An Overview of Human Immunodeficiency Virus-1 Antiretroviral Drugs: General Principles and Current Status

Treatment with highly active antiretroviral therapy (HAART) can prolong a patient's lifespan by disrupting pivotal steps in the replication cycle of the human immunodeficiency virus-1 (HIV-1). However, drug resistance is emerging as a major problem worldwide due to the prolonged period of treatment undergone by HIV-1 patients. Since the approval of zidovudine in 1987, over thirty antiretroviral drugs have been categorized into the following six distinct classes based on their biological function and resistance profiles: (1) nucleoside analog reverse-transcriptase inhibitors; (2) non–nucleoside reverse transcriptase inhibitors; (3) integrase strand transferase inhibitors; (4) protease inhibitors; (5) fusion inhibitors; and (6) co-receptor antagonists. Additionally, several antiretroviral drugs have been developed recently, such as a long active drug, humanized antibody and pro-drug metabolized into an active form in the patient's body. Although plenty of antiretroviral drugs are beneficially used to treat patients with HIV-1, the ongoing efforts to develop antiretroviral drugs have overcome the drug resistances, adverse effects, and limited adherence of drugs observed in previous drugs to some extent. Furthermore, studies focused on agents targeting latent HIV-1 reservoirs should be strengthened, as that may lead to eradication of HIV-1.

An Overview of Human Immunodeficiency Virus-1 Antiretroviral Drugs: General Principles and Current Status

Treatment with highly active antiretroviral therapy (HAART) can prolong a patient's lifespan by disrupting pivotal steps in the replication cycle of the human immunodeficiency virus-1 (HIV-1). However, drug resistance is emerging as a major problem worldwide due to the prolonged period of treatment undergone by HIV-1 patients. Since the approval of zidovudine in 1987, over thirty antiretroviral drugs have been categorized into the following six distinct classes based on their biological function and resistance profiles: (1) nucleoside analog reverse-transcriptase inhibitors; (2) non–nucleoside reverse transcriptase inhibitors; (3) integrase strand transferase inhibitors; (4) protease inhibitors; (5) fusion inhibitors; and (6) co-receptor antagonists. Additionally, several antiretroviral drugs have been developed recently, such as a long active drug, humanized antibody and pro-drug metabolized into an active form in the patient's body. Although plenty of antiretroviral drugs are beneficially used to treat patients with HIV-1, the ongoing efforts to develop antiretroviral drugs have overcome the drug resistances, adverse effects, and limited adherence of drugs observed in previous drugs to some extent. Furthermore, studies focused on agents targeting latent HIV-1 reservoirs should be strengthened, as that may lead to eradication of HIV-1.

The HIV-1 Virulence Factor Nef as a New Therapeutic Target Against HIV/AIDS

Human immunodeficiency virus-1 (HIV-1) encodes an accessory protein Nef.Initially, Nef had been known as a viral negative factor due to its no-effect on viral replication in the cancerous cell line system, however the pivotal role of Nef in disease progression has been discovered in primary culture and in vivo studies.The Nef protein is 27-35kDa, which is N-myristolated to attach on the intracellular membrane. Since it is already known that the nef-deleted virus is associated with long-term non-progression (LTNP), the roles of Nef linked to viral virulence were emphasized to develop an agent capable of inhibiting the progression of acquired immunodeficiency syndrome (AIDS). Nef plays multifaceted roles in host cell activities, which are recognized as the key functions of Nef-induced AIDS progression. Nef down-regulates the surface expression of several immune proteins including CD4, major histocompatibility complex class I (MHC-I/II), CD3. CD62L CXCR4, etc. Also, Nef disturbs the actin dynamics linked to vesicle trafficking and cell movement, and modulates the T-cell activation signaling associated with viral transcription. Here, we overview the molecular mechanisms of Nef with regard to AIDS pathogenesis and discuss various therapeutic approaches targeting Nef with a view to developing a new class of anti-AIDS agent capable of preventing the disease progression linked to Nef-induced CD4 down-regulation and HIV-1 replication.

The HIV-1 Virulence Factor Nef as a New Therapeutic Target Against HIV/AIDS

Human immunodeficiency virus-1 (HIV-1) encodes an accessory protein Nef.Initially, Nef had been known as a viral negative factor due to its no-effect on viral replication in the cancerous cell line system, however the pivotal role of Nef in disease progression has been discovered in primary culture and in vivo studies.The Nef protein is 27-35kDa, which is N-myristolated to attach on the intracellular membrane. Since it is already known that the nef-deleted virus is associated with long-term non-progression (LTNP), the roles of Nef linked to viral virulence were emphasized to develop an agent capable of inhibiting the progression of acquired immunodeficiency syndrome (AIDS). Nef plays multifaceted roles in host cell activities, which are recognized as the key functions of Nef-induced AIDS progression. Nef down-regulates the surface expression of several immune proteins including CD4, major histocompatibility complex class I (MHC-I/II), CD3. CD62L CXCR4, etc. Also, Nef disturbs the actin dynamics linked to vesicle trafficking and cell movement, and modulates the T-cell activation signaling associated with viral transcription. Here, we overview the molecular mechanisms of Nef with regard to AIDS pathogenesis and discuss various therapeutic approaches targeting Nef with a view to developing a new class of anti-AIDS agent capable of preventing the disease progression linked to Nef-induced CD4 down-regulation and HIV-1 replication.

Epidemiological characteristics of HIV infected Korean: Korea HIV/AIDS Cohort Study / 한국역학회지

OBJECTIVES: To manage evidence-based diseases, it is important to identify the characteristics of patients in each country.METHODS: The Korea HIV/AIDS Cohort Study seeks to identify the epidemiological characteristics of 1,442 Korean individuals with human immunodeficiency virus (HIV) infection (12% of Korean individuals with HIV infection in 2017) who visited 21 university hospitals nationwide. The descriptive statistics were presented using the Korea HIV/AIDS cohort data (2006-2016).RESULTS: Men accounted for 93.3% of the total number of respondents, and approximately 55.8% of respondents reported having an acute infection symptom. According to the transmission route, infection caused by sexual contact accounted for 94.4%, of which 60.4% were caused by sexual contact with the same sex or both males and females. Participants repeatedly answered the survey to decrease depression and anxiety scores. Of the total participants, 89.1% received antiretroviral therapy (ART). In the initial ART, 95.3% of patients were treated based on the recommendation. The median CD4 T-cell count at the time of diagnosis was 229.5 and improved to 331 after the initial ART. Of the patients, 16.6% and 9.4% had tuberculosis and syphilis, respectively, and 26.7% had pneumocystis pneumonia. In the medical history, sexually transmitted infectious diseases showed the highest prevalence, followed by endocrine diseases. The main reasons for termination were loss to follow-up (29.9%) and withdrawal of consent (18.7%).CONCLUSIONS: Early diagnosis and ART should be performed at an appropriate time to prevent the development of new infection.

Epidemiological characteristics of HIV infected Korean: Korea HIV/AIDS Cohort Study / 한국역학회지

OBJECTIVES@#To manage evidence-based diseases, it is important to identify the characteristics of patients in each country.@*METHODS@#The Korea HIV/AIDS Cohort Study seeks to identify the epidemiological characteristics of 1,442 Korean individuals with human immunodeficiency virus (HIV) infection (12% of Korean individuals with HIV infection in 2017) who visited 21 university hospitals nationwide. The descriptive statistics were presented using the Korea HIV/AIDS cohort data (2006-2016).@*RESULTS@#Men accounted for 93.3% of the total number of respondents, and approximately 55.8% of respondents reported having an acute infection symptom. According to the transmission route, infection caused by sexual contact accounted for 94.4%, of which 60.4% were caused by sexual contact with the same sex or both males and females. Participants repeatedly answered the survey to decrease depression and anxiety scores. Of the total participants, 89.1% received antiretroviral therapy (ART). In the initial ART, 95.3% of patients were treated based on the recommendation. The median CD4 T-cell count at the time of diagnosis was 229.5 and improved to 331 after the initial ART. Of the patients, 16.6% and 9.4% had tuberculosis and syphilis, respectively, and 26.7% had pneumocystis pneumonia. In the medical history, sexually transmitted infectious diseases showed the highest prevalence, followed by endocrine diseases. The main reasons for termination were loss to follow-up (29.9%) and withdrawal of consent (18.7%).@*CONCLUSIONS@#Early diagnosis and ART should be performed at an appropriate time to prevent the development of new infection.

PMA-induced up-regulation of MMP-9 is regulated by a PKCalpha-NF-kappaB cascade in human lung epithelial cells

Expression of matrix metalloproteinase-9 (MMP-9) is associated with airway remodeling and tissue injury in asthma. However, little is known about how MMP-9 is up-regulated in airway epithelial cells. In this study, we show that phorbol myristate acetate (PMA) induces MMP-9 expression via a protein kinase Calpha(PKCalpha)-dependent signaling cascade in BEAS-2B human lung epithelial cells. Pretreatment with either GF109203X, a general PKC inhibitor, or Go6976, a PKCalpha/beta isozyme inhibitor, inhibited PMA-induced activation of the MMP-9 promoter, as did transient transfection with PKCalpha antisense oligonuclotides. PMA activated NF-kappaB by phosphorylating IkappaB in these cells and this was also inhibited by GF109203X and Go6976, suggesting that PKCalpha acts as an upstream regulator of NF-kappaB in PMA-induced MMP-9 induction. Our results indicate that a "PKCalpha-NF-kappaB"-dependent cascade is involved in the signaling leading to PMA-induced MMP-9 expression in the lung epithelium.