Treatment of Acquired Immunodeficiency Syndrome After Failure of Darunavir- or Dolutegravir-Based Antiretroviral Therapy
This protocol applies to people with acquired immunodeficiency syndrome whose current antiretroviral regimen has not achieved adequate virologic suppression and for whom a next-line salvage approach is required.
Prior Treatment — Failure Condition
The preceding regimen — built around ritonavir-boosted darunavir combined with dolutegravir, or dolutegravir plus NRTIs (tenofovir alafenamide or tenofovir disoproxil fumarate with emtricitabine or lamivudine), or ritonavir-boosted darunavir plus NRTIs — did not achieve re-suppression of plasma HIV RNA to below 200 copies/mL within 4 to 8 weeks after the regimen change. Failure to reach this virologic goal is the trigger for escalation to this protocol.
Salvage Approach (partial)
When standard antiretroviral combinations are no longer sufficient, the salvage strategy centres on agents drawn from novel drug classes with mechanisms of action not shared by conventional antiretrovirals — including a CD4 post-attachment inhibitor — combined into a regimen of at least two fully active agents alongside an optimized background regimen.
Complete regimen composition, agent selection, and sequencing are in the full protocol below.
Clinical Goals
The primary aim is maximal virologic suppression of plasma HIV RNA to below 50 copies/mL where achievable. When full suppression cannot be attained, the goals shift to maintaining CD4 T lymphocyte count and achieving a meaningful reduction in plasma HIV RNA from baseline.
References
- If neither a fully active boosted PI nor a second-generation INSTI (e.g., DTG or BIC) is available, the new regimen should include at least two, and preferably three, fully active agents.
- People with HIV and ongoing detectable viremia who lack sufficient treatment options due to an inability to construct a fully suppressive regimen with common ARVs may be candidates for the first-in-class CD4 post-attachment inhibitor IBA, the gp120-directed attachment inhibitor FTR, and/or the capsid inhibitor LEN.
- At the end of 26 weeks (i.e., after one dose of SQ LEN), 81% of participants had RNA levels <50 copies/mL, and 89% had RNA levels <200 copies/mL, with a mean change in RNA level of −2.58 ± 1.04 log10 copies/mL.
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