Recycling tenofovir better than zidovudine switch for HIV

Recycling tenofovir after failure of first-line treatment vs switching to second-line zidovudine is associated with better care retention, adherence, and viral load suppression in HIV patients, especially when combined with atazanavir boosted with ritonavir, a new study presented at AIDS 2020 Virtual has shown.

WHO guidelines recommend an optimized NRTI* backbone for second‐line antiretroviral treatment (ART), including switching from tenofovir to zidovudine, if first-line treatment fails.

However, the side effects of zidovudine, including nausea, anaemia, and limb fat loss, make it an unattractive option for second-line treatment. The twice-daily dosing of zidovudine also  poses adherence issues to some patients.

“Treatment toxicity and pill burden should be taken into consideration when selecting a treatment regimen after first-line failure,” said study investigator Dr Samuel Pierre from the GHESKIO Centres, Research in Port‐au‐Prince, Haiti.

An alternative second-line option is to recycle tenofovir as part of a new combination, based on limited evidence that recycling the drug contributes to viral suppression despite the presence of the K65R mutation.

Tenofovir recycling: What’s the evidence?

ART adherence is crucial for long-term HIV treatment success. There is good evidence that recycling tenofovir in the second-line setting may contribute to viral suppression, said Pierre.

In the current retrospective review, the researchers sought to determine if continued use of tenofovir in second-line treatment would work well for adult HIV patients in Haiti vs switching to zidovudine. Patients were on first-line regimen of tenofovir, lamivudine, and efavirenz and were switched to a second-line regimen that included ritonavir-boosted protease inhibitor (bPI), in combination with either tenofovir/lamivudine (TDF/3TC) or zidovudine/lamivudine (AZT/3TC). Adherence based on pharmacy refill data and viral suppression below 200 copies/mL within 12 months of switching were assessed. [AIDS 2020 Virtual, abstract OAB0405]

Of 1,017 patients (509 women, median age 40.7 years), 284 were switched to AZT/3TC and 733 continued with TDF/3TC. Retention in care did not differ between switchers and non-switchers (83 percent for each group).

Lower viral load, better adherence with tenofovir

Viral suppression in patients with ≥90 percent adherence was better in the TDF/3TC group than in the AZT/3TC group (p<0.016). Non-switchers were significantly more likely to have a viral load below 200 copies/mL on their first viral load test after 12 months, with more than half of them having an undetectable viral load during that period (p<0.001).

Predictors of viral suppression included recycled TDF/3TC (odds ratio [OR], secondary or higher education level (OR, 1.53), and being married/living together (OR, 1.51).

In terms of adherence, non-switchers had significantly better adherence – 48 percent had adherence of ≥90 percent vs 38 percent for switchers (p=0.006).

Further analysis of outcomes according to the second-line bPI showed that non-switchers on atazanavir were significantly more likely than switchers to be retained in care after 12 months, to have 12-month adherence >90 percent, and to have a first viral load test below 200 copies/mL.