The human immunodeficiency virus (HIV) is the retrovirus that causes acquired immunodeficiency syndrome (AIDS). It exists in two distinct forms: HIV-1 and HIV-2. HIV-1 is responsible for the global pandemic and the vast majority of cases worldwide, while HIV-2 is a separate, less common type that also causes a chronic infection. Both viruses belong to the lentivirus family, a group of slow-acting retroviruses that attack and weaken the body’s immune system by targeting CD4 T-helper cells. Despite causing the same ultimate effect of immunodeficiency, HIV-1 and HIV-2 are genetically and clinically different, requiring unique considerations for diagnosis and treatment.
Defining Characteristics and Origin
HIV-2 is genetically distinct from HIV-1, sharing only about 55% of its genetic sequence identity with the more prevalent strain. This difference means that not all diagnostic tests and treatments designed for HIV-1 are effective against HIV-2. The virus is categorized into eight groups (A through H), with groups A and B being the primary types responsible for the majority of human infections.
The origin of HIV-2 is a result of a zoonotic, or cross-species, transmission event from non-human primates to humans. HIV-2 is closely related to the Simian Immunodeficiency Virus (SIV) found in sooty mangabeys, an Old World monkey species native to West Africa. Phylogenetic analysis indicates that multiple independent transmissions from SIV-infected sooty mangabeys gave rise to the different HIV-2 groups. This distinct evolutionary path explains the fundamental biological differences between HIV-2 and HIV-1, which originated from SIV in chimpanzees.
Geographic Distribution and Transmission
The vast majority of HIV-2 infections are concentrated in West Africa, where the virus is endemic, particularly in countries like Senegal, Guinea-Bissau, and Côte d’Ivoire. Cases have been reported globally, including in Europe, India, and the Americas, mostly linked to migration and travel from West Africa. This geographic concentration means HIV-2 accounts for less than 5% of global HIV cases, making it far less common than HIV-1.
HIV-2 is transmitted through the same routes as HIV-1: sexual contact, exposure to infected blood, and mother-to-child transmission. However, the efficiency of transmission for HIV-2 is notably lower than for HIV-1. For example, the rate of mother-to-child transmission for untreated HIV-2 is significantly lower than for untreated HIV-1, likely due to the lower viral loads typically seen in people with HIV-2.
Distinct Clinical Progression Compared to HIV-1
The clinical course of HIV-2 infection is characterized by a slower progression to acquired immunodeficiency syndrome (AIDS) compared to HIV-1. People with HIV-2 often experience a longer asymptomatic period, which can last for years or decades. This reduced rate of disease progression is linked to the virus’s generally lower viral loads, meaning the amount of viral particles in the blood is substantially lower than in HIV-1 infection.
A significant portion of individuals infected with HIV-2 may never progress to AIDS, even without antiretroviral therapy. The body’s immune response to HIV-2 appears to be more effective and protective, limiting the virus’s ability to replicate and cause widespread damage to CD4 T-cells. Researchers note that the immune response tends to be more robust, suggesting that immune factors limit the viral pathology.
Plasma viral loads in HIV-2 are consistently lower, often measured at levels approximately 28-fold less than those seen in HIV-1 infections. This low viral presence means that the depletion of CD4 T-cells occurs at a slower rate, allowing the immune system to maintain its function longer. Despite this slower course, HIV-2 is still a serious infection that can ultimately lead to AIDS and death if left untreated.
Diagnosis and Management
Diagnosing HIV-2 requires specific testing because the genetic difference means a test designed only for HIV-1 will not reliably detect HIV-2. Modern screening protocols use combination tests that look for both HIV-1 and HIV-2 antibodies, as well as the HIV-1 p24 antigen. If the initial screening test is reactive, a follow-up differentiation immunoassay confirms the infection and distinguishes between HIV-1, HIV-2, or a dual infection.
The management of HIV-2 infection involves antiretroviral therapy (ART), similar to HIV-1, but drug regimens must be carefully tailored. HIV-2 is naturally resistant to a major class of HIV-1 drugs known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). This intrinsic resistance is due to structural differences in the reverse transcriptase enzyme, preventing NNRTI drugs from binding effectively.
Therefore, treatment for HIV-2 cannot include NNRTIs like efavirenz or nevirapine. Recommended first-line ART regimens typically consist of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a third drug. This third drug is usually an integrase strand transfer inhibitor (INSTI) or a boosted protease inhibitor (PI). Integrase inhibitors, such as dolutegravir, have demonstrated effectiveness against HIV-2, and certain PIs like darunavir are preferred options in combination with two NRTIs.