Switch Strategies

Switch Strategies for Virologically Suppressed Persons

Definition of Virologically Suppressed

Clinical trials exploring switching strategies have generally defined suppression as an HIV-VL < 50 copies/mL for at least 6 months

Indications

  1. Documented toxicity caused by one or more of the antiretrovirals included in the regimen, see Adverse Effects of ARVs and Drug Classes
  2. Prevention of long-term toxicity, see Adverse Effects of ARVs and Drug Classes. This may include person's concerns about safety
  3. Avoidance of drug-drug interactions, see DDIs, this includes ART switch when starting HCV treatment to avoid DDIs, see Drug-drug Interactions between DAAs and ARVs
  4. Planned pregnancy or women wishing to conceive, see Treatment of Pregnant Women Living with HIV or Women Considering Pregnancy
  5. Ageing and/or co-morbidity with a possible negative impact of drug(s) in current regimen, e.g. on CVD risk, metabolic parameters
  6. Simplification: to reduce pill burden, adjust food restrictions, improve adherence and reduce monitoring needs
  7. Protection from HBV infection or reactivation by including tenofovir in the regimen
  8. Regimen fortification: Increasing the barrier to resistance of a regimen in order to prevent VF (e.g. in persons with reduced adherence)
  9. Cost reduction: switching to the generic form of their current regimen, if available

Principles

Clinicians should always review possible adverse events or tolerability issues with current antiretroviral regimens. Just because the viremia is suppressed it should not be assumed that the PLWH is well adapted and tolerating the current regimen

  1. The objectives of treatment modification should be to eliminate or improve adverse events, facilitate adequate treatment of comorbid conditions, and improve quality of life. The primary concern when switching should be to sustain and not to jeopardize virological suppression. In persons without prior virological failures and no archived resistance, switching regimens entail a low risk of subsequent failure if clinicians select one of the recommended combinations for first-line therapy. The majority of clinical trials showing non-inferiority of the new regimen after the switch have actively excluded persons with prior virological failures and historical resistance
  2. The complete ARV history with HIV-VL, tolerability issue, cumulative genotypic resistance history and/or phases of viremia on previous regimens with the potential of resistance development should be evaluated prior to any drug switch
  3. Switches within the same drug class (i.e. TDF/FTC -> TAF/FTC, EFV -> DOR or RPV) are usually virologically safe if  equal potency and in the absence of resistance
  4. Cross-class switches of single drugs with the same genetic resistance barrier (for example EFV to RAL) are usually virologically safe in the absence of resistance to the new compound
  5. In case of prior virologic failures, with or without evidence of resistance, switches have to be planned especially carefully when they result in a lower barrier to resistance of the regimen. A PI/b may only be switched to unboosted ATV, an NNRTI, INSTIs RAL and EVG if full activity of the 2 NRTIs in the new regimen can be assumed based on resistance data, ARV history and HIV-VL results before switching (see 2.) Due to the higher barrier to resistance of DTG and BIC, it is currently unclear if a switch to DTG- or BIC-based regimens also requires full activity of 2 NRTIs in the combination
  6. Before switching, remaining treatment options in case of potential virological failure of the new regimen should be taken into consideration. This requires knowledge about the resistance selection profile of the switch regimen. Especially, when reducing the number of drugs in a regimen or its barrier to resistance, the chances of composing a fully suppressive regimen after potential failure following switch should be considered
  7. Proviral DNA genotyping may be useful in persons with multiple virological failures, unavailable resistance history or low-level viremia at the time of switch. Results ought to be taken cautiously as proviral DNA genotype may not detect previous resistance mutations and can also detect clinically irrelevant mutations.  Therefore, routine proviral DNA genotyping is currently not recommended
  8. When selecting a new regimen, clinicians should carefully review the possibility of new drug-drug interactions with antiretroviral and concomitant medication leading to suboptimal drug exposure or toxicity, as well as the lag time for hepatic enzyme induction or blockade following discontinuation of the offending drug. Examples are: increased TDF toxicity with a PI/b or an increase in metformin exposure with DTG
  9. If the switch implies discontinuing TDF and not starting TAF, clinicians should check the HBV and HBV vaccination status. TDF or TAF should not be discontinued in persons with chronic HBV
  10. PLWH should be seen soon (e.g. 4 weeks) after treatment switches to check for maintenance of suppression and possible toxicity or tolerability issues of the new regimen
  11. If a PLWH receives and tolerates a regimen that is no longer a preferred option, and none of the other reasons for change applies, there is no need to change. Example: persons tolerating EFV-containing regimens
  12. See online video lecture How to Change ART from the EACS online course Clinical Management of HIV

Dual therapies

In persons with suppression of HIV-VL < 50 copies/mL for the past 6 months these dual therapy strategies should only be given if there is
a) no historical resistance and
b) HBV immunity or if non-immune concomitant HBV Vaccination

Dual therapies supported by large randomized clinical trials or meta-analyses:

  • DTG + RPV
  • XTC + DTG
  • XTC + DRV/b
  • Long-acting CAB + RPV bi-monthly injections

In clinical trials, these strategies have not been associated with more virological rebounds than triple therapy. There were a few cases of resistance development on DTG + RPV and CAB + RPV

Dual therapy options supported only by small trials:

These regimens should be indicated only in persons not eligible for other treatment combinations due to intolerance or resistance to other drugs

  • DRV/b + RPV
  • DRV/b + DTG

Strategies not recommended

  1. Monotherapy with a PI/b
  2. Monotherapy with DTG
  3. Dual or triple NRTIs combinations
  4. Specific two-drug combination, i.e.1 NRTI + 1 NNRTI or 1 NRTI + 1 unboosted PI, 1 NRTI + RAL, MVC + RAL, PI/b + MVC, ATV/b + RAL
  5. Intermittent therapy, sequential or prolonged treatment interruptions. In a randomized study, 4 consecutive days a week of triple therapy with DRV/b or DTG was as effective as 7 days a week, at 48 weeks in the context of close monitoring and counseling with visits every 3 months