The case of Scott County: injection drug use and the HIV and hepatitis C virus outbreak

Background

The syndemic of injection drug use (IDU) and HIV infection has been well recognized since the origin of the HIV epidemic. Although transmission in persons who inject drugs (PWID) was documented in 1977 [ ], phylogenetic analysis suggests that the HIV infection was circulating in this population as early as 1970 [ ]. Following rapid spread in this population, it is estimated that at least 100,000 PWID were infected when AIDS was first recognized in 1981, with estimates of HIV infection in PWID ranging from 900,000 to 4.8 million worldwide. At that time, HIV seroprevalence was estimated at 50% in the IDU population in New York City [ ]. Since then, it has been established that IDU is one of the most efficient methods of HIV transmission, behind only blood transfusion and unprotected receptive anal intercourse [ ]. Once introduced, HIV spreads rapidly through a population of PWID, with little genetic variation [ , ]. Incidence rates of up to 10 to 31/100 person-years have been observed in Bangkok [ ], Vancouver [ ], and Tallinn [ ], while other communities have seen HIV prevalence increase up to 50% within 6–24 months, including Kathmandu [ ], Manipur [ ], Kiev [ ], and Rio de Janeiro [ ]. While these outbreaks have occurred in urban and not rural areas, they serve as an example of how rapidly HIV infection can disseminate in these at-risk populations.

Factors that have been associated with the rapid spread of HIV in communities include limited knowledge of risk, limited access to sterile injection equipment, and large, frequently changing networks of injection partners [ ]. While not all factors must be present for an HIV outbreak to occur in PWID, a number of these (frequently modifiable) factors are typically present [ ].

Outbreak

In December 2014, a physician in Austin, Indiana, identified two new diagnoses of HIV infection, shortly followed by a third case. These were quickly followed by 8 others and by the end of March 2015, 68 new cases of HIV infection had been identified [ ]. By November 1, 2015, 181 cases had been diagnosed [ ], with 205 cases by September 2016 [ ] and 215 by March 2, 2017 [ ] ( Fig. 2.1 ).

Subsequent phylogenetic analysis revealed a sequence homology of over 99.5%, confirming a single common source of the outbreak while laboratory and clinical evaluation of most newly diagnosed patients was consistent with infection within 2–6 months of diagnosis [ ]. Further phylodynamic analysis indicated an initial introduction into a tight network of PWID via high-risk sexual contact at some point in 2011 and rapid expansion in mid-2014, with most transmission events having occurred by early 2015 before the declaration of a public health emergency on March 26, 2015 [ ] ( Fig. 2.2 ).

The nature of the opioid itself and the associated injection practices contributed significantly to the rapid spread of HIV. In Austin, a sustained-release formulation of oxymorphone (Opana ER) was used. Oxymorphone is a semisynthetic μ-opioid agonist first approved in the United States in 1959. It was initially available only in injectable and rectal forms but was subsequently made available in both immediate- and extended-release oral formulations [ , ]. The injectable formulation has an onset of action within 5 min, has a half-life of 3–6 h, and is approximately 30-fold more potent than oral morphine [ , ]. The extended-release formulation utilized a novel proprietary drug matrix (TIMERx) that provided a different pharmacokinetic profile than either the injectable or the immediate-release oral formulation. This matrix consisted of a xanthan and locust bean gum–derived hydrophilic polymer that resulted in the gradual degradation of the matrix and release of the active medication [ ]. This formulation was marketed as “abuse deterrent” and was intended to prevent immediate release of all active drugs following crushing and insufflation [ ]. Owing to community perceptions of this medication being “safer” (i.e., a pharmaceutical product manufactured under sterile conditions without adulteration), it rapidly became the preferred agent for nonprescription use in this community [ ]. This required complex processing of the extended-release tablets to obtain oxymorphone for injection, consisting of “browning” or slow heating of the tablet, followed by solubilization with water and finally, injection. As the resulting solution was poorly soluble in water, the total volume required multiple “takes” (drawing up and injecting) per episode. Frequently, users described using two to three “flushes” to obtain all the drug present in a single quarter tablet. Furthermore, owing to the high cost of the drug, a single delayed-release tablet was shared among multiple—frequently between two and four—injection partners [ ], and given the high potency and short half-life of the injected oxymorphone, withdrawal symptoms were faster and more severe, requiring between three and seven injection episodes per day. This combination of multiple users sharing a single tablet, multiple injections required per episode, short high and rapid, intense withdrawal combined to provide an ideal situation that promoted frequent nonsterile injection practices associated with the transmission of hepatitis C virus (HCV) and HIV infections [ ]. HIV subsequently spread rapidly in this population and was further amplified among those who participated in transactional sexual activity (up to 25% of the HIV-infected women in this outbreak) [ , ]. This finding of high levels of transactional sexual activity and IDU has also occurred in other populations with high incident rates of HIV and HCV infection [ ]. This level of transactional sexual activity, combined with the frequent injections and close network of PWID mentioned earlier, further enhanced the spread of HIV infection in this community.

An outbreak similar to Scott County occurred in London, Ontario. This outbreak was strongly associated with the illicit injection of sustained-release hydromorphone, with the microcrystalline cellulose present in the sustained-release tablets serving to prolong the viability of HIV present [ ]. As in the Scott County experience, the sustained-release hydromorphone preparation was poorly soluble in aqueous solution, so the preparation for injection also required multiple steps, in this case including crushing, heating, suspending in water, and passing through a cotton filter to remove particulate matter, and owing to the high volume required for solubilization, multiple injections were frequently shared [ , ].