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Worrying rates of second-line HIV treatment failure

Healthworker dispenses medication at a clinic UNAIDS
Patients with HIV on second-line antiretroviral (ARV) treatment are significantly more likely to experience treatment failure than those on first-line treatment, according to new research by health NGO Médecins Sans Frontières (MSF).

Published in the Journal of the American Medical Association (JAMA), the MSF study looked at the treatment outcomes of 632 patients in resource-limited settings in Africa and Asia. The research found that patients who started second-line treatment at CD4 counts below 200, and who adhered to treatment less than 80 percent of the time, were more likely to experience treatment failure on second-line ARV regimens.

The research also showed that patients who had two of their nucleoside reverse transcriptase inhibitors (NRTIs) [a class of ARV medication] drugs changed at the start of second-line therapy were less likely to experience treatment failure than those who only had one of this kind of ARV changed.

''Understanding the difficulties faced by these patients is essential to help them to develop strategies allowing them to take their treatment correctly''
NRTIs interfere with the ability of the HI virus to replicate itself and are usually given in combination with other ARVs. Patients given combination, or "boosted" protease inhibitors - an ARV that blocks an enzyme crucial to replication - also experienced better treatment outcomes.

In total, nearly 20 percent of the patients who received second-line therapy for more than six months experienced treatment failure, and five percent died.

As ARV access improves in developing countries, an increasing number of patients will eventually need second-line drugs, which are used when patients stop responding to first-line regimens. According to the authors, preventing treatment failure in such patients is paramount because third-line drugs are either unaffordable or unavailable in many of these countries.

The drugs matter

The importance of specific ARVs in the treatment outcomes of second-line patients reaffirmed the need for a better and more varied ARV arsenal in developing countries, said lead author and MSF researcher Dr Mar Pujades-Rodriguez.

Although the World Health Organization (WHO) recommends incorporating boosted protease inhibitors into second-line regimens, almost half of the patients surveyed in the study were not on this type of drug, said Pujades-Rodriguez.

Second-line patients were 46 percent more likely to fail treatment than first-line patients, which the researchers attributed to the higher number of side effects associated with second-line drugs, and the greater likelihood of such patients experiencing drug resistance and treatment fatigue as a result of being on treatment longer.

Smaller health facilities, better care

The study also revealed that patients in rural areas, and those treated at primary health care facilities, were less likely to fail treatment than those treated at urban centres and hospitals.

More on second-line drugs
 Desperately seeking third-line medication
 ARV generics under threat from tighter patenting rules
 Straight talk with MSF medical coordinator Dr Eric Goemaere
"Health facilities in rural areas might be able to offer a more personalized approach and better psychological support to patients, enabling them to achieve and sustain better levels of adherence to therapy," Pujades-Rodriguez told IRIN/PlusNews.

"Urban sites are likely to treat many more patients, [who] frequently arrive with more severe diseases, and there might be less time available for the follow-up of stable patients."

Given the likelihood of treatment fatigue and negative experiences with first-line drugs, psycho-social support was particularly important to patients on second-line treatment, she said.

"These patients are likely to have experienced periods of sub-optimal adherence because of environmental, personal, or clinical reasons," she pointed out. "Understanding the difficulties faced by these patients is essential to help them to develop strategies allowing them to take their treatment correctly."

Recommendations in the study included improving the availability of second-line ARVs with fewer side-effects and in fixed-dose combinations [multiple ARVs combined in one pill] in developing countries.

The authors also called for better availability of diagnostic equipment to allow healthcare workers in resource-limited settings to diagnose treatment failure earlier, and at higher CD4 counts.

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This article was produced by IRIN News while it was part of the United Nations Office for the Coordination of Humanitarian Affairs. Please send queries on copyright or liability to the UN. For more information: https://shop.un.org/rights-permissions

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