Recent infection, high viral load and STIs mean higher risk of onward HIV transmission for gay men

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Recent HIV infection, sexually transmitted infections, and a higher blood viral load are associated with a higher risk of onward HIV transmission in gay men, according to research conducted in Brighton and presented to the recent Sixteenth Conference on Retroviruses and Opportunistic Infections in Montreal.

The researchers used phylogenetic, clinical and epidemiological data to model the transmission of HIV. Use of HIV treatment was associated with a significantly reduced risk of HIV transmission, but they found that many cases of transmission originated in men whose HIV had not been diagnosed. Furthermore, the investigators found two possible cases of HIV transmission involving individuals who apparently had an undetectable viral load.

There continue to be large numbers of new HIV infections in gay and other men who have sex with men. Such transmissions are continuing despite the availability of effective HIV treatment that not only improves the health of the individual but can, buy lowering viral load, also reduce the risk of HIV transmission.

Glossary

phylogenetic analysis

The comparison of the genetic sequence of the virus in different individuals in order to determine the likelihood that two or more samples are related. This involves creating a hypothetical diagram (known as a phylogenetic tree) that estimates how closely related the samples of HIV taken from different individuals are. Phylogenetic analysis is not a reliable way to prove that one individual has infected another, but may identify transmission clusters, which can be useful for public health interventions.

epidemiology

The study of the causes of a disease, its distribution within a population, and measures for control and prevention. Epidemiology focuses on groups rather than individuals.

risky behaviour

In HIV, refers to any behaviour or action that increases an individual’s probability of acquiring or transmitting HIV, such as having unprotected sex, having multiple partners or sharing drug injection equipment.

opportunistic infection (OI)

An infection that occurs more frequently or is more severe in people with weakened immune systems, such as people with low CD4 counts, than in people with healthy immune systems. Opportunistic infections common in people with advanced HIV disease include Pneumocystis jiroveci pneumonia; Kaposi sarcoma; cryptosporidiosis; histoplasmosis; other parasitic, viral, and fungal infections; and some types of cancer. 

viraemia

The presence of virus in the blood.

 

Recent infection with HIV and untreated sexually transmitted infections are thought to be factors associated with an increased risk of HIV transmission. There is also some evidence to suggest that a substantial number of HIV infections originate in patients whose HIV is undiagnosed.

Studies in heterosexuals have shown the association between higher viral load and an increased risk of transmission and the disproportionate contribution that recently infected individuals make to the continued spread of HIV. Evidence from heterosexual couples has also demonstrated that HIV treatment can reduce the risk of HIV transmissions. However, researchers have been cautious about applying these findings to gay men.

Researchers in Brighton therefore used phylogenetics, clinical and epidemiological information to identify the factors involved in new HIV infections in gay men.

The study population involved 1144 gay men attending an HIV treatment centre in Brighton between 2000 and 2004. Individuals were monitored every three months and categorised as having recent or chronic HIV infection. Information was also gathered on viral load, CD4 cell count, sexually transmitted infections, and use of HIV treatment.

It was possible to perform phylogenetic analysis on the HIV from 859 individuals, 19% (159) had recent HIV infection. A total of 47 (29%) of these recent infections were identified as being part of a cluster of transmissions.

Using phylogenetic analysis, a single likely transmitter of HIV was identified in 41 cases. Ten of these transmitters (24%) were recently infected with HIV. This finding suggested to the investigators that “a significant proportion of new infections originate from individuals with undiagnosed infection”.

There was also clear evidence of an association between a higher viral load and a greater risk of HIV transmission. Each log10 increment in viral load increased the risk of HIV transmission by 61% (p = 0.007).

When the investigators looked in more detail at the viral loads of the 41 known transmitters, they found that 29 had a viral load above 10,000 copies/ml at the time transmission is thought to have occurred. Nevertheless, two patients had an undetectable viral load at the time of transmission, but in one of these patients the previous viral load was above the limit of detection, so the investigators suggest “transmission may actually have occurred with detectable viraemia [viral load]”.

Taking HIV treatment was associated with a 96% reduction in the risk of HIV transmission (p = 0.0001). “This finding supports the assertion that the widespread use of antiretroviral therapy may result in decreased transmission,” write the investigators.

However, they note that 70% of the identified 41 transmitters had never taken HIV treatment, leading the investigators to suggest “earlier initiation of antiretroviral therapy than currently recommended within treatment guidelines may be required” for HIV treatment to have a population-wide impact on the continued spread of HIV.

Nine of the 41 patients transmitting HIV had interrupted their HIV treatment at the time transmission occurred. “Unless accompanied by changes in risk behaviour, treatment interruption may be associated with increased onwards transmission. Clinicians need to highlight this with individuals considering stopping antiretroviral therapy”, write the investigators.

A recent sexually transmitted infection increased the risk of HIV transmission by 181% (p = 0.0001), supporting the findings of earlier research.

There have been a number of prosecutions and convictions for ‘reckless’ HIV transmission in the UK. Individuals who did not inform their partner(s) they were HIV-positive and had unprotected sex leading to HIV transmission have received lengthy prison sentences. Many of these convictions relied on guilty pleas after the accused was presented with phylogenetic evidence that the prosecution said ‘proved’ they were the source of the infection.

However, it has been shown in court that phylogenetic analysis cannot prove an individual was the source of the infection.

No doubt with these cases in mind, the investigators write “like other phylogenetic studies, transmission cannot be proven – i.e. it is not possible to say that person A infected person B rather than a third party, person C, infecting both or an intermediary.”

References

Fisher M. et al. HIV transmission amongst men who have sex with men: association with antiretroviral therapy, infection stage, viraemia and STDs in a longitudinal phylogenetic study. Sixteenth Conference on Retroviruses and Opportunistic Infections, abstract, 2009.