How do we treat Acquired Immune Deficiency Syndrome (AIDS) with multiple drug-resistant genes?

From the Guidelines

Treatment of AIDS with multiple drug-resistant HIV should involve using a combination of antiretroviral medications selected through resistance testing, prioritizing newer agents from different drug classes to which the virus has not developed resistance, such as dolutegravir or bictegravir, along with effective NRTIs and potentially additional medications like ibalizumab or fostemsavir for highly resistant cases. When managing virological failure, especially in patients with a complex treatment history, the goal is to use at least 2 fully active drugs from different antiretroviral drug classes 1. For individuals with multidrug resistance, optimization of the antiretroviral therapy (ART) regimen to keep the HIV viral load as low as possible is desirable, and adding a single active drug to the failing regimen is not recommended 1. Key considerations in the treatment approach include:

• Using integrase strand transfer inhibitors (INSTIs) like dolutegravir (50mg daily) or bictegravir (part of Biktarvy) as part of the regimen 1.
• Combining INSTIs with two nucleoside reverse transcriptase inhibitors (NRTIs) that testing shows effectiveness against 1.
• For highly resistant cases, considering the addition of medications from newer classes like ibalizumab (a CD4-directed post-attachment HIV-1 inhibitor) or fostemsavir (an attachment inhibitor) 1.
• Ensuring treatment is lifelong and adherence is crucial to prevent further resistance development.
• Regular viral load monitoring (every 3-6 months) to assess treatment effectiveness 1. In the context of real-life clinical medicine, the focus should be on maximizing the use of effective, newer antiretroviral agents, given their superior efficacy and safety profiles compared to older medications, as evidenced by recent guidelines and studies 1.

From the FDA Drug Label

TMC114-C229 is a randomized, open-label trial comparing darunavir/ritonavir 800 mg/100 mg once daily to darunavir/ritonavir 600 mg/100 mg twice daily in treatment-experienced HIV-1-infected patients with screening genotype resistance test showing no darunavir resistance associated substitutions (i. e. V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V) and a screening viral load of greater than 1,000 HIV-1 RNA copies/mL. The median increase from baseline in CD4+ cell counts was comparable for both treatment arms (108 cells/mm3 and 112 cells/mm3 in the darunavir/ritonavir 800 mg/100 mg once daily arm and the darunavir/ritonavir 600 mg/100 mg twice daily arm, respectively)

The treatment for AIDS with multiple resistant genes involves the use of darunavir/ritonavir in combination with an optimized background regimen. The dosage of darunavir/ritonavir can be either 800 mg/100 mg once daily or 600 mg/100 mg twice daily. The choice of dosage may depend on the individual patient's needs and the specific resistance profile of the virus.

• Key points:
  • Darunavir/ritonavir is effective in treatment-experienced patients with no darunavir resistance associated substitutions.
  • The median increase in CD4+ cell counts is comparable between the two dosage regimens.
  • The optimized background regimen should be selected based on the patient's resistance profile and treatment history. 2

From the Research

Treatment of AIDS with Multiple Resistant Genes

• The treatment of AIDS with multiple resistant genes is a complex issue, and researchers have been working to develop effective combination antiretroviral therapies (cART) to address this challenge 3, 4, 5.
• cART involves the use of multiple antiretroviral drugs that block different stages of the virus replication cycle, and it has been shown to be effective in controlling HIV-1 replication, transmission, and infection rates 3.
• However, the development of resistance to antiretroviral drugs is a major concern, and researchers are working to identify new compounds and therapies that can effectively reactivate latently infected cells and lead to their death 3.

Combination Antiretroviral Therapy (cART) Options

• Several cART options are available, including the use of nucleoside analog reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors 4.
• The choice of cART regimen depends on various factors, including the patient's prior history of antiretroviral use, side effects, and drug-drug interactions 4.
• Recent studies have shown that two-drug regimens, such as the combination of lamivudine and a boosted protease inhibitor or integrase inhibitor, may be effective in treating HIV-infected naive patients 6.

New Developments in cART

• New antiretroviral drugs, such as bictegravir, have been developed and shown to be effective in treating HIV-1 infection 7.
• Bictegravir is a novel, once-daily, unboosted integrase strand transfer inhibitor that has a high in-vitro resistance barrier and has been shown to be well-tolerated and effective in clinical trials 7.
• The development of new cART strategies, including the use of two-drug regimens, may provide new options for the treatment of AIDS with multiple resistant genes 6.