Antiretroviral Therapy for HIV-Infected Adults Disease Background

Introduction

Epidemiology

Globally, as of 2021, reported cases to the World Health Organization (WHO) were approximately 28.4 million (33.9-43.8 million), with an estimated 3.8 million people coming from South-East Asia. There have been 40.1 million deaths reported to the WHO globally as of 2021, with 650,000 (510,000-860,000) deaths due to HIV-related causes.  

In the Philippines, people living with HIV were estimated to be at 140,000 in 2021, at 520,000 in Thailand in 2021, at 540,000 in Indonesia, and at 87,581 (77,910-98,007) in Malaysia in 2019. A cumulative total of 10,785 HIV cases have been recorded in Hong Kong in 2021, with a median age of 37 years (30-39 years old in males; 40-49 years old in females), 83% of which are males. 

Pathophysiology

The hallmark of HIV infection is CD4+ T cell destruction. The outer viral membrane which contains the HIV-specific glycoproteins (gp) including gp120 and gp41 facilitates attachment and entry of HIV into the host’s CD4+ cells. Viral replication progresses with the presence of 2 key enzymes, namely reverse transcriptase, and integrase. Reverse transcriptase transcribes viral RNA to viral DNA. After which integrase transports the viral DNA into the nucleus to be integrated into the human chromosomal DNA. In HIV infection, B cell proliferation and abnormal antibody production impairs humoral immunity. The ongoing viremia with proinflammatory cytokines, B cell proliferation, and hypergammaglobulinemia leads to a chronic inflammatory state that contributes to cardiovascular disease, cancer, and other chronic diseases. 

Classification

Types of HIV Epidemics  

Low-level epidemic occurs when HIV may have existed for many years but has never spread to significant levels in any subpopulation. Additionally, the recorded infection is largely confined to high-risk individuals (eg drug injectors, sex workers, men having sex with other men [MSM]). Lastly, HIV prevalence has not consistently exceeded 5% in any subpopulation. In a concentrated HIV epidemic, HIV has spread rapidly in a defined subpopulation but is not well established in the general population. In this case, the HIV prevalence is consistently >5% in at least one subpopulation but is <1% in pregnant women in urban areas. Lastly, generalized HIV epidemics occurs when HIV is firmly established in the general population and HIV prevalence is consistently >1% in pregnant women.  

Primary HIV Infection (PHI)  

PHI is considered after high-risk exposure within the previous 6 weeks, with virus detected in the plasma (p24 antigen [Ag] and/or HIV RNA) and/or with evolving anti-HIV antibody reactivity (negative or indeterminate to positive), with or without clinical symptoms.  

Classification of PHI  

Acute HIV Infection  

HIV RNA or p24 Ag is detectable in the setting of a negative or indeterminate HIV antibody test result.  

Recent HIV Infection  

HIV antibody is detectable up to 6 months after infection. The antibody seroconversion can affect the presence of antibodies making viral RNA detectable even after 6 months or within one’s lifetime.  

HIV Infection Stage Based on Western Blot or Immunoblot Pattern  

Stage I  

Stage I is characterized by positive HIV RNA only. The median viral load is 2,000 copies/mL. Approximately 10% of people living with HIV have <100 copies/mL.  

Stage II  

Stage II is characterized by a positive HIV RNA and p24 Ag only. The HIV RNA level is >10,000 copies/mL.  

Stage III  

Stage III is characterized by a positive HIV RNA, p24 Ag, and anti-HIV antibody by immune assay, without any specific Western Blot bands.  

Stage IV  

Stage IV is characterized by a positive HIV RNA, p24 Ag, and anti-HIV antibody by immune assay, with indeterminate Western Blot pattern.  

Stage V  

Stage V has a positive HIV RNA, p24 Ag, and anti-HIV antibody by immune assay, with a reactive Western Blot pattern but lacks p31 reactivity.  

Stage VI  

Stage VI is positive for HIV RNA, p24 Ag, and anti-HIV antibody immune assay, with a full Western Blot reactivity including a p31 band.  

Clinical Staging of HIV Disease in Adults and Adolescents  

It must be remembered that HIV disease staging and classification systems are critical tools for providing clinicians and patients with important information about HIV disease stage and clinical management. The 2 major classification systems that are currently in use are The United States (U.S.) Centers for Disease Control and Prevention (CDC) classification system and the WHO Clinical Staging and Disease Classification System. This is the assessment tool used when HIV infection has been confirmed by HIV antibody testing and serves to guide decisions on when to initiate ART.  

Clinical Stage 1  

Patients in clinical stage 1 are asymptomatic but may have persistent generalized lymphadenopathy.  

Clinical Stage 2  

In clinical stage 2, there are recurrent oral sores, unexplained weight loss (approximately <10% of the estimated or actual body weight), angular cheilitis, pruritic popular lesions, seborrheic dermatitis, recurrent respiratory tract infections (eg tonsilitis, pharyngitis, otitis media, sinusitis), fungal nail infections, and herpes zoster.  

Clinical Stage 3  

Patients in clinical stage 3 may suffer from unexplained severe weight loss (>10% of estimated or measured body weight), unexplained persistent fever (intermittent or constant) lasting >1 month, unexplained diarrhea lasting for >1 month, unexplained neutropenia (<0.5 x 10⁹/L), anemia (<8 g/dL), and/or chronic thrombocytopenia (<50 x 10⁹/L), oral hairy leukoplakia, persistent candidiasis, acute necrotizing stomatitis, gingivitis or periodontitis, pulmonary TB and severe bacterial infection (eg pneumonia, empyema, meningitis, pyomyositis, bone and joint infection, bacteremia, severe pelvic inflammatory disease).  

Clinical Stage 4  

Clinical stage 4 is characterized by HIV wasting syndrome, recurrent bacterial pneumonia, extrapulmonary TB, cytomegalovirus (CMV) disease, Kaposi’s sarcoma, disseminated mycosis, recurrent septicemia, disseminated nontuberculous mycobacterial infection, lymphoma, progressive multifocal leukoencephalopathy (PML), HIV encephalopathy, Pneumocystis jirovecii, chronic herpes simplex (urolabial, genital, anorectal of >1 millimeter or visceral at any site), esophageal candidiasis (trachea, bronchi, lungs), central nervous system (CNS) toxoplasmosis, extrapulmonary cryptococcosis including meningitis, chronic cryptosporidiosis, chronic isosporiasis, disseminated mycosis (histoplasmosis, coccidiomycosis), recurrent septicemia (including nontyphoidal Salmonella), lymphoma (cerebral or B cell non-Hodgkin), invasive cervical carcinoma, atypical disseminated leishmaniasis, and symptomatic HIV-associated nephropathy (HIVAN) or HIV-associated cardiomyopathy.