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JAIDS Journal of Acquired Immune Deficiency Syndromes:
Brief Report: Epidemiology and Social Science

HIV Drug Resistance and HIV Transmission Risk Behaviors Among Active Injection Drug Users

Kozal, Michael J MD*; Amico, K Rivet PhD†; Chiarella, Jennifer BS*; Cornman, Deborah PhD†; Fisher, William PhD‡; Fisher, Jeffrey PhD†; Friedland, Gerald MD*

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Author Information

From the *AIDS Program, Section of Infectious Diseases, Yale University School of Medicine and Veterans Administration Connecticut Healthcare System, New Haven, CT; †Center for Health/HIV Intervention and Prevention, University of Connecticut, Storrs, CT; and ‡University of Western Ontario, London, Ontario, Canada.

Received for publication October 18, 2004; accepted February 7, 2005.

J. Fisher is supported by National Institute of Mental Health grant 1R01 MH59473-02, and M. J. Kozal is supported by a Veterans Administration Career Development Award.

Reprints: Michael J. Kozal, Division of Infectious Diseases, Yale University School of Medicine, 135 College Street, Suite 323, New Haven, CT 06510 (e-mail: Michael.Kozal@yale.edu).

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Abstract

HIV+ injection drug users in clinical care may harbor and transmit drug-resistant HIV. We performed a retrospective study of HIV drug resistance and risk behavior among HIV+ injection drug users in care to determine the number of needle-sharing events that involved and the proportion of sharing partners exposed to drug-resistant HIV. Among 180 HIV+ injection drug users, 55 (31%) reported injecting drugs in the previous month, and 22 of these (40%) shared needles and/or works 148 times with 296 partners, of whom 271 (92%) were thought to be HIV or status unknown. Further, 55 (31%) drug users harbored resistant HIV, including 5 (3% of total) who also shared needles and/or works a total of 27 times with 44 partners (18% of all sharing events and 15% of all exposed partners). A small proportion of injection drug users receiving clinical care engage in injection risk behavior and carry resistant HIV; however, because of multiple partners and needle-sharing events, they expose a substantial number of individuals to drug-resistant HIV. Strategies to reduce injection drug use risk behaviors among patients in clinical care are needed to reduce the transmission of sensitive and resistant HIV.

The HIV epidemic remains volatile, with rising rates of drug resistance and continuing transmission risk behavior resulting in significant public health and clinical consquences.1-4 Previous studies have documented that HIV+ injection drug users who are aware of their HIV diagnosis may still share injection drug needles and/or works.5-15 These patients have the potential to harbor and transmit drug-resistant HIV. Most extant studies of injection drug use HIV transmission risk behavior in patients in care have been limited and have not examined the number of needle-sharing events that involve HIV drug-resistant strains, nor have they provided information about the number and perceived HIV serostatus of sharing partners.

To improve our understanding of the characteristics and relation between injection drug risk behavior and drug resistance, we performed a cross-sectional study to determine the prevalence of HIV drug resistance in HIV+ injection drug users receiving clinical care, the frequency with which they shared needles and/or works, and the number and perceived serostatus of needle-sharing partners they exposed to drug-resistant HIV. This information is important in estimating the likelihood of transmission of resistant HIV in this population and providing essential information for prevention strategies.

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METHODS

Participants

Patients who were enrolled in the Options Project study, a longitudinal study of HIV transmission risk in HIV+ patients in clinical care, were recruited from 2 large HIV clinical care sites in Connecticut from 2000 to 2002.15 Inclusion criteria for the Options Project study and the resistance substudy were being at least 18 years old, healthy enough to complete the procedures, and free from obvious signs of dementia. All 497 Options Project-enrolled patients were offered participation in the resistance substudy, which involved agreeing to have a resistance test performed on archived plasma samples. All participants provided written informed consent. The study was approved by the Institutional Review Boards at the University of Connecticut and Hartford Hospital and by the Human Investigations Committee at Yale University.

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Injection Drug Use

Information for this cross-sectional analysis was collected on general demographics, transmission risk categories, and risk behavior specific to injection drug use behavior over the previous month. Participants completed a risk behavior survey via a computer-administered self-interview with audio (ACASI) administered in English or Spanish at a private location within the clinic. The following definitions were used. Active injection drug use was defined as having injected drugs in the previous 1-month period. Injection drug use HIV transmission risk behavior was defined as the sharing of injection needles and equipment without cleaning them first with bleach. A set of assessment items addressed these types of risk behavior. Patients reporting sharing needles or equipment in the last month on any of the assessment items were classified as engaging in risk behavior. High-risk injection drug use HIV transmission behavior was defined as risk behavior with partners believed by the subject to be HIV or of unknown status.

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Laboratory and Resistance Testing

Antiretroviral treatment history, HIV viral loads (VLs), and CD4 cell counts were extracted from patients' medical records. Plasma was collected for VL determinations and genotypic resistance testing within the period covered by the behavioral survey. HIV genotypic resistance tests were performed if the VL was >400 HIV RNA copies/mL. Patients with a nondetectable VL (<400 HIV RNA copies/mL) did not have a resistance test performed and are listed separately in the analyses. Standard DNA sequencing (ABI) was used to detect HIV genotypic resistance using consensus population sequencing of the HIV-1 pol gene.16 A resistance mutation was defined as a major mutation causing resistance using the definitions of the International AIDS Society 2003.17 Neither secondary mutations nor polymorphisms (eg, reverse transcriptase polymorphism V118I) listed for reverse transcriptase or protease inhibitors were included. Resistance patterns, CD4 cell counts, HIV VLs, and behavioral data were merged by coded identifier.

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Data Analysis

HIV+ injection drug use and high-risk behavior across the sample and specific to those with resistance were explored descriptively, and where sufficient group sizes permitted, we assessed the degree to which any of the patient characteristics differed between active injection drug users who shared needles and/or works in the last month versus those who did not share. Patients engaging in needle-sharing behavior were characterized in terms of demography, clinical parameters, HIV drug resistance, and the prevalence and amount of various types of needle-sharing behavior over the preceding 1-month period. All data were analyzed using SPSS, version 11.0.1 (SPSS, Chicago, IL).18

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RESULTS

Patient Characteristics

Four hundred four of the 497 Options Project-enrolled patients (81%) consented and enrolled in the Options Project resistance substudy, 180 (45%) of whom had a history of injection drug use. Of these 180 participants, 63 (35%) were female, 149 (83%) were heterosexual, 15 (8%) were of same-sex orientation, 16 (9%) were bisexual, 70 (39%) were African American, and 56 (31%) were Latino. Most patients (79%) had an annual income less than $10,000, and only 16% had some college education. The demographic, health functioning, and risk values obtained from the current sample did not differ markedly from the values generated from the entire Options Project parent study sample.

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Injection Drug Use Transmission Risk Behavior and HIV Drug Resistance

Of the 180 HIV+ patients with a history of injecting drugs, 55 (31%) were engaged in active drug use (injected drugs in the last month). For the nonactive injection drug users, 13 (7%) reported injecting drugs within the last 2 to 6 months, 18 (10%) injected drugs in the last 6 to 12 months, and 94 (52%) had not injected drugs for >12 months. There were no significant demographic differences between those who were and were not engaged in active drug use. Heroin was the most common drug injected (80%), followed by cocaine (51%), speedball (heroin plus cocaine, 43%), and other drugs (12%). Overall, 18 (33%) of the 55 HIV+ active injection drug users had a nondetectable HIV VL, with the remaining 37 active users having a mean VL of 67,069 HIV RNA copies/mL (median = 19,713 HIV RNA copies/mL; range: 1387-750,000 HIV RNA copies/mL). Thirty-five (64%) were receiving highly active antiretroviral therapy, and 18 (33%) of the 55 active injection drug users had HIV drug resistance.

With respect to injection drug use HIV transmission risk behavior, 22 (40%) of the 55 active injection drug users (40%) reported sharing needles and/or equipment in the previous month. The only significant difference between active injection drug users who did and did not engage in needle sharing was gender. A higher proportion of female active users reported sharing (67%) in comparison to active male injection drug users (30%) (P = 0.013). Those with and without injection drug use HIV transmission behavior were similar across all other demographic characteristics and Short Form 12 (SF12) mental and physical functioning scores. Of the 22 sharers, 16 (73%) had a detectable HIV VL (mean = 41,204 HIV RNA copies/mL, median = 35,318 HIV RNA copies/mL) and only 8 (36%) stated that they were currently taking antiretroviral therapy. Active injection drug users who shared did not differ substantially from those who did not report sharing over the last month with respect to the proportion with nondetectable VLs (27% vs. 36%, respectively; P = not significant).

Five (23%) of the 22 HIV+ active users who shared had drug-resistant HIV. The number of patients engaging in risk, number of risk events, and high-risk events involving resistant variants and number of partners exposed to drug-resistant HIV can be found in Table 1. Briefly, the 22 HIV+ active drug users who were engaged in HIV transmission behavior reported sharing needles and/or works 148 times with 296 with partners, of whom 271 (92%) were believed to be HIV (n = 138) or status unknown (n = 133) and thereby were exposed to high-risk injection drug use transmission behavior. For these 22 sharers, the median number of sharing events in the prior month was 3.5 (range: 1-56 events), exposing a median of 1 partner (range: 1-170 partners). Of the 296 partners, 44 (15%) were exposed by the 5 patients with drug-resistant HIV during 27 sharing events (18% of total events). For these 5 patients with resistance and risk, the median number of sharing events in the prior month was 3 (range: 1-16 events), exposing a median of 2 partners (range: 1-25 partners). Note that the number of partners can be larger than the number of events, given that a patient can have multiple sharing partners during a sharing episode. Seven (32%) of the 22 sharers reported injecting at “shooting galleries” in the last month. With only 5 sharers with resistance and 17 sharers without resistance in the current sample, reliable comparisons of patient characteristics between these 2 groups were not possible.

Table 1
Table 1
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DISCUSSION

This study provides a description of needle-sharing behavior among HIV+ injection drug users who have drug-resistant HIV, the number of needle and/or equipment sharing risk events that involve drug-resistant strains, and the number and perceived HIV serostatus of needle-sharing partners. The results indicate that a small proportion of active injection drug users in clinical care carry resistant HIV and engage in injection drug use HIV transmission risk behavior; however, because of multiple event-related sharing partners, this small number can expose a substantial number of partners during unsafe needle and/or works sharing events.

Continued sharing of injection drug paraphernalia has been shown previously to be common among HIV+ injection drug users, ranging anywhere from 13% to 66%.5,6,13 Our findings are within this range (40%) and extend this observation to HIV+ injection drug users with drug-resistant strains seen in the clinical care setting. Recently, Sethi and colleagues14 evaluated HIV+ injection drug users who were at higher risk for HIV transmission and found that those who engaged in risk had drug-resistant HIV at 14% of the study visits. Our study expands on this important finding by describing the number of injection drug use risk events that involve drug-sensitive and drug-resistant strains and provides information about the number and perceived HIV serostatus of the exposed needle-sharing partners. Taken individually and collectively, this information provides a more complete picture of HIV drug resistance transmission risk in this population. Of particular note is the finding that that the number of partners exposed to sensitive and resistant HIV can be substantially larger than the number of events, given that a patient can have multiple sharing partners during each sharing episode.

Subjects who engage in injection drug use can have considerable variability in the number of times they inject in a month. A large national survey of 10,000 injection drug users demonstrated that there was considerable variation among cities in the mean number of times an injection drug user injected per month, ranging from a high of 253 injections per month (∼8 injections per day) to a low of 19 injections per month (∼1 per day).19 The differences in injection rates were associated with ethnicity, type of drug injected (eg, heroin users ∼101 times per month, speedball users ∼133 times per month), and years of experience.19 In our study, the patients who shared averaged ∼5.8 sharing events per month, which is likely a small fraction of the total injection events that they engaged in per month. Among the 22 patients who reported sharing, 7 (32%) answered that they injected at “shooting galleries” in the last month, a practice that would place them at high risk for having many partners. It should be noted that needle and/or equipment sharing encompasses not only sharing needles but cooker sharing, backloading, front loading, rinse water sharing, filter sharing, and sharing syringe parts to mix drugs with water.19

The risk of transmission of drug-resistant HIV to newly infected patients is of great concern because it can affect treatment responses and clinical outcome.3,4 In addition, there is a risk of possible superinfection with resistant strains among those sharing with partners who may be HIV+.20-22 Thus, the continued HIV transmission risk behavior described in this report poses substantial risk for the HIV+ patient in clinical care as well as his or her partners. Additionally, 10 of the 22 sharers engaged in 262 unprotected sex events with 17 partners in a 3-month period, compounding the risk of transmission.23 It is important to note that although we focused this report on the risk of transmission of resistant HIV, substantial and, indeed, greater risk of transmission of nonresistant HIV was characterized as well in this population.

A limitation of this study is our inability to perform HIV counseling and testing among the exposed partners of the patients to determine the actual rate of transmission of resistant virus. The study design provided strict confidentiality to the patients to facilitate full disclosure of their injection drug use risk behaviors. In addition, although specimens were obtained at the time of the behavioral survey, the analysis of resistance was not performed in real time but in batches well after the reported behavior took place as a designed retrospective analysis to determine the prevalence of drug resistance and not for clinical use. Patients were likely unaware that they were exposing partners to resistant strains. Indeed, only a few patients who shared could report their VL status. In this study, we used strict criteria for an active user (use within previous month) so that we could ensure the HIV drug resistance information obtained was within the window of the sharing events. To obtain detailed behavioral and virologic information on active users is a challenge. Thus, although the sample size of 55 active users with 22 (40%) reporting sharing in the last month may seem small, the results demonstrate that the risk of transmission of drug-resistant strains, even from this small proportion of injection drug users in clinical care, is substantial. Further, our results likely underestimate the overall risk, because the study was cross-sectional, it only evaluated events during a 1-month time frame, and many patients with HIV drug resistance and injection drug use history relapse into drug use over time. Despite these limitations, this study is among the first to provide data linking risk behavior and drug resistance among injection drug users with HIV disease.

In conclusion, a small number of active injection drug users carry drug-resistant HIV and engage in risk behavior; however, because of multiple event-related sharing partners, they expose a substantial number of partners during unsafe needle and/or works sharing events. HIV+ injection drug users in clinical care are accessible for and should receive targeted prevention efforts within the care setting, a strategy now advocated as central to national HIV prevention efforts.1,2,24,25 In addition, treatment of ongoing drug use26 and provision of sterile needles and paraphernalia27 have been shown to decrease HIV transmission among injection drug users and would likely contribute to the reduction of transmission of resistant HIV in this population and their at-risk partners.

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16. Kozal MJ, Shah N, Shen N, et al. Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays. Nat Med. 1996;2:753-759.

17. Johnson VA, Brun-Vézinet B, Clotet B, et al. Drug resistance mutations in HIV-1. Available at: www.IASUSA.org. Accessed July 10, 2003.

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19. Singer M, Himmelgreen D, Dushay R, et al. Variation in drug injection frequency among out-of-treatment drug users in a national sample. Am J Drug Alcohol Abuse. 1998;24:321-341.

20. Altfeld M, Allen TM, Yu XG, et al. HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus. Nature. 2002;420:434-439.

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22. Ramos A, Hu DJ, Nguyen L, et al. Intersubtype human immunodeficiency virus type 1 superinfection following seroconversion to primary infection in two injection drug users. J Virol. 2002;76:7444-7452.

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Keywords:

HIV risk behavior; injection drug use; HIV drug resistance

© 2005 Lippincott Williams & Wilkins, Inc.

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