treatment change (p < 0.001).

Drug resistance was present in 70% of those experiencing treatment failure, including six individuals with resistance to protease inhibitors.

“Our study shows a high rate of treatment failure in HIV-infected children on PI-containing second-line ART,” conclude the authors. “Novel interventions to improve outcomes could include simple, non-invasive point-of-care testing of antiretroviral drug concentrations to regularly assess drug adherence, peer group counseling, use of long-acting injectable drugs in adolescents, and addressing nutritional issues in this population.”

References

Suaysod R et al. Treatment failure in HIV-infected children on second-line protease inhibitor-based antiretroviral therapy. Clin Infect Dis, online edition, 2015.