Close link between HIV and hepatitis C transmission networks

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HIV and hepatitis C virus (HCV) transmission networks are closely linked, according to Swiss research published in the International Journal of Epidemiology. Combining clinical data with phylogenetic analysis of HIV samples from a drug resistance database showed that the risk of incident HCV infection was increased by a factor of two if a patient was “clustered” with another patient with HCV.

“Our results indicate that the transmission networks of HIV and HCV are correlated and overlap even beyond the degree that can be expected by demographic variables such as risk group…geography, sex and age,” comment the authors. “Thus, our analysis shows that the location of an HIV-infected patient on the HIV phylogeny can serve as an indicator for the risk of an HCV coinfection.” They believe their findings have important implications for HCV prevention efforts, allowing the identification of people with an especially high risk of infection.

HIV and HCV can both be acquired by contact with blood. There is also an ongoing epidemic of sexually transmitted HCV among HIV-positive gay men. A significant proportion of people living with HIV therefore have hepatitis C co-infection, and liver disease is an important cause of serious illness and death in this group.

Glossary

IDU

Injecting drug user.

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

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.

subtype

In HIV, different strains which can be grouped according to their genes. HIV-1 is classified into three ‘groups,’ M, N, and O. Most HIV-1 is in group M which is further divided into subtypes, A, B, C and D etc. Subtype B is most common in Europe and North America, whilst A, C and D are most important worldwide.

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.

However, the extent to which HIV and HCV transmission networks overlap is uncertain. A clearer understanding of this issue could assist in the development of targeted HCV prevention campaigns.

Investigators therefore obtained information on HCV infection status for people enrolled in the Swiss HIV Cohort Study (SHCS). This was combined with information on HIV and HCV risk group – injecting drug use (IDU), heterosexual, men who have sex with men (MSM), heterosexual/IDU, or MSM/IDU. The investigators then examined 15,000 blood samples obtained from 10,000 people in the SHCS HIV drug resistance database. A technique called phylogenetic analysis allowed them to construct HIV transmission pairs. Linking clinical and phylogenetic data enabled the investigators to examine the interaction between the spread of HIV and HCV.

A total of 2768 people (28%) had at least one positive HCV test and were classified as having prevalent HCV infection. A further 208 individuals (2%) had a first negative HCV test and a subsequent positive result. These patients were classified as having incident HCV infection.

Prevalence differed according to risk group. It was highest among injecting drug users (95%), heterosexual/IDU (72%) and MSM/IDU (27%), but much lower in MSM (5%) and heterosexuals (6%).

Phylogenetic analysis was restricted to the 7644 people in the drug resistance database with HIV subtype-B infection. A total of 1555 possible HIV transmission pairs were identified in which the HCV status was known for both members. In 907 of these pairs both members were HCV-negative; in 303 one member was HCV-infected and in 345 both were HCV-positive.

The risk of HCV co-infection was significantly increased if the other patient in the pair had HCV co-infection as well (OR = 13.6; 95% CI, 10.5-17.6). This extremely high risk was due to the clustering of IDUs with other IDUs.

However, an association between the HCV status of individuals in transmission pairs persisted when risk groups were considered separately.

After adjusting for factors including sex, age and transmission group, the authors found that people in HIV transmission pairs were much more likely to be HCV infected if their partner in the pair was also HCV-positive (OR = 3.2; 95% CI, 2.2-4.7).

“We observed a strong clustering of prevalent HCV cases on the HIV phylogeny even after controlling for the most important demographic confounders,” comment the authors.

Similarly, initially HCV-negative individuals were more likely to become infected with HCV if they belonged to a transmission pair where their partner was HCV-positive (HR = 2.1; 95% CI, 1.1-3.8). This finding persisted when the investigators restricted their analysis to incident HCV infections in MSM (HR = 2.29; 95% CI, 0.9-5.4).

“This suggests,” write the authors, “that the observed doubling of HCV incidence in individuals clustering with HCV-coinfected partners on the HIV phylogeny was, at least in part, mediated through sexual transmission of HCV.”

They conclude that people whose HIV is closely related to a patient co-infected with HCV have a higher risk of becoming infected with HCV. These patients “could constitute target groups where intensified testing and counselling are particularly important.”

References

Kouyos RD et al. Clustering of HCV coinfection on HIV phylogeny indicates domestic and sexual transmission of HCV. Int J Epidemiol, online edition. doi.10.1093/ije/dyt276, 2014.

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