Antiretroviral therapy “à la carte”
Vicente Soriano
UNIR Health Sciences School and Medical Center, Madrid, Spain
*Correspondence: Vicente Soriano. Email: vicente.soriano@unir.net
Contents
The World Health Organization (WHO) estimates that more than 41 million people are currently living with HIV infection worldwide. Every year, about 1.3 million new infections occur (UNAIDS 2025). Antiretroviral treatment has improved dramatically over the past 30 years, so that there are hardly any cases of AIDS in people with access to the medication.
Antiretroviral therapy is able to almost completely suppress viral replication and prevent the progression of immunodeficiency in most persons infected with HIV. However, these medications do not eliminate the viral infection, so if treatment is discontinued, HIV reactivates, and the risk of AIDS reappears. Thus, adequate adherence to treatment, without forgetting to take it, is important to avoid selection of resistance to antiretroviral drugs and disease progression.
Three new therapeutic options
To provide alternatives to available antiretroviral treatment modalities, new medication regimens have been investigated. Results have recently been published for three new combinations that allow daily, weekly, or monthly administration (Table 1).
Table 1. The newest options for antiretroviral therapy
| Combination | Dosing | Study | Reference |
|---|---|---|---|
| Bictegravir + lenacapavir | STR, oral Once daily | ANTISTRY1 trial | Orkin et al. Lancet 2026 |
| Islatravir + lenacapavir | Two pills, oral Once weekly | Phase II | Colson et al. Ann Intern Med 2026 |
| Cabotegravir + rilpivirine | Intramuscular Once monthly | LATITUDE trial | Rana et al. N Engl J Med 2026 |
|
STR: single tablet regimen. |
|||
Bictegravir + lenacapavir
It is an oral combination of a second-generation integrase inhibitor and an HIV capsid inhibitor, co-formulated in a single pill, which is administered in a single daily dose. Both drugs are from Gilead. The ARTISTRY-1 study has demonstrated the non-inferiority of this experimental regimen compared with a standard-of-care treatment (Orkin et al., Lancet 2026).
Islatravir + lenacapavir
Islatravir (Merck) is a new polymerase inhibitor, highly potent and the first in its class (de Mendoza and Soriano, Lancet HIV 2020). In a phase II clinical trial, this regimen of two weekly pills has demonstrated non-inferiority compared with a standard daily triple treatment (Colson et al., Ann Intern Med 2026).
Cabotegravir + rilpivirine
Both drugs have been developed as long-acting antiviral (XLA) formulations that are administered once a month as an intramuscular injection into the buttocks. Cabotegravir (Viiv) is an integrase inhibitor, and rilpivirine (Janssen) is an allosteric polymerase inhibitor. In the LATITUDE trial, results with this regimen were superior to those with daily oral medication in patients with treatment adherence problems (Rana et al., N Engl J Med 2026).
Challenges for Sub-Saharan Africa
While these innovations will further help curb the HIV/AIDS pandemic in developed countries, antiretroviral treatment availability continues to experience increased challenges in underdeveloped regions.
In 2003, President George W. Bush created PEPFAR, the greatest national effort against a single disease. In two decades, PEPFAR has provided free antiretroviral treatment to 20 million people, saved over 25 million lives, helped 7 million babies be born HIV-free, and halved new HIV infections (Abdool Karim et al., N Engl J Med 2023). I have personally witnessed PEPFAR’s beneficial impact in the Ivory Coast (Konan et al., AIDS Rev 2024).
In early 2025, the U.S. administration drastically cut funding for PEPFAR, compromising the distribution of antiretrovirals in many Third World countries. UNAIDS modeling has warned that, without funding, there could be a significant rebound in the number of people infected with HIV and mortality from AIDS, with an increase of more than 6 million infected and more than 4 million deaths by 2029 (Montaner et al., Sex Transm Infect 2026). It is time for international organizations (UN, WHO, G7) to take the initiative and maintain a solidarity program that has been one of the most successful in the history of global public health.
