The distribution of clean syringes to injecting drug users (IDUs) is an effective intervention for reducing syringe sharing and HIV transmission.1-7 Maximizing syringe distribution is a universal principle of effective harm reduction among IDUs.8 International agencies have encouraged the "scaling up" of syringe distribution interventions as a cornerstone of HIV prevention in developing and transitional nations with large IDU populations.8,9 The critical question is what coverage is required to prevent or reverse HIV epidemics among IDUs? If coverage is defined as the number of syringes distributed per injector per injection,10 is it 1 syringe for every injection?11 Or is it the 60% coverage level recommended by United Nation Agencies?12 Unfortunately, the evidence in support of either coverage target is inconclusive, with few, if any, cities achieving the 60% target11,13-15 and other interventions reporting substantial decreases in HIV transmission with much lower coverage.16,17
Few studies have used mathematical modeling to consider the long-term effect of syringe distribution on HIV prevalence,18 and only 1 study has explicitly analyzed the effect of increasing syringe availability on HIV transmission.17 Kaplan's model assumed that IDUs use syringes randomly, with no personal ownership and, under increased syringe distribution, projected an associated reduction in HIV transmission among IDUs.19 However, evidence suggests that, given better access to sterile syringes, IDUs borrow and lend syringes less frequently20-23 and normally share just with close friends.24-26 Indeed, 1 of the main risk factors for sharing, not having a syringe,25,27 decreases with increased access to syringes.2,20,22
In this article, a mathematical model is developed to explore the relationship between an IDU population's endemic HIV prevalence and the coverage of syringe distribution. The model assumes that the frequency of syringe sharing is determined by the shortfall between the supply of syringes and the demand for injecting. The model is run using data from London (United Kingdom) and Svetlogorsk (Belarus).
A mathematical model was developed to estimate the impact of different intervention outcomes on an IDU population's HIV prevalence. To simplify the analysis, the model only simulates HIV transmission through syringe sharing. The coverage of syringe distribution is defined as the average number of syringes obtained by each IDU per year, divided by their average number of injections.
The model considers an IDU population that mixes randomly to form syringe-sharing partnerships. Each IDU receptively shares syringes with m IDUs per unit time with a frequency of n injections per IDU. The model assumes that infected IDUs inject for a duration D, and clean a proportion c of all used syringes, with efficacy e, before reuse. For a susceptible population, the number of IDUs infected by 1 infected IDU is given by the basic reproductive rate R 0 28:
where β is the HIV transmission probability per syringe-sharing act. When the epidemic reaches an endemic state, the HIV prevalence is given by the formula p = 1 − 1/R 0.28
Adjustment for IDUs that Do Not Share Syringes or Have Stable Sharing Networks
If only a proportion (s) of IDUs share syringes, then the endemic IDU HIV prevalence will be reduced by a factor s. In addition, if syringe sharing occurs in small stable networks, the transmission of HIV may be restricted to small segments of the IDU population.29 Indeed, if the IDU HIV prevalence was p 0 when IDUs started sharing in isolated stable groups of size η, then there is a probability [1− (1 − p 0)η] that a particular sharing group will contain at least 1 infected IDU if they were randomly distributed. If the current HIV prevalence was low at this point in time and η is small, then the endemic HIV prevalence p will be reduced to:
In reality, it is unlikely that infected IDUs will be randomly distributed but will be grouped together in specific sharing networks. Therefore, this assumption is likely to overestimate the proportion of IDUs connected to infected IDUs. To overcome this limitation and because of limited data on the size of sharing groups, the parameter η was varied to fit the model to observed HIV prevalence data.
Incorporating Syringe Distribution Coverage
The basic reproductive rate R 0 in Eq. (2) can be approximated by Dmnβ (1 − ec) if n < 20 sharing acts per month. This expression includes the product mn, the number of receptive syringe-sharing events per IDU per unit time. If it is assumed that IDUs normally share syringes when they do not have any,20,22,25 and if improved syringe availability decreases sharing,2,20,22,30,31 then the frequency of sharing can be estimated by the shortfall between the frequency with which an IDU injects (T per unit time) and the product of the number of syringes distributed to the IDU (ε new syringes per unit time) and the number of times each syringe is used by that IDU (δ times before disposal). Note that we assume that injectors' personal reuse of their own syringe is safe. When this expression is substituted into Eq. (2), the following expressions for the required syringe distribution coverage (ε/T) or syringe-sharing rate (mn) needed to obtain a specific endemic HIV prevalence p are obtained:
where S = s(1 − (1 − p 0)η).
Two settings, with contrasting HIV epidemics, are considered in this analysis: London (United Kingdom) and Svetlogorsk (Belarus). These populations were selected because of data availability32-36 and because the majority of syringes used by IDUs came from syringe distribution programs. In addition, coinciding with 1 of the main model assumptions, IDUs in London report having insufficient syringes as the main reason for sharing20,24,26 and that they keep and reuse their syringes to reduce syringe sharing.24 The model parameter values in Table 1 are based on data from these settings.32-39 The IDU population in London has lower levels of reported risk behavior, with half as many IDUs reporting syringe sharing and most reporting that they share with a small number of close friends.40
Table 1 also gives estimates for the HIV transmission probability per syringe-sharing event and the efficacy of syringe cleaning. A sensitivity analysis was undertaken to account for the uncertainty in these parameters.
HIV Prevalence and Syringe Sharing
Figure 1 shows the relationship between endemic HIV prevalence and the average syringe-sharing rate in a homogeneous IDU population where everyone shares syringes and there is no syringe cleaning. The figure suggests that, in such a scenario, the monthly sharing rate has to be less than 4 to reduce the endemic HIV prevalence to less than 10%, and it will be greater than 40% if each IDU shares more than 6 times a month.
Relationship Between HIV Prevalence and Syringe Distribution Coverage
Figure 2 shows a steplike relationship between syringe distribution coverage and the endemic HIV prevalence in each setting. That is, assuming that other factors remain equal, increasing syringe distribution coverage from a low level will have little effect on HIV prevalence until a threshold coverage is reached (15%-20% for Svetlogorsk and 20% for London), after which substantial decreases in HIV prevalence occur. The bold vertical line in each figure shows the current estimated coverage in each setting. The figure suggests what coverage may be required to reduce the IDU HIV prevalence caused by syringe sharing to negligible levels. For example, to reduce the IDU HIV prevalence in London to less than 1%, assuming that syringe reuse remains unchanged, the coverage of syringe distribution has to increase to 27%.
However, increased syringe availability may also lead to a decrease in syringe reuse,41,42 reducing the HIV impact of an increase in syringe distribution. For example, if in Svetlogorsk the frequency of syringe reuse decreases from 3.3 to 2.5 when coverage is increased by 50%, then the endemic HIV prevalence will decrease to 47% instead of reducing to negligible levels if syringe reuse had not changed.
Interestingly, Figure 2 suggests that, given equivalent syringe reuse, the coverage requirements for reducing the HIV prevalence to negligible levels are approximately equal for London and Svetlogorsk. This is due to the expression, 1/(β(1 − ec)DT), in Eq. (3), being small (<0.1), so the coverage required to reduce HIV prevalence to negligible levels is approximately the inverse of the number of times a syringe is used before disposal (1/δ). This corresponds to the coverage being high enough, at the current frequency of syringe reuse, to supply enough syringes to reduce syringe sharing to a sufficiently low level of approximately 2 sharing events per month.
Lastly, despite the similar coverage of syringe distribution in London and Svetlogorsk, there is a large disparity between their current IDU HIV prevalence (Fig. 2). This difference is primarily due to fewer IDUs sharing in London and that they share in small stable groups of 1 to 2 IDUs.24,40
HIV Prevalence and Other Factors
In Figure 3, the impact of other factors on the endemic HIV prevalence is examined. Data from Svetlogorsk are used for Figures 3A to C (the same relationships hold for London), and data from London are used for Figure 3D because the size of sharing networks only impacts on the endemic HIV prevalence in low-HIV prevalence settings.
The duration D that an infected IDU injects for incorporates cessation from injecting and mortality due to all causes. Figure 3A suggests that the impact of increasing the cessation rate is greater when coverage is higher, with the greatest impact achieved when coverage is close to the threshold level. Decreasing the frequency of injection should increase an intervention's effective coverage for the same quantity of syringes distributed (Fig. 3B) and so should also have little impact on the endemic HIV prevalence until a threshold is reached. As for the cessation rate, the impact of decreasing the injection frequency is greater for higher coverage. Figure 3C combines the consistency and efficacy of syringe cleaning into an overall measure of syringe-cleaning effectiveness. The figure suggests that syringe cleaning has significant impact if the syringe coverage is near the threshold (≥25%) or if the overall effectiveness of syringe cleaning is high (>50%). Figure 3D shows that the endemic HIV prevalence in London is sensitive to increases in the size of sharing networks, with very small sharing networks being required to maintain the HIV prevalence at less than 5%, even at high syringe coverage.
Uncertainty in the HIV transmission probability does not substantially affect the model's projections. For example, the required coverage to reduce the HIV prevalence to a negligible level in Svetlogorsk increases from 28% to 29% if the HIV transmission probability is 0.0141, instead of 0.0076, and reduces to 24% if the HIV transmission probability is 0.0029.
The endemic HIV prevalence is also fairly insensitive to changes in the overall effectiveness of syringe cleaning (Fig. 3C). Therefore, despite large uncertainty around the efficacy of syringe cleaning with water (37%-67%),43,44 the actual uncertainty in the overall effectiveness of syringe cleaning is smaller (11%-20% for Svetlogorsk), and Figure 3C shows that this has little impact on our predictions.
We developed a model to explore the relationship between syringe distribution coverage and the endemic HIV prevalence of an IDU population, while incorporating other factors important in the transmission and prevention of HIV. The model assumed that syringe sharing mainly occurs when IDUs have insufficient syringes and that the sharing frequency is determined by the shortfall between the demand and supply for syringes, assuming that each syringe is used a number of times by that IDU. In light of these assumptions, the model suggests that there are critical coverage thresholds for syringe distribution, which have to be reached to substantially reduce the IDU HIV prevalence. However, the results do not support the existence of a universal coverage target, although their usefulness for gauging intervention quality should not be underestimated.
The existence of these coverage thresholds follows on from our predictions that syringe sharing needs to be low (<4 times per IDU per month) before any substantial reduction in HIV prevalence can occur. This is due to the high HIV transmission probability per syringe-sharing event causing the HIV prevalence to be very sensitive to small increases in the monthly syringe-sharing rate and so also the syringe distribution coverage. In contrast, if the syringe-sharing rate increases much more than 4 times per month, then most IDUs connected to an infected IDU become infected, and so any further increase in syringe sharing or decrease in syringe distribution has little effect.
Model Findings and Interpretation
The model suggests that the coverage thresholds mainly depend on the level of "safe" use and reuse of an IDU's own syringes, with the coverage required to reduce HIV prevalence to negligible levels being approximately the inverse of the average frequency with which IDUs safely reuse their own syringes before disposal. Our interpretation of this finding is that syringe reuse can be protective. This finding concurs with advice given by syringe exchanges which recommends that IDUs reuse their own syringe if they run out of clean syringes. Policies or practices that discourage the safe reuse and/or carriage of syringes could reduce the impact of syringe distribution interventions.45-47 However, if syringe reuse is to be promoted, it is important to emphasize that using someone else's syringe is not "safe," and the reuse of one's own syringe can increase the risk of bacterial/wound infections.8,48 Furthermore, some epidemiological studies find an association between HIV and syringe reuse,17,49 probably because syringe reuse can be unsafe or coincide with a tendency to inject more frequently.34,41 These factors need to be considered when devising strategies to promote safer injection by encouraging IDUs to safely reuse their syringes in preference to sharing.
The model suggests that, in general, each IDU needs to share syringes in small stable groups (2-3 people) to limit the spread of HIV, as has occurred in London. Previous studies have also emphasized the importance of network structures50 and specifically small sharing networks in reducing the transmission of HIV among IDUs in New York.50 However, the high HCV incidence in London51 and signs of increasing HIV prevalence 32 imply that syringe sharing may not be as restricted as we thought. If so, there is no room for complacency because, at the current coverage and sharing rate, HIV could easily spread through London's IDU population.
Decreasing the frequency that IDUs inject is also important and should be a focus for health promotion. Equally, patterns of drug taking which increase injecting frequency, such as the rise in cocaine or crack-cocaine injecting,52 may increase HIV transmission and so should be a special target for syringe distribution interventions. Lastly, the results suggest that other factors, such as the rate of cessation of injecting and syringe cleaning, can play an important role in reducing HIV prevalence but only once the syringe distribution coverage is near the critical threshold.
Model Comparisons and Limitations
Although many studies have shown that syringe exchange interventions can decrease syringe sharing or HIV transmission,2 only 1 study from New York has shown that successive increases in syringe availability can lead to parallel decreases in HIV transmission.53 However, although the study also reported that initial increases in syringe distribution have less effect on HIV prevalence, no equivalent trends in syringe sharing or reuse and the size of sharing groups were reported, so limiting direct comparisons with our model. There is an urgent need for further quantitative and qualitative epidemiological studies on the relationship between syringe availability, injecting behavior, and HIV transmission.
Our model projections of the level of syringe sharing required to reduce the HIV prevalence to a low level corroborate with those produced by Murray et al.18 In addition, although not presented here, these results also agree with projections made using a more complex dynamic model, IDU 2.4.54,55 IDU 2.4 also predicted that it would take 10 to 15 years to reach the new endemic HIV prevalence after a reduction in syringe sharing. This highlights the importance of prolonged intervention activity for attaining substantial decreases in IDU HIV prevalence, as highlighted by the long-term impact of harm reduction activities in New York and London.16,53,56,57
Our findings offer a different picture to Kaplan's analysis, which strongly suggested that the impact of the New Haven syringe exchange was due to a reduction in the duration each syringe is used.17 In Kaplan's analysis, IDUs had no ownership of syringes, and so all syringe reuse was potentially unsafe because they could have been used by other IDUs. This assumption agreed with the observation in New Haven but does not reflect other IDU populations, where there is evidence that IDUs retain their syringes to reuse in preference to sharing,24 reduce and restrict syringe sharing when they have access to syringes,20-26 and only use someone else's syringe when they have difficulty obtaining syringes.20,27 Our model reflects these observations and will be relevant in settings where, broadly speaking, these patterns of behavior apply.
The analysis has several limitations and made a number of simplifying assumptions. First, the model assumed that IDUs only share syringes when they do not have their own syringes, although there is evidence that sharing occurs for other social reasons.40,58 Second, the model contains no heterogeneity in IDU risk behavior, and IDUs can only infect their direct sharing partner at each sharing event. Limited sensitivity analysis around these aspects of the model structure (not presented here) suggested that the model's coverage thresholds may be minimum estimates. Third, the model did not include sexual HIV transmission, which sometimes plays a large role in IDU epidemics.59
Despite the model's simplicity, our findings illustrate the importance of discouraging syringe sharing through increased syringe distribution, encouraging the safe reuse of an IDU's own syringes when clean syringes are not available, and supporting interventions that reduce the frequency of injection. In addition, in low HIV prevalence settings, special emphasis should be given to maintaining and encouraging IDUs to inject in small stable groups. Our analysis did not find any evidence for a universal coverage target, but did suggest the existence of coverage thresholds that are related to the frequency of (safe) syringe reuse. In practice, the feasibility of attaining these coverage levels is likely to depend on environmental factors, and optimum coverage targets will therefore be situation dependent.
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