Changing ANTIRETROVIRAL Therapy due to Treatment Failure

HEALTH:

If a clinical assessment indicates the presence of treatment failure based on the set criteria, the best approach is to switch to a second-line regimen after ruling out non-adherence.

The new regimen should be comprised of at least two effective drugs to which the patients is naïve.

Before changing to the second-line drug regimen, the patient needs to go through the treatment readiness education process and adherence again.

This need to be carefully monitored, as some patients might hide their non-adherence.

Treatment failure can be virological, immunological and/or clinical.

It results from failure to suppress viral replication with the development of viral resistance.

The advantage of early diagnosis of treatment failure is that it is associated with less resistance-associated mutations (RAMS) and hence preserves future treatment options.

In contrast, late diagnosis of treatment failure using immunological (CD4) or clinical criteria is associated with accumulations of RAMS, which reduce future treatment options.

Transient rises in viral load are called viral blips and are not due to treatment failure.

A diagnosis of treatment failure requires two consecutive viral load levels after six months of treatment with HVL above 1000 copies/mL tested within an interval of three months after enhanced adherence counselling.

Second -Line ARV Regimen Options

Before treatment failure is presumed and a particular regimen discarded, every effort should be made to rule out causes other than drug resistance.

The factors listed below could result in sub-therapeutic drug levels and poor clinical response.

The patients should be evaluated for correctable factors, such as:

• Inappropriate dosing schedules
• Drug interactions that may reduce the efficacy of some of the ARV
• Non- adherence due to side effects
• Evidence of malabsorption

Each of the above scenarios could result in sub-therapeutic drug levels and poor clinical response.

In such cases, the regimen in question may be salvaged with palliative medication and/or patient education.

If a clinical assessment indicates the presence of treatment failure due to confirmed drug resistance, the best approach is to switch to an entirely new regimen, choosing two or more drugs to which the patients is naïve as the second-line drug regimen.

The review of WHO guidelines (2019) examined the efficacy and safety of Dolutegravir (DTG) combination with optimized Nucleoside Reverse Transcriptase Inhibitors (NRTI) backbone for people whom a non-DTG- based first-line regimen had failed.

The analysis showed that DTG is generally safer and more effective than the protease inhibitor (PI)-based second-line regimen.

Taking into consideration other advantages (i.e., lower cost, less potential drug-drug interactions, lower pill burden, and availability of once-daily fixed dose combinations), DTG is recommended as the preferred ARV drug for second-line ART among adults and adolescents for whom a non-DTG that has failed.

For those taking a first line regimen containing DTG that has failed, a boosted PI-containing regimen should be used.

Else, the second line NRTI choice for adults and adolescents depends on the first line. If patients were started on Tenofovir Disoproxil Fumarate(TDF) and had never used  Zidovudine(AZT) regimen, the default second-line option should be the Zidovudine(AZT)-based regimen:

Zidovudine (AZT)+Lamivudine(3TC) or Emtricitabine (FTC) combined with a ritonavir-boosted PI, either Ritonavir (LPV/r) or ATV/r. (TDF+3TC+ or FTC+LPV/r or ATV/r).

If patients were started on AZT and had never used TDF regimen, the default second-line option should be the TDF based regimen, i.e., TDF+3TC+ or FTC combined a ritonavir-boosted PI, either LPV/r or ATV/r.(TDF+3TC or FTC+LPV/r or ATV/r).

For a patients who were started on AZT in the first line because of intolerance to TDF, the default second line option is to use ABC plus 3TC combined with a ritonavir-boosted PI, either LPV/r or ATV/r.(ABC+3TC+LPV/r or ATV/r)

Drugs used as the second line dose in Zanzibar include:

• NRTIs: Zidovudine (AZT), Tenofovir (TDF), Abacavir (ABC), Lamivudine (3TC), and Emtricitabine (FTC)
• PIs: Atazanavir boosted by Ritonavir (ATV/r) or Lopinavir boosted by Ritonavir (LPV/r)
• INSTIs: Dolutegravir (DTG).