Affordable third-line antiretrovirals are urgently needed in resource-limited settings, according to research conducted in Kenya and published in the online edition of AIDS. The study showed that a quarter of patients taking a failing second-line antiretroviral treatment regimen had exhausted current treatment options and only 18% had virus that was fully susceptible to the three main classes of anti-HIV drugs.
“This study in the Kenyan national ART [antiretroviral therapy] program suggests that about 27% of patients with second-line failure are in need of a switch to third-line therapy, with 25% demonstrating complete exhaustion of alternative first and second-line regimens,” comment the authors. “These data indicate an urgent need for increasing access to third-line drugs.”
An estimated 500,000 people in sub-Saharan Africa are taking second-line ART, which is typically based on a ritonavir-boosted protease inhibitor. Increaded access to routine viral load monitoring means this number is expected to increase to up to 6 million by 2030, approximately a fifth of all people taking ART.
Virological failure of second-line therapy has been reported in over a third of patients in sub-Saharan Africa. However, there are few data on the prevalence of drug resistance among these patients.
Investigators therefore designed a cross-sectional study involving individuals who accessed second-line treatment through the Kenyan national ART programme between 2010 and 2015 and who subsequently experienced the failure of this treatment.
Treatment failure was defined according to various criteria, including low CD4 cell count, emergence of HIV-related symptoms, and viral load rebound.
Blood samples from people with treatment failure were sent for resistance testing. The susceptibility of virus to first-, second- and third-line therapy was predicted.
Samples from 123 people were included in the analysis. These individuals had a median age of 24 years, median CD4 cell count was dangerously low at just 115 cells/mm3 and median viral load was 63,000 copies/ml. Patients had been taking ART for a median of six years and half this time was on second-line therapy. Almost all the patients (97%) were taking lopinavir-ritonavir and the most commonly used nucleoside reverse transciptase inhibitor (NRTI) backbones were tenofovir/lamivudine (35%) and abacavir/lamivudine (23%).
There was a very high prevalence of drug-resistant virus. Just under two-thirds (63%) of patients had at least one NRTI resistance mutation, mainly (51%) M184I/V, though resistance to older NRTIs such as zidovudine was also common (37%).
A third of patients had at least one protease inhibitor-associated resistance mutation. The median number of mutations was three.
A quarter of patients had resistance to the three main classes of antiretrovirals (NRTIs, NNRTIs and protease inhibitors). Only 34% of patients had virus with no resistance to NRTIs or protease inhibitors and just 18% had virus that was fully susceptible to all anti-HIV drugs.
Intermediate to high resistance to boosted protease inhibitors was common (lopinavir/ritonavir, 27%; atazanavir/ritonavir, 24%; darunavir/ritonavir, 7%).
Resistance to second generation NNRTIs was also highly prevalent (rilpivirine, 46%; etravirine, 36%).
A quarter of patients had completely exhausted all first- and second-line treatment options.
If anything, the investigators believe their study may have under-estimated the prevalence of second-line treatment failure, with many treatment centres lacking the tools to identify these patients.
Recommended third-line drugs are expensive, typically costing between 6 and 14 times more than first- and second-line therapies. Affording these drugs is a challenge for treatment programmes in low- and middle-income countries (LMICs), with Brazil currently spending at least 40% of its ART budget on the 5% of patients in need of third-line treatment.
“Our study indicates that nearly one in four patients in Kenya failing second-line treatment has complete exhaustion of available antiretrovirals, emphasizing the need for increased access to third-line treatment in LMICs,” conclude the authors.
Inzaule SC et al. Emergence of untreatable, multidrug-resistant HIV-1 in patients failing second-line therapy in Kenya. AIDS, online edition. DOI: 10.1097/QAD.0000000000001500 (2017).