Preventive and Therapeutic Features of Combination Therapy for HIV

The human immunodeficiency virus (HIV) is a retrovirus characterized by a reverse transcriptase enzyme and is known for causing acquired immune deficiency syndrome (AIDS), a chronic condition with progressive failure of the immune system. HIV poses a major health issue globally, infecting cells containing CD4+ and CCR5 or CXCR4 receptor sites, i.e., T-lymphocytes, macrophages, monocytes, and dendritic cells. HIV infects the T-lymphocytes by suppressing the immune system leading to several pathogenic infections, thus critically demands healthy measures to strengthen the immune system. For this purpose, diverse classes of drugs have been developed that effectively decrease the viral load in the patients, inhibiting the replicative cycle of HIV at a specific point. These specific inhibitors (drugs) may include inhibitors of entry/fusion, protease, nucleotide reverse transcriptase, non-nucleotide reverse transcriptase, and integrase. This chapter provides an overview of the drugs used to treat HIV, their mechanism of action and side effects, as well as their dosage recommended for the treatment of HIV. Notable examples are zidovudine, abacavir, lamivudine, didanosine, tenofovir, stavudine, emtricitabine, nevirapine, delavirdine, efavirenz, etravirine, dolutegravir, bictegravir, raltegravir, cobicistat, indinavir, ritonavir, nelfinavir, saquinavir, darunavir, atazanavir, lopinavir, tipranavir, fusion inhibitors (enfuvirtide) and chemokine CCR5 receptor antagonist. These drugs are administered to HIV patients throughout their life mostly as a combination therapy as HIV can become resistant to these drugs after some period. Additionally, these drugs have several side effects such as nausea, dizziness, liver diseases, kidney disorders, and heart diseases. Many of the above-mentioned side effects are temporary and are resolved spontaneously. However, some of these (hepatic, renal, or cardiac failure) can lead to the death of the patient. Another drawback of antiretroviral drugs is their latency for HIV and its reactivation. By determining and controlling all the factors that regulate the gene expression of HIV, such as HSP90, required for HIV gene expression, reactivation of HIV can be stopped from latency. Moreover, the latency of HIV can also be controlled by studying its mechanism, thus enhancing the effectiveness of antiretroviral treatment (ART). The development of plant-based drugs exhibiting improved inhibition of HIV replication compared to available antiretroviral drugs has also been reported.

Keywords: Antiretroviral drugs, Antiretroviral treatment, Cardiac failure, Human immunodeficiency virus, Macrophages, T-lymphocytes.