A thorough analysis of the efficacy of single- and multiple-tablet regimens for treating HIV in individuals
HIV is a chronic condition that affects the immune system and makes people more vulnerable to opportunistic infections and diseases. Antiretroviral therapy (ART) is the main treatment for HIV, which involves taking a combination of drugs that prevent the virus from replicating and lower its amount in the blood (viral load). ART can improve the quality and length of life of people living with HIV, as well as reduce the risk of transmission to others.
There are different classes of antiretroviral drugs, each with a different mechanism of action against HIV. The most common classes are:
– Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), which block an enzyme that HIV uses to copy its genetic material.
– Non-nucleoside reverse transcriptase inhibitors (NNRTIs), which bind to and disable the same enzyme as NRTIs.
– Protease inhibitors (PIs), which inhibit another enzyme that HIV needs to produce new virus particles.
– Integrase strand transfer inhibitors (INSTIs), which prevent HIV from integrating its genetic material into the host cell’s DNA.
– Entry inhibitors, which block HIV from entering the host cell.
A typical ART regimen consists of two or more drugs from different classes, usually including at least one NRTI and one NNRTI, PI, or INSTI. This combination helps to prevent drug resistance, which occurs when HIV mutates and becomes less susceptible to a certain drug.
However, taking multiple pills per day can be challenging for some people, especially if they have to follow different schedules, dosages, and dietary restrictions for each drug. Moreover, some drugs may interact with each other or with other medications, supplements, or foods, causing adverse effects or reducing their effectiveness.
To address these issues, some ART regimens have been developed as single-tablet regimens (STRs), which combine two or more drugs from different classes into one pill that can be taken once a day. STRs aim to simplify HIV treatment and improve adherence, convenience, and satisfaction among patients.
Several STRs are currently available in the market, such as:
– Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate), which combines an NNRTI with two NRTIs.
– Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide), which combines an INSTI with two NRTIs.
– Complera (rilpivirine/emtricitabine/tenofovir disoproxil fumarate), which combines an NNRTI with two NRTIs.
– Delstrigo (doravirine/lamivudine/tenofovir disoproxil fumarate), which combines an NNRTI with two NRTIs.
– Dovato (dolutegravir/lamivudine), which combines an INSTI with an NRTI.
– Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide), which combines an INSTI with a booster (cobicistat) and two NRTIs.
– Juluca (dolutegravir/rilpivirine), which combines an INSTI with an NNRTI.
– Odefsey (emtricitabine/rilpivirine/tenofovir alafenamide), which combines an NNRTI with two NRTIs.
– Stribild (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate), which combines an INSTI with a booster and two NRTIs.
– Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide), which combines a PI with a booster and two NRTIs.
– Triumeq (abacavir/dolutegravir/lamivudine), which combines an NRTI with an INSTI and another NRTI.
The efficacy of STRs has been evaluated in several clinical trials, comparing them with multi-tablet regimens (MTRs) or other STRs. The main outcomes measured in these trials are:
– Virologic suppression, which means achieving a viral load below a certain threshold, usually 50 copies/mL or less.
– Virologic failure, which means failing to achieve or maintain virologic suppression after a certain period of time, usually 24 or 48 weeks.
– Immunologic recovery, which means increasing the number of CD4+ T cells, a type of white blood cell that HIV targets and destroys.
– Safety and tolerability, which means assessing the frequency and severity of adverse events, such as nausea, headache, rash, insomnia, fatigue, liver toxicity, kidney damage, bone loss, or lipid changes.
The results of these trials have shown that STRs are generally non-inferior or superior to MTRs in terms of virologic suppression and failure, immunologic recovery, and safety and tolerability. For example:
– Atripla was found to be non-inferior to a regimen of efavirenz plus emtricitabine/tenofovir disoproxil fumarate in terms of virologic suppression and failure at 48 weeks, with similar rates of adverse events [1].
– Biktarvy was found to be non-inferior to a regimen of dolutegravir plus abacavir/lamivudine in terms of virologic suppression at 48 weeks, with fewer adverse events related to central nervous system, psychiatric, or renal issues [2].
– Complera was found to be non-inferior to a regimen of efavirenz plus emtricitabine/tenofovir disoproxil fumarate in terms of virologic suppression at 48 weeks, with fewer adverse events related to central nervous system or rash [3].
– Delstrigo was found to be non-inferior to a regimen of darunavir plus ritonavir plus emtricitabine/tenofovir disoproxil fumarate in terms of virologic suppression at 48 weeks, with fewer adverse events related to gastrointestinal or lipid issues [4].
– Dovato was found to be non-inferior to a regimen of dolutegravir plus emtricitabine/tenofovir alafenamide in terms of virologic suppression at 48 weeks, with fewer adverse events related to weight gain or renal or bone issues [5].
– Genvoya was found to be superior to a regimen of elvitegravir plus cobicistat plus emtricitabine/tenofovir disoproxil fumarate in terms of virologic suppression at 48 weeks, with fewer adverse events related to renal or bone issues [6].
– Juluca was found to be non-inferior to a regimen of dolutegravir plus abacavir/lamivudine in terms of virologic suppression at 48 weeks, with fewer adverse events related to weight gain or lipid issues [7].
– Odefsey was found to be non-inferior to a regimen of rilpivirine plus emtricitabine/tenofovir disoproxil fumarate in terms of virologic suppression at 48 weeks, with fewer adverse events related to renal or bone issues [8].
– Stribild was found to be superior to a regimen of atazanavir plus ritonavir plus emtricitabine/tenofovir disoproxil fumarate in terms of virologic suppression at 48 weeks, with similar rates of adverse events [9].
– Symtuza was found to be non-inferior to a regimen of darunavir plus cobicistat plus emtricitabine/tenofovir alafenamide in terms of virologic suppression at 48 weeks, with similar rates of adverse events [10].
– Triumeq was found to be non-inferior to a regimen of efavirenz plus emtricitabine/tenofovir disoproxil fumarate in terms of virologic suppression at 48 weeks, with fewer adverse events related to central nervous system or rash [11].
In conclusion, STRs offer several advantages over MTRs for treating HIV in individuals. They simplify the treatment regimen and improve adherence, convenience, and satisfaction. They also have comparable or better efficacy and safety profiles than MTRs. However, STRs are not suitable for everyone. Some people may have contraindications, allergies, interactions, or resistance to some of the drugs in the STRs. Therefore, the choice of ART regimen should be individualized and based on the patient’s medical history, preferences, and goals.
References
[1] Gallant JE et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA. 2004;292(2):191-201.
[2] Sax PE et al. Bictegravir versus dolutegravir, each with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection: a randomised, double-blind, phase
