Risk Of Developing Liver Cancer After HCV Treatment

Thursday, January 12, 2012

Minimal Transmission of HIV Despite Persistently High Transmission of Hepatitis C Virus in a Swedish Needle Exchange Program

From Journal of Viral Hepatitis

Minimal Transmission of HIV Despite Persistently High Transmission of Hepatitis C Virus in a Swedish Needle Exchange Program

M. Alanko Blomé; P. Björkman; L. Flamholc; H. Jacobsson; V. Molnegren; A. Widell

Authors and Disclosures

Posted: 01/10/2012; J Viral Hepat. 2011;18(12):831-839. © 2011 Blackwell Publishing

Abstract
The aim of this study was to examine the prevalence and incidence of HIV and hepatitis B and C (HBV and HCV) among injecting drug users in a Swedish needle exchange programme (NEP) and to identify risk factors for blood-borne transmission. A series of serum samples from NEP participants enrolled from 1997 to 2005 were tested for markers of HIV, HBV and HCV (including retrospective testing for HCV RNA in the last anti-HCV-negative sample from each anti-HCV seroconverter). Prevalence and incidence were correlated with self-reported baseline characteristics. Among 831 participants available for follow-up, one was HIV positive at baseline and two seroconverted to anti-HIV during the follow-up of 2433 HIV-negative person-years [incidence 0.08 per 100 person-years at risk (pyr); compared to 0.0 in a previous assessment of the same NEP covering 1990–1993]. The corresponding values for HBV were 3.4/100 pyr (1990–1993: 11.7) and for HCV 38.3/100 pyr (1990–1993: 27.3). HCV seroconversions occurred mostly during the first year after NEP enrolment. Of the 332 cases testing anti-HCV negative at enrolment, 37 were positive for HCV RNA in the same baseline sample (adjusted HCV incidence 31.5/100 pyr). HCV seroconversion during follow-up was significantly associated with mixed injection use of amphetamine and heroin, and a history of incarceration at baseline. In this NEP setting, HIV prevalence and incidence remained low and HBV incidence declined because of vaccination, but transmission of HCV was persistently high. HCV RNA testing in anti-HCV-negative NEP participants led to more accurate identification of timepoints for transmission.

Discussion Only
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For more than two decades, the WHO has promoted needle exchange to prevent sharing of injection equipment and HIV transmission among IDUs. Despite this, many countries have pursued a restrictive policy and in Sweden only two NEPs exist. Furthermore, syringes and needles cannot be purchased legally without a prescription in Sweden.

Because the true efficacy of NEP cannot be demonstrated in randomized controlled trials, continuous evaluation of existing projects is critical. If the prevalence of HIV is very low in an IDU population under investigation, HIV seroconversion is not a reliable marker to detect blood-borne transmission. Like in our 1990–93 cohort, the incidence of HIV remained very low in the 1997–2005 cohort, and no new cases were detected after 1999.

We and others[20,21] have used HBV and HCV as surrogate markers of the potential risk of spreading HIV. It is obvious that HBV immunization can confound the incidence of HBV and affect its usefulness as a surrogate marker. HCV is not effectively transmitted sexually and thus mainly reflects the injection risk, making this virus a more suitable marker of blood transmission.

Following our previous evaluation in 1990–1993, HBV immunization was introduced for unexposed NEP participants, which led to a sharp decline in HBV incidence from 11.7/100 to 3.36/100 pyr.

Our high HCV incidence is alarming (Table 2) and agrees with our previous results and those of others[22–24]. Several reasons may contribute to this phenomenon including the effects of a higher viral load and greater physical virion stability of HCV compared to HIV,[25,26] as well as the much higher background prevalence of HCV among IDUs. Prevention of HCV transmission among IDUs is indeed a challenge, as demonstrated by a meta-analysis of 18 studies,[27] which showed that neither NEPs nor MMT affected the incidence of HCV in IDUs. Researchers in the Netherlands recently found that only a combination of low-threshold NEPs and MMT could reduce HCV transmission among IDUs.[28]

The majority of the participants in the Malmö NEP in 1997–2005 were already infected with HCV at baseline. Furthermore, we found that older age and longer duration of intravenous drug use was associated with HCV infection, and mixed use of heroin and amphetamine and incarceration prior to NEP enrolment were independent risk factors for HCV infection. Our data also show that most cases of HCV seroconversion occurred during the first year after enrolment, which is earlier than reported by Hagan et al. [29]

Retrospective assessment of HCV RNA in frozen key samples from the longitudinal cohort revealed viraemia in 37/332 (12%) of the subjects who were anti-HCV negative at the time of enrolment. In an additional 30 individuals, a viraemic window-phase sample preceded anti-HCV seroconversion. Thus, it is likely that PCR analysis performed prospectively in anti-HCV-negative NEP participants would be a better method for detecting incident cases of HCV infection, permitting earlier and more effective interventions and tracing of transmission chains among such subjects.

After the initial phase of high HCV incidence following enrolment, new HCV infections became rarer in those still susceptible –a phenomenon which could be due both to behavioural and immunological factors.[30]

Our study has limitations. Only NEP participants who were fully identified could be followed, which might have affected the results. However, demographic data reported by identifiable and nonidentifiable subjects were similar. Subjects with only one serum sample available had a higher risk profile compared to those in the longitudinal cohort, but they usually paid single or very few visits to the NEP making it questionable whether they should be regarded as NEP participants. Prospective assessment and monitoring of changes in drug injection risk profile was not consistently documented, nor were sexual risk factors. Furthermore, we were unable to objectively determine exact periods of and reasons for interruptions in NEP participation (e.g. imprisonment, travel or admission to detoxification clinics), and whether such interruptions were associated with changes in the rates of HCV seroconversion.

The effectiveness of a NEP depends on several factors, which, in addition to the number of needles and syringes exchanged,[31] include acceptance and accessibility by the target population, as well as provision of adequate health education and medical services. In the Malmö NEP, limited opening hours and an age requirement of ≥20 years for participation may have been counterproductive, whereas the broad range of services offered probably had the opposite effect. A major advantage of NEPs is the possibility for surveillance of HIV seroepidemiology among IDUs and provide early warning as illustrated by the outbreak of HIV that occurred in 1994 in Vancouver,.[32,33]

In conclusion, the persistently low incidence of HIV in the cohort we studied may be explained by a protective effect of the NEP combined with low background prevalence of HIV. Although NEPs conducted under these circumstances do not affect the incidence of HCV, they do contribute to surveillance and control of HIV transmission in the target population. Molecular testing focusing on participants with anti-HCV-negative samples may offer improved means of case finding.

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