Co-receptor inhibitors

To enter an uninfected CD4 T-cell, HIV uses the CD4 receptor and either chemokine receptor 5 (CCR5) or chemokine receptor 4 (CXCR4). Viral chemokine use is generally related to immune status. In early stage HIV infection, almost all HIV is CCR5-tropic, sometimes referred to as R5 virus. In patients with more advanced HIV infection, about half will have X4 virus (HIV that uses the CXCR4 co-receptor) or dual-/mixed-tropic virus.1 2

Dual-tropic virus can use either CCR5 or CXCR4. Some individuals carry HIV variants that use CCR5 and others that use CXCR4; this is referred to as mixed tropism.

Although some experts have expressed concern that use of a CCR5 antagonist might encourage the emergence of potentially more aggressive CXCR4-using virus or dual-/mixed-tropic virus, it is not yet clear whether this will be a major problem.

One other concern is that a mutation in gp120 might allow virus to bind to the CCR5 receptor, despite the presence of an antagonist designed to block receptor use. In vitro, this occurs by accumulating two to four sequence changes in the gp120 V3 region and a non-V3 pathway is known of as well.3 

CXCR4-tropic strains have generally been linked with more rapid disease progression, though some studies suggest that the presence of CXCR4-tropic virus does not adversely affect the outcome of antiretroviral therapy.4 5

For further information on co-receptors and viral tropism, see Receptors, co-receptors and immunity to HIV in How the immune system works.


  1. Moore JP et al. The CCR5 and CXCR4 coreceptors--central to understanding the transmission and pathogenesis of human immunodeficiency virus type 1 infection. AIDS Res Hum Retroviruses 20(1):111-126, 2004
  2. Hunt PW et al. Prevalence of CXCR4 tropism among antiretroviral-treated HIV-1-infected patients with detectable viremia. J Infect Dis 196(2): 328-329, 2007
  3. Moore JP and Kuritzkes DR A pièce de resistance: how HIV-1 escapes small molecule CCR5 inhibitors. Curr Opin HIV AIDS 4(2):118-24, 2009
  4. Brumme ZL et al. Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of antiretroviral-naive individuals. J infect Dis 192: 466-474, 2005
  5. Moyle G et al. Epidemiology and predictive factors for chemokine receptor use in HIV-1 infection. J Infect Dis 191: 866-872, 2005
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.