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Infectious Disease and Microbiology: HIV Infection
Human immunodeficiency virus (HIV) infection is a chronic viral disease that progressively impairs the immune system, primarily through destruction and dysfunction of CD4+ T lymphocytes. Without treatment, it can lead to acquired immunodeficiency syndrome (AIDS), the advanced stage of infection characterized by severe immunosuppression, opportunistic infections, malignancies, and death. HIV-1 is the predominant type worldwide, while HIV-2 is found mainly in West Africa and generally causes slower disease progression.
HIV remains a major global health problem, affecting millions of individuals worldwide. In the United States alone, more than one million people are living with HIV, with tens of thousands of new infections occurring annually. Transmission occurs through sexual contact, blood exposure such as needle-sharing or occupational exposure, and mother-to-child transmission during pregnancy, delivery, or breastfeeding. The risk of transmission varies by route, with blood exposure and receptive anal intercourse carrying higher risks than other exposures. Advances in antiretroviral therapy (ART) and perinatal management have markedly reduced maternal–fetal transmission.
The virus is a retrovirus of the lentivirus family. It binds to CD4 receptors and co-receptors on host lymphocytes, enters the cell, and uses reverse transcriptase to convert viral RNA into DNA. This viral DNA integrates into the host genome, allowing lifelong infection. Subsequent activation of infected cells leads to production of new viral particles, which destroy CD4 cells and gradually weaken cellular immunity. This immune dysfunction predisposes patients to a wide range of infectious and noninfectious complications.
Clinically, HIV infection progresses through several stages. Acute HIV infection may occur within weeks of transmission and often presents with a nonspecific viral syndrome including fever, pharyngitis, rash, myalgias, lymphadenopathy, diarrhea, and headache. This is followed by an asymptomatic phase that may last many years, during which viral replication continues and CD4 counts slowly decline. Symptomatic HIV infection develops as immunosuppression worsens and may include recurrent mucocutaneous infections, weight loss, fevers, and eventually opportunistic infections such as Pneumocystis jirovecii pneumonia, cryptococcal meningitis, toxoplasmosis, cytomegalovirus disease, and Mycobacterium avium complex infection. HIV is also associated with malignancies such as Kaposi sarcoma, lymphoma, cervical cancer, and neurologic complications including HIV-associated neurocognitive disorder.
Diagnosis begins with screening using highly sensitive HIV antibody tests, followed by confirmatory testing. In suspected acute HIV infection, HIV RNA testing is essential because antibody tests may still be negative during early infection. Once diagnosis is confirmed, baseline evaluation includes CD4 count, HIV viral load, resistance genotype, complete blood count, renal and liver function tests, and screening for co-infections such as hepatitis A, B, and C, syphilis, tuberculosis, toxoplasmosis, cytomegalovirus, and varicella zoster. These tests help assess disease stage, identify treatment needs, and detect concurrent infections.
Treatment with antiretroviral therapy is the cornerstone of HIV management. The goals of ART are to suppress plasma HIV RNA to undetectable levels, preserve or restore immune function, reduce HIV-related complications, and prevent transmission. Standard treatment consists of combination therapy using multiple drug classes, commonly two nucleos(t)ide reverse transcriptase inhibitors together with either a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor, or an integrase strand transfer inhibitor. Choice of regimen depends on drug resistance, side effects, pill burden, co-morbidities, pregnancy considerations, and potential drug interactions. ART is generally lifelong, and adherence is critical to prevent virologic failure and resistance.
Prevention of HIV includes condom use, safe blood practices, clean needle access, screening of blood products, and routine testing, especially in pregnancy and high-risk populations. Post-exposure prophylaxis should be started as soon as possible after significant occupational or non-occupational exposure, ideally within hours and no later than 72 hours, and continued for four weeks. Pre-exposure prophylaxis has also become an important preventive strategy for individuals at substantial risk.
Ongoing care requires regular monitoring of viral load, CD4 count, medication toxicity, cardiovascular risk factors, and co-infections. Patients with advanced immunosuppression require prophylaxis against opportunistic infections, such as trimethoprim-sulfamethoxazole for Pneumocystis and toxoplasmosis, and azithromycin for Mycobacterium avium complex when indicated. Vaccination, cancer screening, and management of long-term complications are also essential parts of care.
The prognosis of HIV infection has improved dramatically with effective ART. Many patients who are diagnosed early and remain adherent to treatment can achieve near-normal life expectancy. However, treatment failure may occur due to poor adherence or drug resistance, leading to virologic, immunologic, and clinical decline. Without treatment, HIV infection remains a progressive and often fatal disease.
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