According to the World Health Organization (WHO), injecting illicit drugs is a major risk factor for the acquisition and transmission of HIV, accounting for approximately 5% to 10% of all cases of new HIV infections worldwide.
People who inject drugs (PWIDs) are at higher risk of HIV and other infections because they often share contaminated injecting equipment and, to a lesser extent, engage in unprotected sex. HIV infection results from one of every 125 injections with an HIV-contaminated syringe, one of every 40 to 400 acts of receptive anal intercourse and one of every 2000 to 3000 acts of heterosexual intercourse.
Cohen et al showed that the introduction of early antiretroviral therapy (ART) was associated with a 97% lower risk of infection than delayed introduction. In addition, the researchers found a 90% lower risk of all partner infections and a 69% lower risk in all partner infections during the entire study in the early-ART group. Over the past few years, 30% of new HIV infections outside sub-Saharan Africa have been attributed to injecting illicit drugs. A 2012 study by McArthur et al, found that opiate substitution treatment (OST) – also known as medication-assisted therapy – was associated with a 54% reduction in risk of HIV infection among PWIDs. These findings, said the researchers, could reflect comparatively high levels of motivation to change behaviour and reduce injecting risk behaviour among people who inject drugs who are receiving OST. A new systematic review and meta-analysis, published recently in the journal Clinical Infectious Diseases, set out to investigate the evidence on the effect of OST on ART outcomes among PWID living with HIV. The authors concluded that their findings support the use of OST, and its integration with HIV services, to improve the HIV treatment and care continuum among HIV-infected PWID.
What is OST?
The WHO define OST as the prescription of a drug ‘whose action is similar to that of the drug of dependence, but whose use is less risky’. Agents most commonly used for OST are methadone and buprenorphine, which is administered as a sublingual tablet or film. According to the WHO, OST treatment entails the following:
- Replacement of injected, illicit drugs with non-injected medications
- Use of longer-acting medications to interrupt the cycle of intoxication and withdrawal, an important source of social disruption
- Individually-adjusted, regular dosing to prevent withdrawal and reduce the effect of each opioid dose, which in turn helps to reduce illicit opioid use
- Retention of dependent opioid users in treatment, which facilitates psychosocial interventions
- Treatment delivery in a community setting to allow family and community roles and connections to be maintained
- Enabling opioid dependent drug users to stabilise in health and social terms before addressing the physical dimension of dependence.
Access to ART
According to the authors of the new study, PWIDs often have poor access to HIV treatment. Interventions are needed to improve access and treatment outcomes. The efficacy of OST has been shown in previous studies. The aim of the new systemic and meta- analysis conducted by Low et al, was to quantify the impact of concurrent OST use on the following ART outcomes among PWID. The primary endpoints of the study were:
ART coverage: The proportion of eligible HIV-infected PWID prescribed ART at a fixed point in time, and recruitment is the cumulative proportion who initiated ART during follow-up.
Adherence to ART: The proportion of PWID on ART achieving a defined threshold of ART adherence, whether self-reported or objectively measured.
Viral suppression: The proportion of those on ART with undetectable plasma HIV viral loads, based on the threshold of detection in each study (<500, <400 or <50 copies/mL).
CD4 count response to ART: The median or mean CD4 cell count increase over time on ART. Attrition from ART: The proportion of those on ART who were lost to follow-up or discontinued ART during follow-up, excluding those who died if data was available. Mortality rate on ART: The HIV-related mortality rate during follow-up or, if this was not available, all-cause mortality rate.
The researchers used information available on Medline, PsycInfo, Embase, Global Health, Cochrane, Web of Science, and Social Policy and Practice databases. Data spanned 1996 to 2014 and documented the impact of OST, compared to no OST, on ART outcomes. Meta-analyses were conducted using random-effects modelling, and heterogeneity was assessed using Cochran Q test and I statistics. The researchers included 32 studies, involving 363 27 participants from nine countries.
Endpoints coverage and recruitment onto ART
OST use was associated with a 54% increase in the odds of being on ART with moderate heterogeneity. The researchers found that OST resulted in an 87% increase in ART uptake.
OST was associated with a two-fold increase in adherence, with high between-study heterogeneity. In a subgroup analysis, the effect was higher for studies using self-reported adherence compared with using pharmacy refill.
The use of OST was associated with a 45% increase in the odds of viral suppression. The results were fairly homogeneous.
Increase in CD4 count
The association of OST with increases in CD4 count was difficult to assess because duration of follow-up varied between studies. However, the researchers did find that the increase was substantially larger for those on OST at 12 months in the latter study and another study (65 cells/mm3 versus 14 cells/mm3 and 46 cells/mm3 versus 1 cells/mm3). At 58 months, one study found more patients on OST had achieved immune restoration (gain of >100 cells/mm3) than those not on OST.
Attrition or treatment discontinuation
The average time on ART exceeded 12 months for all five studies reporting it. The pooled estimate found a 23% reduction in the odds of ART discontinuation if on OST with moderate heterogeneity. There was no significant difference in effect by sex, duration of ART, or when studies with inactive PWID were removed.
Six studies were included in the analysis of the impact of OST on mortality while on ART. Only one study presented the impact on HIV-related mortality. There was no evidence for a reduction in all-cause mortality rates among those on OST while on ART compared to those just on ART, although there was substantial heterogeneity.
This systematic review found strong evidence to support the use of OST and its inclusion in routine HIV care for improving the treatment and care continuum among HIV-infected PWID. It supports the need for policy and health system reforms to accelerate the integration of OST and HIV treatment services. The review provides evidence for the multiple potential benefits of OST, and its pivotal importance in a combination approach to harm reduction, concluded the researchers.
Low AJ, Mburu G, Wlton NJ et al. Impact of Opioid Substitution Therapy on Antiretroviral Therapy Outcomes: A Systematic Review and Meta- Analysis. Clin Infect Dis, 2016.
MacArthur GJ, Minozzi S, Martin N. Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis. BMJ, 2012.
Cohen MS, Chen YQ, McCauley M. Antiretroviral Therapy for the Prevention of HIV-1 Transmission. NEJM, 2011.
Gowing LR, Hickman M and Degenhardt L.
Mitigating the risk of HIV infection with opioid substitution treatment. Bulletin of the World Health Organization, 2013.