Our study is one of the larger cohort studies performed to date and the first cohort study in Australia, to report presumed sexual transmission of HCV among HIV-infected MSM who do not inject drugs. Our study suggests that HIV positive MSM who have never IDU have a low but significant risk of HCV infection of about half a percent per year. Our data supports reports from other studies from the UK [6
], Switzerland [7
] and Amsterdam [9
] which also report presumed sexual transmission in about 1 percent of HIV-infected MSM per year.
There are four published cohort studies of the incidence of HCV among HIV-infected MSM without other recognized HCV risks where it was possible to calculate an incidence per 100 person years. In the UK [6
] a study of 308 HIV infected MSM with 1190 PY of follow up reported an incidence of 0.92/100PY. In Switzerland [7
] a study of 1571 HIV infected MSM who reported unsafe sex (n = 414) reported an incidence of 0.7/100PY (95% CI 0.3-1.4). In Amsterdam [9
] a study of 1836 MSM including 504 HIV infected MSM (between years 2000-2003) with 572 PY of follow up reported an incidence of 0.87/100PY (95% CI 0.28-2.03). An Australian study [10
] of 159 HIV infected MSM with 238 PY of follow up reported no cases of HCV infection although these findings are consistent with our study because the upper limit of their 95% confidence interval was 1.54/100 PY that includes our point estimate of 0.6/100 PY.
There are three published cohort studies of the incidence of HCV among HIV negative MSM without other recognized HCV risks where it is possible to calculate an incidence per 100 person years. In the UK [18
] a study of 948 HIV negative MSM who were not IDU, with 3335 PY of follow up reported an incidence of 0.15/100PY(95% CI 0.05-0.35). In Australia, a study [10
] among 1383 HIV negative MSM with 4412 PY of follow up reported an incidence of 0.11/100 PY (95% CI 0.03-0.26) and only one of 5 HCV positives reported injecting drug use. In Canada a study [19
] of 1053 HIV-negative MSM without other risks for HCV transmission with 2610PY of follow up reported no cases with upper limit of 95% confidence interval 0.14/100PY.
There are five published studies where it was either not possible to calculate a specific incidence of HCV among either HIV-positive or HIV-negative MSM who were not injecting drugs. In France [8
], 4 cases of HCV occurred in 252 HIV-infected MSM whose follow up time was not specified although among the entire cohort of 402 HIV-positives the median follow up of 36 months. A study with 20 years of data from 12 cohorts in the CASCADE collaboration [20
] 216 cases occurred among 3014 HIV-infected MSM, although data on drug injecting status was not presented. In Germany [21
] a study among MSM with 10199 PY of follow up reported an incidence of between 0.36-1.05/100 PY although again the incidence according to drug injecting status was not presented. A study from Denmark [22
] in the 1980s documented HCV transmission in 250 MSM without other risks but the HIV prevalence was not given. Similarly an Italian study [23
] of 244 MSM without IDU documented an incidence of 1.37/100 PY, but again there was no information on HIV prevalence.
The most common reason for HCV testing among HCV positive individuals in our study was the development of abnormal liver function tests. There were seven cases identified through routine screening for HCV that only began in 2008 and it is possible that among these seven cases, infection had occurred significantly earlier. This bias is evident in the survival curve with the increase in gradient of the curve at about 200-300 months of follow up, but would have only had a minor effect on the incidence estimate. The data do however suggest that routine monitoring of liver function tests will identify the majority of cases of even asymptomatic HCV infection. This finding supports a recent study in the UK [24
] where elevated liver enzymes were the most common reason for HCV diagnosis. Another study [25
] among HIV positive MSM showed testing for ALT was more sensitive than HCV antibody testing for early diagnosis of HCV. However given the importance of early treatment of HCV diagnosis, clinicians should not rely only on elevations of routine liver function tests because they will miss a significant minority of cases.
Routine testing for hepatitis C among MSM began in 2008 [17
] and since then, of the 444 HIV-positive HCV-negative MSM who were having bloods drawn at least once a year at our clinic, 75% (n = 332) had subsequent HCV serology. It would be helpful to put the rates of Hepatitis C infection described in our study in context with the rates of other STI in MSM in Victoria. In a study looking at the proportion of samples positive for gonorrhoea and chlamydia by anatomical site between 2002 to 2009 at our centre in MSM, no increase in either infection was noted however there was a suggestion that the proportion of samples positive for gonorrhoea may be falling (Vodstrcil LA, Fairley CK, Fehler G, Leslie D, Walker J, Bradshaw C, Hocking JS: Trends in Chlamydia and Gonorrhoea Positivity among Heterosexual Men and Men who have sex with Men attending a sexual health service between 2002 and 2009, submitted). In contrast rates of syphilis have risen significantly over this time in MSM [26
]. The first case of anorectal LGV was detected in a MSM, Victoria in 2005 [28
] and since then 18 have been diagnosed in MSM with HIV at MSHC until March 2010.
Our study had a number of weaknesses. Firstly it was retrospective and therefore excluded some individuals from the analysis who were either never tested for HCV and were HCV positive when first tested. If the incidence of HCV among those never tested was very high then we would have underestimated the true incidence. Conversely if the HCV incidence among those never tested was very low then we would have overestimated the true incidence. Our estimate would have also underestimated the true incidence if a significant proportion of those whose first HCV test was positive were true incident cases. If we included all of the 41 cases positive on their first tests it would have only increased the incidence among MSM who were non-IDU from about 0.6/100 PY to 1.7 per 100 PY. Given that the objective was to compare the incidence rates between members of the HIV positive MSM cohort who did and did not engage in IDU, we thought underestimating the incidence was preferred.
Our study did not collect detailed risk factor information prospectively on all members of the cohort and therefore this information may be incomplete, particularly in relation to the possible risk factors for sexual transmission of HCV infection. We are therefore unable to look at hazard ratios for different sexual exposures (e.g. fisting) in our study. However analysis of sexual risk was not the primary aim of the study and is an acknowledged weakness although other investigators have reported that unprotected traumatic anal sex, bleeding during sex, fingering, fisting, rimming, and number of recent sexual partners are risks for possible sexual transmission [6
Under-reporting of IDU may have also biased our study. Previous studies in Australia have shown however the social desirability bias (e.g. under reporting of IDU) is uncommon in Australia compared to the US or UK [30
]. Furthermore those who tested positive for HCV had generally been attending the centre's service and seeing the same clinician for years (mean attendance 5 years) and were therefore likely to have established good rapport with their clinicians.