What is the difference between HIV (Human Immunodeficiency Virus) 1 and HIV 2 genotypes?

Differences Between HIV-1 and HIV-2 Genotypes

HIV-2 has natural genetic polymorphisms that confer innate resistance to certain antiretroviral drugs compared to HIV-1, making it critical to differentiate between these viruses for effective treatment. 1

Genetic Differences

• HIV-1 and HIV-2 share only about 60% of their genetic sequences, despite having similar basic gene arrangements and intracellular replication pathways 1, 2
• HIV-2 contains natural polymorphisms that confer innate resistance to first-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs), thymidine analogues, and some integrase inhibitors 1
• HIV-2 has different genotypic patterns in key viral proteins, particularly in the envelope glycoproteins, which affects viral tropism and host cell interactions 1

Epidemiological Distribution

• HIV-1 is pandemic and globally distributed, accounting for the vast majority of HIV infections worldwide 2, 3
• HIV-2 remains largely confined to West Africa, with limited international spread, and is found primarily in immigrants from or people with epidemiological links to West Africa 1
• HIV-1 subtype B accounts for only about 12% of global HIV-1 infections, while subtype C is most prevalent (approximately 50% of cases worldwide) 1

Viral Pathogenesis and Disease Progression

• HIV-2 demonstrates lower transmissibility compared to HIV-1, with heterosexual transmission of HIV-2 occurring at significantly lower rates 3, 4
• HIV-2 infected individuals typically have lower plasma viral loads compared to HIV-1, particularly during early and asymptomatic stages of infection 2, 3
• HIV-2 patients tend to have a higher CD4+ T-cell count at the time of AIDS diagnosis (median 176 cells/μl vs. 109 cells/μl in HIV-1) and longer survival after AIDS diagnosis 5
• Most HIV-2 infected individuals remain long-term non-progressors, while most HIV-1 infected individuals progress to AIDS without treatment 2

Drug Resistance Patterns

• HIV-2 has natural resistance to NNRTIs due to pre-existing polymorphisms, making these drugs ineffective against HIV-2 infection 1
• HIV-2 shows variable susceptibility to protease inhibitors, with some demonstrating reduced activity 1
• Tenofovir displays strain-specific activity against HIV-2 with EC50 values ranging from 1.6 μM to 5.5 μM, compared to 0.04 μM to 8.5 μM for HIV-1 6
• Cross-resistance patterns between HIV-1 and HIV-2 differ due to their distinct genetic structures and natural polymorphisms 1, 6

Immune Response Differences

• Cellular immune responses to HIV-2 tend to be more polyfunctional and produce more IL-2 than responses to HIV-1 2
• Humoral immune responses to HIV-2 appear broader with lower magnitude intratype neutralization responses 2
• Innate immune responses appear more robust against HIV-2, possibly through differential effects of tripartite motif protein isoform 5 alpha 2
• Overall immune activation levels are lower in HIV-2 infection compared to HIV-1 2, 7

Clinical Implications and Testing

• HIV-2 infection should be suspected in persons of West African origin with clinical conditions suggestive of HIV but atypical serologic test results (presence of viral bands but absence of envelope gp41, gp120, and gp160 on Western blot) 1
• The Multispot rapid test is FDA-approved for differentiating HIV-1 from HIV-2 infection, but confirmation of HIV-2 requires consultation with state health departments 1
• Understanding the type of HIV infection is critical for selecting appropriate antiretroviral therapy, as HIV-2 has natural resistance to certain drug classes 1
• HIV-2 may serve as a model for identifying functional HIV cure strategies due to the higher proportion of long-term viral controllers compared to HIV-1 7

Treatment Considerations

• First-generation NNRTIs should be avoided in HIV-2 treatment due to natural resistance 1
• Integrase inhibitor-based regimens, particularly dolutegravir-based therapy, may be effective against both HIV-1 and HIV-2 1
• Drug resistance testing interpretation algorithms developed for HIV-1 may not be applicable to HIV-2 due to differences in natural polymorphisms and resistance pathways 1
• In HIV-1/HIV-2 dual infection, treatment regimens must be effective against both viruses 7