Dr. Jim Shelton's Pearls: Low Infectiousness in Chronic Phase of HIV Infection
Dr. Jim Shelton's Pearls is an occasional series by USAID’s Global Health Science Advisor that answers commonly asked questions about family planning.
Originally posted on March 8, 2010.
Question: That’s very interesting that during the chronic phase of HIV infection genital transmission risk is relatively low. Why would that be?
- Immune response producing low viral load in the infected person. After the phase of acute infection, the body’s immune system kicks in and reduces viral loads and genital secretion of virus to very low levels. This is widely accepted as the key reason for reduced transmission. (These low levels tend to remain until the final advanced phase when the immune system starts to fail, though some events like STI’s may induce spikes in viral load and genital shedding.)
- Some immunity in the exposed but uninfected person. There is evidence that some people develop some immunity that is associated with decreased risk of acquisition (e.g. a type of immunity called mucosal immunity, generating neutralizing antibodies.)
- Selection over time for reduced propensity for infection. There is some natural variation both in the infectiousness of certain infected people and in the susceptibility of others to becoming infected. Over time, partnerships with the most propensity for transmission tend to produce infections, leaving those with less propensity for transmission to become a higher proportion of the exposed population. Similarly there are behavioral factors such as sexual practice and frequency, such that those at highest risk are infected first. As a consequence, couples with lower infectivity/susceptibility may be overrepresented in observational studies.
- Changes in the virus in the host over time. It is quite clear that the “founding” virus that causes initial infection changes in the host markedly over time. Through high rates of replication and mutation, differential survival in response to strong immune response leads to a family of variant virus forms. Only certain virus variants appear likely to be founder viruses. It appears plausible that some of that change for survival in the host might make the virus less transmissible from one person to the next. For example speculatively, it appears the virus develops something of a different/thicker outside envelop coating to evade the immune system, which might make it more difficult to travel through transmitting and receiving genital mucosa/environment to cause a new infection. (However, it is also known that the body retains smaller reservoirs of earlier virus forms that could later be released.)
Note. Even though transmission during the chronic phase is relatively low, it is still appreciable. Risk reduction for individuals who are HIV+ and for their partners in any stage of infection is clearly an important priority.
- Hirbod T et al. HIV-Neutralizing immunoglobulin A and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan Sex workers. AIDS 2008; 22:727-735.
- Sagar M et al. Selection of HIV variants with signature genotypic characteristics during heterosexual transmission. JID 2009; 199:580-589.