Recent studies indicate that sexual transmission of human immunodeficiency virus type 1 (HIV-1) generally results from productive infection by only one virus, a finding attributable to the mucosal barrier. Surprisingly, a recent study of injectiondrugusers (IDUs) from St. Petersburg, Russia, also found most subjects to be acutely infected by a single virus. Here, we show by single-genome amplification and sequencing in a different IDU cohort that 60% of IDU subjects were infected by more than one virus, including one subject who was acutely infected by at least 16 viruses. Multivariant transmission was more common in IDUs than in hetero- sexuals (60% versus 19%; odds ratio, 6.14; 95% confidence interval [CI], 1.37 to 31.27; P ⴝ 0.008). These findings highlight the diversity in HIV-1 infection risks among different IDU cohorts and the challenges faced by vaccines in protecting against this mode of infection.
In 2004, in the remote desert town of Larkana, Paki- stan experienced its first HIV outbreak . The impli- cated populace was a community of InjectionDrugUsers (IDU), who documented an HIV prevalence approaching an outstanding 27%. Earlier, HIV preva- lence in IDUs was reported by the National AIDS Con- trol Program as bordering around 0.4% in December, 2003. After the Larkana episode, outbreaks were also recorded in other major cities of Pakistan . The chan- ging trend denotes that the country is transitioning from a low prevalence to a concentrated epidemic stage.
The overall objective of this study was to further the understanding of why younger individuals are often more likely to share injectiondrug equipment, and to identify factors that might modify this association. Toward this end we examined data from a cohort of Greater Boston area injectiondrugusers followed during the period in which HCV infection in Massachusetts was observed to increase. Our primary aims were to: (1) de- scribe demographic and drug use practices overall and by age (<25/≥25 years, to correspond to the upper age for which HCV infection was observed to increase in Massachusetts); (2) estimate the association between age and sharing, adjusting for other risk factors of sharing; (3) compare younger (<25 years) and older (≥25 years) in- dividuals on factors present at their most recent sharing injection event; (4) explore whether the association be- tween age and sharing varies between levels of factors indicative of personal stressors or social instability, in- cluding exchange of sex for money, post-traumatic stress disorder (PTSD) symptoms, and whether US born; and (5) summarize the self-reported HCV testing history and the HIV prevalence of injectiondrugusers in the co- hort, overall, by age group, and by sharing status.
Our findings failed to reveal replication differences in any of the other primary cells among viruses sampled during the various phases of disease. Even though, HIV RNA+/Ab- as compared to the chronic envelopes dem- onstrated significantly greater binding to α4β7 high CD8+ T cells, importantly, there was no significant replication difference in the α4β7 high CD4+ T cells. Replication as opposed to binding is likely the more important phenotype that determines a virus’ fitness for establishing a new infection in a naïve individual. Our previous study of recipient transmitter pairs showed that envelope variants circulating in the chronically in- fected sexual partner compared to those present in the newly infected subject had higher replication in CD4+ T cells with high or normal levels of α4β7 levels and with and without MDDCs . In contrast, however, another study showed full length sexually acquired T/F strains had greater MDDC binding and trans infection compared to unrelated chronic infection controls . There are likely a number of reasons we may have failed to observe rep- lication differences in the other primary cells among the 3 groups in our study. Even though we detected some significant phenotypic differences, it is likely that we were statistically underpowered to detect small variations because we only examined 7 subjects in each group. Previous studies using relatively similar number of samples per group (n =6 to 11) showed significant differ- ences in sensitivity to receptor inhibitors and replication kinetics among sexually acquired envelope variants com- pared to the unrelated chronic infection strains or variants circulating in the transmitting partner [5,14,39,57]. Be- cause selection bottleneck is less restrictive during IDU compared to mucosal acquisition, it can be hypothesized that potential differences among the variants at various times post acquisition are likely smaller. Thus, larger sample sizes would be needed to document a significant difference. Although we obtained our samples from one of the largest cohorts of injectiondrugusers , there are still only a limited number of samples from individ- uals sampled prior to HIV-1 seroconversion. We did not seek samples from other cohort of injectiondrugusers because of subject heterogeneity and viral subtype dif- ferences [59,60]. In context to the statistical analyses, it should be noted that we did not adjust for multiple
The WND is available when, where and how addicts need the program, and is flexible in meeting new needs that arise out of the context of addicts' real, and not imagined lives, where illness and the risk of it exist in the life world of the IDU rather than the clinic. The program operates 24 hours a day with a critical coverage during the late night hours in difficult to reach parts of the inner city. It reaches the most vulnerable addicts, immediately, with healthcare (e.g. clean syringes, referrals to detox and treatment, peer support and first aid) as well as entry-level work opportu- nities. The WND recruits active addicts directly from the street to be a part of delivering harm reduction services that draw on their skills and experience. The program builds on the experience and rapport of people with active addictions in order to reach a vulnerable population while maintaining high levels of quality assurance with professional oversight. The centre of gravity for syringe distribution programs needs to shift from politics to epi- demiology. In order for this to be accomplished, needle exchange needs to be replaced by a needle distribution model (unlimited access to syringes). The WND provides a case study for a needle distribution program with the fundamental goal of fitting itself to injectiondrugusers rather than forcing injectiondrugusers to fit to a program. Competing interests
Despite these limitations, these data provide a useful risk profile that can be used to develop tailored prevention programs for these high risk populations. Additional interventions to prevent HIV/HCV transmission should also include increasing the availability of sterile needles through needle exchange programs or pharmacies and expanding drug treatment to prevent or curb injection behaviors. Currently, opiate substitution therapies are not legally available as a form of drug abuse treatment in Paki- stan (T. Zafar, personal communication, 2005); introduc- tion of methadone maintenance and other substitution therapies in Pakistan could help prevent HIV transmission by reducing injection risks among IDUs, as has recently been endorsed by the United Nations and the World Health Organization . Moreover, newly-initiated injectiondrugusers should be targeted for these educa- tion and prevention programs to prevent the further spread of HCV infection.
This study has limitations. As our study sample was generated through street-based recruitment methods, gen- eralizing our findings to other populations of injectiondrugusers requires caution. However, it is noteworthy that the cohort demographics are similar to other local and international studies of drugusers [27-30]. Secondly, as our outcome of interest was willingness to take XR-NTX, actual rates of willingness and successful induction onto XR-NTX will need to be studied in clinical trials in real- world settings. In particular, all elements of the medica- tions’ benefits and side-effect profile could not be fully described in the context of our study. In this regard, as- sessment of specific populations, including HIV-infected individuals, is the subject of ongoing investigation, as can be seen with the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) 055 CHOICES study . Finally, socially desirable responding is a con- cern in studies of marginalized populations . Although interviewers were trained to build trust and rapport with participants, and confidentiality was assured, it is possible we overestimated the percentage of individuals willing to participate as a result of this concern.
Certain limitations must be taken into account when interpreting data from TEDS and UFDS/N-SSATS. Dur- ing our study period, SAMSHA eliminated questions from UFDS about the number of IDUs in treatment programs after 1998. We therefore multiplied the pro- portion of drugusers entering treatment who inject drugs (from TEDS) in each MSA and year by the total number of drugusers in treatment as reported by both UFDS/N-SSATS. Second, these data sets differ in what they count: TEDS counts each admission in a given year, so an individual who enters drug treatment twice or more in a year is counted as two or more indepen- dent cases. In contrast, UFDS/N-SSATS client count numbers are a point-prevalence survey–those in treat- ment on one specific day. It gives a snap-shot of what the substance abuse treatment system looks like on an Table 1 Estimated drug treatment coverage rates (percent in treatment) among injectiondrugusers in 90 large US MSAs, 1993-2002
Premature mortality among injectiondrugusers (IDUs) is higher than in the general population with rates of mor- tality estimated to range between 0.8–3.26/100 person- years [1,2]. Young IDUs are at higher risk for a number of adverse health outcomes, including blood-borne infec- tion, than among young people in the general popula- tion. In a study of new onset injectiondrugusers, mortality rates varied by calendar year, were elevated in comparison to the general population and were estimated to be 3.3 per 100-preson years . In 2002, Roy et al. reported that street youth in Montreal, Quebec, aged 29 years and younger, had a standardized mortality ratio of 11.4 and one of the independent predictors of mortality was injectiondrug use . Younger IDUs represent an important group to examine with respect to mortality due to their higher risk for drug related harms [5,6] and the opportunity to offer new information regarding avenues for prevention among this vulnerable population. Recent studies in the United States and Scotland have found that mortality rates peaked among IDUs in the mid-1990s due to an increase in HIV/AIDS related deaths and have since declined [2,7]. Mortality among IDUs typ- ically result from infectious diseases, overdose and inju- ries [8-10]. Overdose is a leading cause of death among IDUs  and varies between calendar years depending on factors such as purity and quality of drug availability and potentially on the HIV status among individuals [12,13]. Among IDUs in Edinburgh, Scotland deaths due to overdose and suicide were higher among younger IDUs than among older IDUs, with higher proportions of young males than females dying by suicide . In the study of street youth in Montreal, Quebec, overdose deaths and suicide represented the leading causes of pre- mature mortality .
Many Canadian cities are experiencing ongoing infectious disease and overdose epidemics among injectiondrugusers (IDUs). In particular, Human Immunodeficiency Virus (HIV) and hepatitis C Virus (HCV) have become endemic in many settings and bacterial and viral infections, such as endocarditis and cellulitis, have become extremely common among this population. In an effort to reduce these public health concerns and the public order problems associated with public injectiondrug use, in September 2003, Vancouver, Canada opened a pilot medically supervised safer injecting facility (SIF), where IDUs can inject pre-obtained illicit drugs under the supervision of medical staff. The SIF was granted a legal exemption to operate on the condition that its impacts be rigorously evaluated. In order to ensure that the evaluation is appropriately open to scrutiny among the public health community, the present article was prepared to outline the methodology for evaluating the SIF and report on some preliminary observations. The evaluation is primarily structured around a prospective cohort of SIF users, that will examine risk behavior, blood-borne infection transmission, overdose, and health service use. These analyses will be augmented with process data from within the SIF, as well as survey's of local residents and qualitative interviews with users, staff, and key stakeholders, and standardised evaluations of public order changes. Preliminary observations suggest that the site has been successful in attracting IDUs into its programs and in turn helped to reduce public drug use. However, each of the indicators described above is the subject of a rigorous scientific evaluation that is attempting to quantify the overall impacts of the site and identify both benefits and potentially harmful consequences and it will take several years before the SIF's impacts can be appropriately examined.
This cross-sectional study was conducted in HIV-1 infected IDUs and non-drug using controls at Bomu Hospital, a social enterprise facility in Mombasa City, coastal Kenya. Injectiondrugusers were recruited via respondent-driven, snowball and makeshift-outreach sampling methods. In the context of the current study, IDUs comprised of individuals exhibiting injection nee- dle-stick scars and reporting a history of injecting any illicit drug classified by UNODC at least once in the previous month  while non-drugusers were individu- als reporting having never used any of the substances and drugs in the UNODC registry . HIV-1 infection status of consenting IDUs and non-drugusers was con- firmed using Determine ™ (Abbott Laboratories, Tokyo, Japan) and Unigold ™ (Trinity Biotech Plc, Bray, Ireland) in accordance with the Kenya’s guidelines for adult HIV testing . Those yielding positive results on both tests were subsequently recruited into the study. In addition, ART-naive study participants had not been initiated on ART. The ART-experienced study participants were on first-line ART (NRTIs and NNRTIs) consisting of TDF or AZT + 3TC + NVP or EFV . None of the partici- pants were on PIs.
the injection and non-injectiondrugusers. The divorced, widowed or separated individuals form one of the high HIV risk groups in Kenya . However, it is not known whether these individuals acquire the infec- tions pre- and/or post-separation of the marital unions. A number of interacting factors may expose such persons to risk of getting infected. For instance, follow- ing loss of a marital partner and loss of income, an indi- vidual may choose occupations that increase risk of infection. In contrast, individuals reporting never married marital status were fewer in the infected study groups and were less likely to be HIV infected in the non-drugusers. These results are, in part, similar to retrospective demographic and health surveys across Africa showing that married, widowed and divorced women were more likely to be HIV positive compared to never married women . While the underlying reasons for these lower rates remain to be elucidated it is likely that this group is younger, more educated and hence more informed about HIV risk and preventive measures. This assertion is partly supported by previous studies in Tanzania showing that single women with secondary or higher education were less likely to have multiple sexual partners and use condoms than married women with no education [45, 46].
measures [3,4]. Many governments internationally allo- cate the majority of resources to law enforcement strate- gies [5-7]. These tactics include arresting individuals who allegedly use drugs or deal drugs in an effort to reduce drug availability and consumption [8,9]. Despite contin- ued investment in these efforts, there is evidence indicat- ing that this type of enforcement often has little impact on the availability and use of drugs . As well, drug law enforcement has been associated with increases in health- related harms among drugusers [3,11,12]. For example, policing within drug markets has been associated with HIV risk behaviour among injectiondrugusers (IDU) as a result of reductions in uptake of needle exchange and other harm reduction services [3,11,13-15]. Further, drug law enforcement has been associated with various human rights abuses including illegal searches, unlawful detain- ment, and assault [16-18].
Furthermore, person who inject drug (PWID) remain at high risk for both acquisition and transmission of HCV. Findings from Eastern Europe, East Asia and Southeast Asia have reported around 10 million injectiondrugusers being HCV positive. In India, HCVsero-positivity in PWID patients ranges between 20% and 90%. 46 A study conducted amongst PWID users in Amritsar showed 41% drug abuse behaviors such as history of needle, syringe, paraphernalia sharing indicating transmission of HCV infection. 47 Further it was observed that high risk sexual practices (encounter with commercial sex workers and multiple sexual partners) or unprotected sex was seen in 34%-67.1% 18, 47 of PWID user’s which increases the chance of HCV infection. This suggests that indulging in drug abuse behavior and sexual contact with PWID users elevates the spread of HCV infection. Moreover, unsafe injecting practices such as indirect sharing of paraphernalia i.e., drug preparation equipments usually, cookers or spoons, cotton filter and water used for cleaning syringes may result in the spread of virus to family members. 48-50 Thus PWIDs users may also result in intrafamilial transmission of infection.
We also found that 74% of IDU reporting hunger in our cohort were unstably housed. This proportion is ele- vated when compared to findings from a 2006 study within the same cohort, which found that 60% of IDU reported living in a single room occupancy hotel, shel- ter, recovery or transition house, jail, on the street or at no fixed address . The association between hunger and unstable housing suggests that some IDU may not be accessing adequate nutritional services or housing needed to support food security. Over the past 20 years, a conflation of factors have contributed to high levels of homelessness in the Vancouver downtown eastside, where the majority of participants reside, including gov- ernment deinstitutionalization of people suffering men- tal illness and addiction, rapid gentrification of the neighborhood, and insufficient low-cost housing options . As part of the gentrification process, illicit drugusers have also been the subject of ongoing police crackdowns on drug use that have forced them into per- ipheral urban areas . In addition to our data show- ing that IDU are not accessing housing services , recent studies have found that IDU in Vancouver have limited access to essential harm reduction services  and delayed access to HIV clinical services . Taken together, these data suggest the need to scale up multi- ple interventions to improve the health and wellbeing of
Outreach has been an integral part of harm reduction interventions for IDUs worldwide and has been used successfully in reaching IDUs. Programs use ORWs to access, engage and recruit IDUs for services, as IDUs may be reluctant to come into a service facility and may fear interactions with traditional service providers. ORWs are typically salaried workers and are themselves former drugusers or those from the same community as the drugusers so that they can gain the trust of and have credibility with their target population [4-6]. Stud- ies have shown the effectiveness of outreach programs in reducing IDU drug use, risky injection practices, unsafe sexual practices, as well as HIV infection rates [7-9].
Active IDUs were recruited over a 10 month period by peer recruitment, street outreach and from rehabilitation and detoxification facilities. Details of the recruitment patterns  and spatial distribution of participants' place of residence that have been reported previously  dem- onstrated that the sample was broadly distributed throughout the city of St. Petersburg, to some extent over- coming limitations imposed in a non-random sampling if only a single recruitment method had been employed. Individuals were eligible if they injected drugs at least three times per week in the previous month or if on at least three occasions in the previous three months they used injection equipment after another person. Active injection was assessed through detection of recent injec- tion stigmata. Individuals with apparent psychiatric disor- ders were excluded. Initially, individuals 18 years or older were recruited but this was expanded to include those 16 years or older near the end of the recruitment period. Institutional Review Boards (IRBs) at The Biomedical Center and the University of North Carolina approved the study before it started as well as the change in protocol that lowered the age of consent. Additionally, a commu- nity advisory board was developed in St. Petersburg for the purpose of ensuring that participants' rights were pro- tected. Screening was conducted as part of the HIV Preven- tion Trials Network (HPTN) 033 study designed to enroll a cohort of seronegative IDUs for a year's follow-up study preparatory to initiating prevention in St. Petersburg Rus- sia.
The primary outcome of interest in this analysis was a history of compulsory drug detention experience among IDU. We compared IDU who did and did not report a history of compulsory drug detention experience using univariate statistics and multivariate logistic regression. Variables considered included: median age (< 36.5 years vs. ≥ 36.5 years), gender, education level (up to secondary school vs. secondary school or higher), current employ- ment (unemployed vs. employed), current illegal income generation (yes vs. no), average amount of money spent on drugs per day (> 300 vs. ≤ 300 Thai Baht or US$9), heroin injection ever (yes vs. no), methamphetamine injection ever (yes vs. no), methadone injection (i.e., illicit methadone use) ever (yes vs. no), overdosed ever (yes vs. no), use of drugs in combination (yes vs. no), syringe bor- rowing ever (yes vs. no), syringe lending ever (yes vs. no), methadone treatment use ever (yes vs. no), and reporting a history (yes vs. no) of drug planting by police (i.e., police have ever planted illicit drugs on one ’ s person). To examine the bivariate associations between each indepen- dent variable and compulsory treatment experience, we used the Pearson c 2 test. Fisher ’ s exact test was used when one or more of the cells contained values less than or equal to five. We then applied an a priori defined sta- tistical protocol by fitting a multivariate logistic regres- sion model that included all variables that were significantly associated with compulsory drug detention experience at the p ≤ 0.05 level in univariate analyses. All p-values were two-sided. We also investigated the preva- lence of injectiondrug use in the past week among those who reported a history of compulsory drug detention. As well, we compared intensity of recent injectiondrug use ( ≥ daily injecting vs. < daily injecting) among those who did and did not report a history of compulsory drug detention experience using the Pearson c 2 test.