Abstract
Combined antiretroviral therapy (cART) is treatment with a combination of several antiretroviral drugs that block multiple stages in the virus replication cycle. An estimated 60% of the 38 million HIV-1 patients globally receive some form of cART. The benefits of cART for controlling HIV-1 replication, transmission, and infection rates have led to its universal recommendation. Implementation has caused a substantial reduction in morbidity and mortality of persons living with HIV-1/AIDS (PLWHA). More specifically, standard cART has provided controlled, undetectable levels of viremia, high treatment efficacy, reduction in pill burden, and an improved lifestyle in HIV-1 patients overall. However, HIV-1 patients living with AIDS (HPLA) generally show high viral loads upon cART interruption. Latently infected resting CD4+ T cells remain a major barrier to curing infected patients on long-term cART. There is a critical need for more effective compounds and therapies that not only potently reactivate latently infected cells, but also lead to the death of these reactivated cells. Efforts are ongoing to better control ongoing viral propagation, including the identification of appropriate animal models that best mimic HIV-1 pathogenesis, before proceeding with clinical trials. Limited toxicity profiles, improved drug penetration to certain tissues, and extended-release formulations are needed to cover gaps in existing HIV-1 treatment options. This review will cover past, current, and new cART strategies recently approved or in ongoing development.
Highlights
HIV-1 establishes a stably integrated, non-productive latent state of infection of individual cells, mainly long lived CD4+ T cells that are maintained by homeostatic proliferation [1,2]
Since HIV-1 has become a chronic illness managed with various combined antiretroviral therapy (cART) options, the number of patients over the age of 50 years keeps increasing with patients functioning and living successfully
Commitment to cART treatment is essential for long-term success
Summary
HIV-1 establishes a stably integrated, non-productive latent state of infection of individual cells, mainly long lived CD4+ T cells that are maintained by homeostatic proliferation [1,2]. This latent and stable reservoir is a primary barrier to HIV-1 eradication, despite the evident success of combined antiretroviral therapy (cART) [3]. The DHHS guidelines suggest cART with two nucleoside reverse transcriptase inhibitors (NRTIs) in combination with a third active drug for treatment-naive HIV positive individuals with completely susceptible virus [14]. The third active drug of choice consists of an integrase strand transfer inhibitor (INSTI)
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