Low dead-space syringes for preventing HIV among people who inject drugs: promise and barriers

Zule, William A.

Current Opinion in HIV & AIDS: July 2012 - Volume 7 - Issue 4 - p 369–375
doi: 10.1097/COH.0b013e328354a276
INJECTING DRUG USE AND HIV: Edited by Lisa Maher and Nick Walsh

Purpose of review: This review examines evidence regarding the differential effects of high dead-space syringes (HDSS) and low dead-space syringes (LDSS) on HIV transmission among people who inject drugs (PWID). It also identifies areas for additional research and examines potential barriers to interventions that promote LDSS.

Recent findings: Results of laboratory experiments and cross-sectional bio-behavioral surveys provide circumstantial evidence that the probability of HIV transmission associated with sharing LDSS is less than the probability of HIV transmission associated with sharing HDSS. Mathematical models suggest that LDSS may prevent injection-related HIV epidemics among PWID.

Summary: Circumstantial evidence suggests that LDSS may substantially reduce HIV transmission among PWID, who share syringes. Additional research that links LDSS to reductions in HIV incidence is needed. Most currently available LDSS are 1 ml or smaller and have fixed needles. These cannot be used by PWID ‘injecting’ larger volumes of fluid and they may be rejected by PWID, who prefer syringes with detachable needles. Nonetheless, LDSS represent a potentially promising intervention that deserves serious consideration.

Correspondence to William A. Zule, Substance Abuse Treatment Evaluations and Interventions Program, RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USA. Tel: +1 919 485 2797; e-mail: zule@rti.org

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Historically most HIV transmission among people who inject drugs (PWID) has been attributed to sharing needles and syringes [1,2], but data on the specific needles and syringes PWID use and share are rarely collected or reported [3]. The limited available data indicate that syringes used by PWID vary in size and design and that some designs retain substantially more blood after use than others [4–7]. The volume of blood in a syringe influences the viral burden (viral burden = viral load × volume of inoculum) in exposures via syringe sharing. This situation is important as viral burden is the underlying concept that explains the heightened risk of HIV transmission during acute infection [8], the protective effect of antiretroviral therapy on transmission [9,10] and the different probabilities of HIV transmission associated with exposures through blood transfusion and needle stick [11,12].

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With the plunger completely depressed, all syringes retain fluid in what has been termed dead-space [13]. High dead-space syringes (HDSS), which usually have detachable needles, retain fluid in the tip of the syringe, the needle hub and the needle itself. In contrast, low dead-space syringes (LDSS) have a needle, which is usually permanently attached, that extends through the tip of the syringe to the base of the syringe barrel. With the plunger fully depressed, LDSS only retain fluid in the needle itself (Fig. 1).

The first LDSS were insulin syringes, which were introduced in 1969 [15]. The reduced dead space allowed diabetics to mix two different types of insulin accurately and it also virtually eliminated insulin waste due to dead space [16,17]. Because of these advantages, pharmacies in many countries gradually phased out the sale of high dead-space insulin syringes and replaced them with low dead-space insulin syringes.

The first published article that called attention to the possibility that differences in syringe design may influence HIV transmission among PWID was published in 1991 [18]. This study compared the effects of 1-ml and 2-ml syringes on the volumes of blood transferred in experiments that simulated accidental needle stick injuries and simulations of needle and syringe sharing by PWID. The study found that compared with 1-ml syringes with fixed needles, 2-ml syringes with detachable needles retained substantially more blood when the plunger was fully depressed. In experiments that simulated needle sharing, 2-ml syringes transferred seven to 10 times more blood than 1-ml syringes [18]. The authors concluded that PWID should be encouraged to use 1-ml syringes.

Although, the authors were interested in the differences between 1-ml and 2-ml syringes, they were actually measuring the effects of syringe design. The potential role of syringe design on HIV risk was first noted in a letter to the editor by Grund and Lern [5] that was published in response to the article by Gaughwin et al.[18]. An article published in 1994 on syringes that were found in prisons in Australia noted that 26% of the syringes had a detachable needle, which was likely to be associated with increased risk compared with sharing syringes with fixed needles [19]. At the time, no more than 10 or 15% of PWID in Australia, who were not incarcerated used syringes with detachable needles (K. Dolan, personal communication, 2012). There are no published articles of the percentages of PWID outside of correctional settings in Australia that were using syringes with detachable needles at the time. A subsequent article by Grund et al.[6] in 1996 on syringe-mediated drug sharing also noted that 1-ml syringes with fixed needles retained less blood and the risk associated with sharing them may be lower than the risk associated with sharing syringes with detachable needles.

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Laboratory experiments that measured dead space in LDSS and HDSS found that 1-ml insulin syringes with permanently attached 28 gauge 0.5-inch long needles retained an average of 2 μl of fluid with the plunger fully depressed [7]. In contrast, 1-ml insulin syringes with detachable 26 gauge 0.5-inch needles and 1-ml tuberculin syringes with detachable 26 gauge 0.375-inch needles retained an average of 86 and 84 μl of fluid, respectively with the plunger fully depressed. These findings were similar to other articles that have noted differences in dead space in insulin syringes with detachable needles and insulin syringes with fixed needles [20,21]. Additional experiments simulated the steps in the injection process of registering (i.e. drawing blood into the syringe to confirm that the needle is in a vein), injection and booting (i.e. drawing additional blood into the syringe to rinse residual drug solution from the dead space). This process was followed by rinsing each syringe twice with 0.5 ml of water each time. In these experiments, HDSS retained an average 1 μl of blood and LDSS retained less than 0.001 μl of blood after rinsing [7]. This amount is slightly less than the volume of blood likely to be transferred if syringes are shared following subcutaneous or intramuscular injection [22], which does not involve intentionally drawing blood into the syringe as is common with intravenous injections. In practical terms this means that at an HIV viral load of 1-million copies per ml the average viral burden (i.e. number of HIV copies in an exposure) in an exposure when an LDSS is shared would be one copy of HIV. In contrast, at a HIV viral load of 1-million copies per ml sharing an HDSS would result in exposure to a viral burden of 1000 copies of HIV. At a viral load of 10 000 copies of HIV per ml, the average HIV viral burden in exposures that involve sharing an HDSS would be 10 copies of HIV, whereas the average HIV viral burden associated with sharing an LDSS would be zero copies of HIV with only one in 100 sharing episodes resulting in exposure to even a single copy of HIV. Several recent studies have found correlations between HIV community viral load and HIV incidence [10,23]. In Vancouver, each log10 increase in HIV community viral load in a cohort of PWID was associated with a 3.32 increase in the hazard ratio for HIV incidence in the cohort [10]. Reasoning by analogy, the effect of PWID in a community using all HDSS vs. LDSS would have the same impact on injection-related HIV transmission as a 3 log10 increase in community viral load. Accordingly, we would expect HIV incidence rates due to syringe sharing to be about 35 times higher (3.323) in areas, where everyone uses HDSS than in areas where everyone uses only LDSS, assuming other risk behaviors are similar.

In laboratory experiments that explored factors (e.g. volume of blood, temperature and so on), which influenced survival of HIV in syringes with detachable needles retained more blood and that HIV survived longer in them [24]. The researchers were only able to culture HIV from LDSS following three rinses with water about 1% of the time. They concluded that sharing HDSS was likely to be more risky than sharing LDSS [25]. A more recent laboratory study examined factors that influenced hepatitis C virus (HCV) survival in syringes. In these experiments, HCV survived for up to 60 days in HDSS, but it only survived up to 1 day in LDSS [26▪▪]. The finding that HCV survives for up to 1 day in LDSS is important as PWID often share syringes within minutes. This situation may partially explain why HCV prevalence is often high even in cities where almost everyone uses only LDSS [3].

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Based on the results of the laboratory studies, it seems plausible that PWID, who share HDSS would be more likely to be infected with HIV than PWID, who only share LDSS. The current review found only four articles based on three studies that included questions on the types of syringes that PWID used and also included HIV or HCV testing [3,27▪,28,29]. Sharing HDSS was linked to increased odds of testing positive for HIV or HCV antibodies in three of the articles [27▪,28,29]. Almost all PWID were using LDSS exclusively at the time of the other study [3] and HIV infection in the sample was too low to produce reliable estimates from multivariable analyses.

One study compared HIV and HCV among PWID in Lithuania and Hungary [27▪]. Almost 10% of PWID in Lithuania tested positive for HIV antibodies whereas 0% (0/215) of PWID in Hungary tested positive. Use of homemade liquid drugs, which has been associated with higher rates of syringe sharing, was more common in Lithuania than in Hungary and in Lithuania. Liquid drugs were almost always injected with HDSS whereas drugs sold in powder form were almost always injected with LDSS. Use of liquid drugs was rare in Hungary and all PWID used only LDSS.

A study in North Carolina in the USA used a propensity score approach [29] to adjust for differences between PWID, who had ever used an HDSS and those who had never used one. For analysis purposes a variable was constructed that classified PWID according to their lifetime behaviors into the following categories: never shared any syringe and never used a HDSS; never shared any type of syringe but used an HDSS; shared an LDSS but never used an HDSS; shared an HDSS but never shared an LDSS and shared both HDSS and LDSS. In multiple logistic regression models that used a propensity score to adjust for differences between people who had ever used an HDSS and those who had never used one, a history of sharing HDSS was associated with increased odds of testing positive for HIV antibodies whereas a history of sharing only LDSS was not. This study used the same variable to examine the relationship between using and sharing HDSS and testing positive for HCV antibodies. In those analyses, there was no association between a history of sharing LDSS and testing positive for HCV antibodies, whereas a history of either using and or sharing HDSS was associated with increased odds of testing positive for HCV antibodies. LDSS seem to provide some protection against HCV infection, but nonetheless HCV prevalence is often high even in places where almost all PWID use only LDSS [3]. This factor may be explained by the fact HCV infectivity is estimated to be 10 times greater the infectivity of HIV and the much higher prevalence of HCV among PWID [12,30,31]. The higher HCV prevalence increases the probability of exposure to HCV and the higher infectivity increases the probability that an exposure will result in infection.

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The findings from the bio-behavioral surveys suggest that PWID, who share only LDSS may be at lower risk of HIV infection than PWID, who share HDSS. Mathematical models can provide insight into the relative impacts of HDSS and LDSS on HIV prevalence among PWID at the population level. Estimates of the probability of HIV transmission through receptive syringe sharing range from 0.0051 to 0.0189 per exposure depending on the genetic subtype (B vs. E) [2,32,33], but these estimates appear to be based on sharing HDSS. A mathematical modeling study estimated the impact on HIV prevalence over time of different percentages of PWID using HDSS and LDSS [14▪▪]. The models used probabilities of HIV transmission of 0.008 and 0.00008 for sharing HDSS and LDSS, respectively. According to the models, injection-related HIV epidemics would not occur among low-risk populations of PWID regardless of whether they were using HDSS or LDSS. However, among populations of PWID that share syringes frequently HIV prevalence would increase rapidly if they were using HDSS. In contrast, injection-related HIV epidemics would not occur and HIV prevalence would decline and fade away even in the presence of high rates of syringe sharing if fewer than 5% of PWID used HDSS. According to the models, use of HDSS by 10% of PWID, in a high-risk population, is sufficient to sustain an epidemic. A limitation of this study was that the models did not include sex risk.

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If the mathematical models are correct, we would expect HIV prevalence among PWID to be low in cities where PWID use only LDSS. Preliminary results from an ecological study have been presented at several recent conferences [34,35]. HIV prevalence was low in cities where PWID used only LDSS, whereas HIV prevalence varied widely in cities where HDSS were used by some or all PWID. These observations are consistent with the results of the mathematical models. Similar ecological data were used as circumstantial evidence that rates of male circumcision may partially explain geographic differences in HIV prevalence in sub-Saharan Africa and other countries [36]. Although ecological data are subject to the ecological fallacy [37], the bio-behavioral surveys that have linked a history sharing HDSS to testing positive for HIV antibodies provide preliminary evidence of a link at the individual level. Comparisons of HIV prevalence among PWID in cities where all PWID use LDSS exclusively and in cities where substantial numbers of PWID use HDSS can serve as natural experiments, if sufficient data are available to rule out alternative explanations [38].

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If LDSS do prevent HIV epidemics among PWID, their importance in preventing HIV among PWID will be dependent upon the willingness of PWID, who use HDSS to switch to LDSS. Prior to the introduction of LDSS in 1969, all PWID used either HDSS or homemade injecting equipment. Use of homemade equipment declined after disposable plastic syringes became widely available in the 1960s. However, in many areas PWID continue to use HDSS almost exclusively [4,39▪▪]. In others, PWID use both HDSS and LDSS [27▪,29] and in some areas PWID use LDSS almost exclusively [3,27▪]. This review only found one published study that examined how and when the transition from HDSS to LDSS occurred [3]. The study examined the transition from HDSS to LDSS that occurred among PWID in San Antonio, Texas, USA between the early 1970s and early 1980s. In San Antonio and other cities in Texas, in the 1960s and early 1970s PWID injected with insulin syringes that they obtained from pharmacies. As pharmacies gradually switched from selling high dead-space insulin syringes to low dead-space insulin syringes PWID were forced to change from HDSS to LDSS [3]. Some PWID were not happy about the change because the LDSS had fixed needles and the barrels were longer and thinner than the barrels of the U-40 and U-80 insulin syringes they had been using, which made it more difficult to manipulate the plunger with one hand. Nonetheless, PWID learned how to use them and later came to prefer them as LDSS virtually eliminated wasted drug solution. This study provides evidence that under certain circumstances, PWID will switch from HDSS to LDSS. There do not appear to be any published articles of the results of interventions to transition PWID from HDSS to LDSS.

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This review found no published recommendations from international organizations regarding the use of LDSS prior to 2000. Since 2000, a report from the World Bank in 2001 on best practices for harm reduction in the Russian Federation included a recommendation for Needle and Syringe programs (NSPs) to encourage PWID to switch from HDSS to LDSS as a means of reducing the risk of HIV transmission [4]. However, the article also cautioned that PWID may be resistant to this change. A WHO guide in 2007 for starting and maintaining needle and syringe programs included recommendations that NSP consider encouraging PWID to switch from HDSS to LDSS, whenever it is feasible [40]. In 2010, a chapter in an edited monograph series from by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) included recommendations for the use of LDSS [41]. In 2011, in response to an HIV outbreak among PWID in Greece, one of the prevention strategies that is being implemented includes promoting the use of LDSS [42].

A rapid assessment, commissioned by the Global Fund to Fight AIDS, Tuberculosis and Malaria and conducted by the Eurasian Harm Reduction Network, published in 2012 examined the types of syringes used by PWID in Eastern Europe and Central Asia [39▪▪]. The review found that HDSS are widely used in the area and that the 1-ml LDSS that are currently available are too small for PWID in the region who inject larger volumes of fluid. The review also noted that many PWID prefer syringes with detachable needles and for this reason, they may be resistant to using LDSS. The article concluded with recommendations for syringe manufacturers to produce LDSS with detachable needles.

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This review found converging evidence from laboratory experiments, mathematical models, ecological studies and bio-behavioral surveys, which suggests that LDSS may substantially reduce the risk of HIV transmission associated with syringe sharing. Despite the strong biological plausibility, all of the evidence to date is circumstantial. There is a critical need for studies that link sharing HDSS and LDSS to differences in HIV incidence in randomized controlled trials in which the main outcome is HIV incidence are the gold standard for testing HIV interventions [43]. However, these trials are very expensive and take years to complete. Before undertaking such a study, it would be essential to develop and pilot test interventions to determine the feasibility of changing the types of syringes use by PWID. Once the feasibility of transitioning PWID from HDSS to LDSS is demonstrated, the next step would be to implement and evaluate an intervention to switch PWID from HDSS to LDSS. This situation would require a cluster randomized trial in which cities or villages are randomized to minimize contamination between intervention conditions. Multisite cluster-randomized trials are even more expensive than simple randomized controlled trials in which individuals are randomized. Such a trial could also be quite difficult to implement as it may not be possible to control all of the sources, where PWID in a cluster obtain syringes.

Although randomized trials will provide the strongest evidence, there is still a need for additional research to assess the relative use of HDSS and LDSS around the world. Almost all HIV risk behaviors among PWID and other groups were initially identified in cross-sectional studies that found associations between behaviors such as syringe sharing and testing positive for HIV antibodies. Accordingly, a great deal could be learned relatively quickly and at low cost by added questions about the use and sharing of HDSS and LDSS to integrated bio-behavioral surveillance surveys that are routinely conducted with PWID in many parts of the world. These surveys could also include questions regarding the acceptability of LDSS. This information is critical for identifying locations, where NSP or policy makers may wish to switch from HDSS to LDSS and use operational research to evaluate changes in HIV incidence among PWID.

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PWID prefer a variety of needle and syringe combinations. PWID that inject liquid drugs and some pharmaceutical drugs often need to inject large volumes (e.g. 5, 10 ml) of fluid [39▪▪]. Some PWID, who inject in deep veins that are usually covered by clothing (e.g. femoral veins) prefer longer thicker needles than PWID, who inject their arms [44]. In addition many PWID prefer syringes with detachable needles [39▪▪]. Most currently available LDSS are 1-ml syringes with needles that are permanently attached, and they are not acceptable to PWID, who inject large volumes of fluid or prefer detachable needles. However, one syringe manufacturer produces 3-ml LDSS and these could be produced in larger sizes if there were a market for them. The issue of detachable needles may be more difficult to resolve. The case study in San Antonio demonstrates that preferences can be changed if LDSS are available in appropriate sizes and HDSS are difficult to obtain [3]. In practice, efforts to transition PWID from HDSS to LDSS with fixed needles may be unsuccessful if PWID have easy access to syringes with detachable needles. Assuming that LDSS do reduce HIV transmission, their full impact on injection-related HIV epidemics among PWID may not be realized unless manufacturers can be persuaded to produce interchangeable low dead-space needles that will fit all standard syringes. If these become available in a range of sizes at prices that are competitive with standard needles, then LDSS could play a major role in reducing HIV transmission among PWID.

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The studies covered in this review provide circumstantial evidence from a wide variety of sources that the probabilities of HIV transmission associated with sharing LDSS are lower than the probabilities of transmission associated with sharing HDSS. Moreover, the studies suggest that these differences in the probability of HIV transmission are large enough that the type of syringe used (i.e. HDSS or LDSS) is an important determinant of whether an injection-related HIV epidemic occurs in a population of PWID that shares syringes. The historical case study in Texas provides evidence that PWID have changed from HDSS to LDSS in some areas. This suggests that it may be possible to develop structural interventions, possibly with a social marketing component, to transition PWID from HDSS to LDSS. LDSS represent a potentially promising intervention that warrants further explorations by harm reduction advocates and researchers.

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I am deeply indebted to all of the numerous collaborators who have provided invaluable contributions to this work over the past 20 years.

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Conflicts of interest

This work was funded by National Institutes of Health Grant Number R03DA026725 from the National Institute on Drug Abuse.

The author has no conflicts of interest to disclose.

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Papers of particular interest, published within the annual period of review, have been highlighted as:

▪ of special interest

▪▪ of outstanding interest

Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 381).

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This article demonstrates the widespread use of HDSS among PWID in Eastern Europe and Central Asia. It also highlights some of the potential barriers to transitioning PWID from HDSS to LDSS.

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HIV; injecting drug users; low dead-space syringes; people who inject drugs

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