Improving combination antiretroviral therapy by targeting HIV-1 gene transcription.
Combination Antiretroviral Therapy (cART) has not allowed the cure of HIV. The main obstacle to HIV eradication is the existence of quiescent reservoirs. Several other limitations of cART have been described, such as strict life-long treatment and high costs, restricting it to Western countries, as well as the development of multidrug resistance. Given these limitations and the impetus to find a cure, the development of new treatments is necessary. Areas covered: In this review, we discuss the current status of several efficient molecules able to suppress HIV gene transcription, including NF-kB and Tat inhibitors. We also assess the potential of new proteins belonging to the intriguing DING family, which have been reported to have potential anti-HIV-1 activity by inhibiting HIV gene transcription. Expert opinion: Targeting HIV-1 gene transcription is an alternative approach, which could overcome cART-related issues, such as the emergence of multidrug resistance. Improving cART will rely on the identification and characterization of new actors inhibiting HIV-1 transcription. Combining such efforts with the use of new technologies, the development of new models for preclinical studies, and improvement in drug delivery will considerably reduce drug toxicity and thus increase patient adherence.
a Institut de Parasitologie et de Pathologie Tropicale, EA7292 , Université de Strasbourg , Strasbourg , France.|b IUT de Schiltigheim , Schiltigheim , France.|c UCD Centre for Research in Infectious Diseases (CRID) School of Medicine and Medical Science , University College Dublin , Dublin 4 , Ireland.
Valentin
V
Le Douce
a Institut de Parasitologie et de Pathologie Tropicale, EA7292 , Université de Strasbourg , Strasbourg , France.
Amina
A
Ait-Amar
a Institut de Parasitologie et de Pathologie Tropicale, EA7292 , Université de Strasbourg , Strasbourg , France.
Faezeh
F
Forouzan Far
a Institut de Parasitologie et de Pathologie Tropicale, EA7292 , Université de Strasbourg , Strasbourg , France.
Faiza
F
Fahmi
a Institut de Parasitologie et de Pathologie Tropicale, EA7292 , Université de Strasbourg , Strasbourg , France.
Jose
J
Quiel
a Institut de Parasitologie et de Pathologie Tropicale, EA7292 , Université de Strasbourg , Strasbourg , France.
Hala
H
El Mekdad
a Institut de Parasitologie et de Pathologie Tropicale, EA7292 , Université de Strasbourg , Strasbourg , France.
Fadoua
F
Daouad
d Faculté de Chirurgie Dentaire , Inserm UMR 1121 , Strasbourg , France.
Céline
C
Marban
a Institut de Parasitologie et de Pathologie Tropicale, EA7292 , Université de Strasbourg , Strasbourg , France.|b IUT de Schiltigheim , Schiltigheim , France.|e Institut Universitaire de France , Paris , France.
Olivier
O
Rohr
a Institut de Parasitologie et de Pathologie Tropicale, EA7292 , Université de Strasbourg , Strasbourg , France.|b IUT de Schiltigheim , Schiltigheim , France.
Christian
C
Schwartz
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D016503:Drug Delivery Systems; D015195:Drug Design; D024921:Drug Resistance, Multiple, Viral; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000178:diet therapy / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D055118:Medication Adherence; D014158:Transcription, Genetic / Q000187:drug effects
D019380:Anti-HIV Agents
DING; HIV transcription; NF-KB; Tat; cART