Primary infection and sexual transmission

Published: 12 August 2013
  • During untreated primary HIV infection, people have exceptionally high viral loads and are extremely infectious.
  • However, primary infection only lasts a few weeks or months, so there are fewer opportunities for transmission than during many years of chronic infection.
  • People who frequently change sexual partners are more likely to have sex with someone with high viral loads during primary infection.
  • It is estimated that half of new infections in gay men and other men who have sex with men in the UK are acquired from men with undiagnosed primary HIV infection.

During untreated primary HIV infection, people have exceptionally high viral loads and are extremely infectious. However, primary infection only lasts a few weeks or months, so there are fewer opportunities for transmission than during many years of chronic infection. The opportunities for transmission are therefore lower compared with untreated chronic HIV infection, which can last for years or even decades.

However, there is currently some disagreement regarding the impact of untreated primary (also called acute) HIV infection versus untreated chronic HIV infection on infectiousness and sexual transmission, and their relative contributions to new HIV infections, with estimates of transmission following primary infection ranging from a low of 9% to a high of almost 50%.

The impact has been found to vary according to the characteristics of the population studied, such as the rate of partner change, the proportion of HIV transmitted in stable couples and the proportion transmitted during casual sex.

For example, a modelling study suggests that in 2010 48% of all new infections in gay men and other men who have sex with men in the UK were acquired from men with undiagnosed primary HIV infection. This compares with 34% acquired from men with undiagnosed chronic infection, 10% from men who were diagnosed but not on treatment, and 7% from men on treatment.1

In contrast, modelling from the United States, examining heterosexual and homosexual transmissions estimated that fewer than 9% of new infections originated in people with untreated primary HIV infection. Far more came from people with untreated chronic HIV infection.2

Key studies

Studies in Uganda3 and the United States4 established that viral load during untreated primary HIV infection is much higher – and therefore individuals are more infectious – than during untreated chronic infection.

A prospective study in heterosexual couples in Rakai, Uganda,where one partner was HIV-positive at the start of the study, and one partner HIV-negative, showed that the likelihood of heterosexual HIV transmission is highest in the first two and a half months following initial infection with HIV, and that this correlated with higher viral load levels in early HIV infection.5

The investigators estimated that 43% of transmissions in the study occurred within ten weeks of the index partner’s infection. They also estimated that primary HIV infection increased the risk of HIV transmission per sexual act more than seven-fold compared to the risk of HIV transmission per sexual act during the chronic (and longest) period of untreated HIV infection. A second analysis of these data6 estimated that relative to chronic infection, infectiousness during primary infection was actually enhanced 26-fold (and 3.6-fold during late/end-stage infection).

However, taking into account primary infection’s relatively short duration, they concluded that 14% of onward transmission occurred during primary infection, compared with 46% during the chronic stage and 40% during end/late-stage HIV disease.

Similarly, a 2007 US mathematical modelling studyestimated that fewer than 9% of all new sexually transmitted HIV infections originated in people with untreated primary HIV infection, compared with 48% of new infections resulting from sexual contact with people with untreated chronic HIV infection.2

Although it agreed with previous studies that individuals with primary HIV infection have exceptionally high viral loads, and estimated that they were 16 times more infectious than during chronic infection, because the period for which they are highly infectious is relatively short, typically no more than 49 days, individuals with acute HIV infection only represented 0.5% of all HIV-infected individuals in the United States.

Studies in populations that include a higher proportion of gay men and other men who have sex with men (with potentially much more frequent partner change than heterosexual couples in Africa – even those with concurrent relationships), have come to different conclusions regarding the role of primary infection on new HIV infections.

A 2007 study from Quebec, Canada,used phylogenetic analysis of blood samples in Quebec’s genotypic-resistance database. It estimated that almost half of all sexually transmitted HIV infections were attributed to primary or early infection.7

However, in this study, although some onward transmission took place within a month of infection, the average time between infection and onward transmission was 15 months. The investigators found that whilst primary/early HIV infection represented just 10% of the total sequenced samples in the genotypic-resistance database, it accounted for 49% of all onward transmission events. In contrast, they found that treatment-naive and treatment-experienced chronically infected individuals accounted for 15 and 12% of onward transmission, respectively, with the other 25% uncertain.

A 2012 phylogenetic analysis study from Denmark provided further evidence that men who have only recently been infected with HIV are largely sustaining new infections amongst gay men and other men who have sex with men.8

The investigators looked at networks and clusters of HIV transmissions in the country. Approximately a fifth of people were found to have primary HIV infection, and half of all people with primary HIV infection could be placed within a transmission cluster, compared to only 22% of people whose HIV was diagnosed late. Some 40 clusters involved gay men, and the two largest transmission networks involved half of all people with primary infection.

If people are diagnosed quickly, identified as having a recent infection and begin antiretroviral therapy immediately, this can have a significant impact on viral loads and onward transmission. Clinicians in Bangkok, Thailand, developed such a programme, with most participants being diagnosed an estimated 10 to 23 days after infection. Viral loads dropped dramatically, with 55% of participants achieving an undetectable blood plasma viral load at week 8, 80% at week 16, 91% at week 24, and 97% at week 48.  Of note, seminal plasma viral load dropped to undetectable levels more rapidly – 59% were undetectable by week 2, 73% by week 4, 95% by week 12 and 100% by week 24.

It is commonly reported that risk behaviours reduce following an HIV diagnosis. Moreover, in this Thai cohort, risk reduction counselling was credited with achieving substantial behaviour change. Whereas at baseline 84% of men reported having had unprotected anal intercourse in the previous four months (including 57% with a casual partner), by week 24, the figures had dropped to 25 and 8%, respectively, with the changes sustained to week 48.

The researchers’ preliminary modelling work suggested that when an individual with acute infection receives this package of interventions, it may avert 78% of onward transmissions in the first six months after infection.9

Perhaps the most intriguing study on the relative impact of primary versus chronic infection used mathematical modelling to estimate the impact of untreated HIV infection on transmission.10

The investigators examined the link between viral load and transmission from a Zambian study of serodiscordant heterosexual couples and found that the periods of highest viral load (during primary infection and again during late-stage HIV disease) did not actually have the highest transmission potential, because these lasted relatively short periods of time. Instead, they found that the viral load with the highest transmission potential (of a hypothetical average of 1.5 infections per person per lifespan) was found to be during chronic infection.

The study concluded that the 'ideal' viral load for HIV in its 'quest' for continued survival was 33,113 (4.52 log10) copies/ml. At this viral load, someone could live for around ten years without becoming ill and still feel well enough to have sex, providing HIV with the longest transmission potential. The investigators hypothesise that HIV may have actually evolved so that average viral loads during chronic infection are finely balanced between being the optimal for HIV transmission and the optimal for human survival.

References

  1. Phillips AN Increased HIV Incidence in Men Who Have Sex with Men Despite High Levels of ART-Induced Viral Suppression: Analysis of an Extensively Documented Epidemic. PLoS ONE 8(2): e55312. doi:10.1371/journal.pone.0055312, 2013.
  2. Pinkerton SD et al. How many sexually acquired HIV infections in the USA are due to acute-phase HIV transmission? AIDS 21:1625-1629, 2007
  3. Quinn TC et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med 342(13): 921-929, 2000
  4. Pilcher CD et al. Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis 189(10):1785-1792, 2004
  5. Hollingsworth TD et al. HIV-1 Transmission, by Stage of Infection. J Infect Dis 198(5):687-693, 2008
  6. Wawer MJ et al. Rates of HIV-1 transmission per coital act by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis 191: 1403-1409, 2005
  7. Brenner BG et al. High rates of forward transmission events after acute/early HIV-1 infection. J Infect Dis 195: 951-959, 2007
  8. Audelin AM et al. Phylogenetics of the Danish HIV epidemic: the role of very late presenters in sustaining the epidemic. J Acquir Immune Defic Syndr, online edition, DOI: 10.1097/QAI.0b013e318276becc, 2012
  9. van Griensven F et al. (Presented by Kroon E) Acute HIV infection detection and control reduces HIV infectiousness and transmission risk behavior among men who have sex with men in Bangkok, Thailand. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Kuala Lumpur, abstract WELBC03, 2013
  10. Fraser C et al. Variation in HIV-1 set-point viral load: Epidemiological analysis and an evolutionary hypothesis. Proc Natl Acad Sci epub Oct 22, 2007
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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.