H*V – can we do better for HIV, HBV and HCV if we all work together?

Editor’s notes: The Sustainable Development Goals (SDGs) signal a major shift in the way that the United Nations and her development partners aim to shape the next decades.  Whereas the Millennium Development Goals reinforced specific programmes for HIV, tuberculosis and malaria, the SDGs call for a more integrated approach to health and well-being and encourage integration and synergy wherever it makes sense.  Hepatitis is one obvious area in which better collaboration and coordination could yield benefits.  Hepatitis B (HBV) and C (HCV) viruses are both more common in some of the populations most affected by HIV.  HCV can now be cured with drugs that derive directly from the HIV portfolio, while some ARVs have a direct effect on HBV.

Rwanda is one of the first countries in sub-Saharan Africa to set up a control programme for viral hepatitis, building on the infrastructure established for HIV. Umutesi and colleagues report on results of screening almost 120 000 people living with HIV who entered care for markers of HBV and HCV.  Around 5000 people (4.3%) were identified with a positive Hepatitis B surface antigen and a similar number (4.6%) were found to have antibodies against HCV.  There was marked variation geographically with a range by district from 2%-11% for HBV, higher in more urban areas and in men.  For HCV the range was from 3%-8% and was higher in more rural areas, and also in men.  This study provides a good platform to estimate numbers of people who might need treatment and to plan the next steps in an integrated programme.

People who inject drugs are particularly severely affected by HCV, and so co-infection with both HIV and HCV is common in areas where both viruses circulate.  Some estimates from Ho Chi Minh City in Viet Nam suggest that more than 40% of people who inject drugs are living with HIV and that essentially all of these people are also co-infected with HCV.  Birger R and colleagues developed a mathematical model to explore the likely impact of interventions aimed at HIV, HCV or broad harm reduction [with methadone maintenance treatment (MMT)] on future mortality and incidence of both infections.  While ART scale up reduces HIV incidence and mortality, it has no effect on HCV.  MMT is effective at reducing incidence of both HIV and HCV (and has morbidity and mortality benefits beyond these viruses).  However, MMT does not help the many people already living with HCV and so has little effect on HCV related mortality. So the model is clear that treatment for HCV needs to be an important part of a combined programme and that we urgently need to find ways to reduce the price of directly acting antivirals if we are to save more Vietnamese lives.

Haldane and colleagues have also focused on this intersection between HIV and substance use services.  They carried out a systematic review to understand the models and implications of integration of service delivery.  The authors expand their typology of integration models considering the point of entry of the client, and the degree to which services are co-located and delivered.  Integration can be considered as “clinical”, “service” or “systems”.  The first two can operate at the micro or meso level meaning that individual staff can deal with both situations, or that staff are trained to provide appropriate referrals.  Systems level integration operates at a macro level and implies that programmes for each service make collaborations and coordinate in ways that may affect staffing, funding and fragmentation of services. Although there are theoretical advantages to coordination and integration (as shown by the mathematical model above), there are few good empirical studies of integrated service delivery reported outside the USA.  The authors considered that most of the intervention studies had a risk of bias in the interpretation of their impact, although all demonstrated positive changes in outcomes.  Furthermore, almost all the studies focussed on integration at the clinic or individual provider level (meso or micro) rather than addressing the larger systemic challenges that we need to consider.  If we are to achieve the ideals laid out in the Sustainable Development Goals, we will need to overcome some of these systemic challenges, particularly for populations that are criminalized and marginalized by many of the public services.

Prevalence of hepatitis B and C infection in persons living with HIV enrolled in care in Rwanda.

Umutesi J, Simmons B, Makuza JD, Dushimiyimana D, Mbituyumuremyi A, Uwimana JM, Ford N, Mills EJ, Nsanzimana S. BMC Infect Dis. 2017 May 2;17(1):315. doi: 10.1186/s12879-017-2422-9.

Background: Hepatitis B (HBV) and C (HCV) are important causes of morbidity and mortality in people living with human immunodeficiency virus (HIV). The burden of these co-infections in sub-Saharan Africa is still unclear. We estimated the prevalence of the hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCVAb) among HIV-infected individuals in Rwanda and identified factors associated with infection.

Methods: Between January 2016 and June 2016, we performed systematic screening for HBsAg and HCVAb among HIV-positive individuals enrolled at public and private HIV facilities across Rwanda. Results were analyzed to determine marker prevalence and variability by demographic factors.

Results: Overall, among 117 258 individuals tested, the prevalence of HBsAg and HCVAb was 4.3% (95% confidence interval [CI] (4.2-4.4) and 4.6% (95% CI 4.5-4.7) respectively; 182 (0.2%) HIV+ individuals were co-infected with HBsAg and HCVAb. Prevalence was higher in males (HBsAg, 5.4% [5.1-5.6] vs. 3.7% [3.5-3.8]; HCVAb, 5.0% [4.8-5.2] vs. 4.4% [4.3-4.6]) and increased with age; HCVAb prevalence was significantly higher in people aged ≥65 years (17.8% [16.4-19.2]). Prevalence varied geographically.

Conclusion: HBV and HCV co-infections are common among HIV-infected individuals in Rwanda. It is important that viral hepatitis prevention and treatment activities are scaled-up to control further transmission and reduce the burden in this population. Particular efforts should be made to conduct targeted screening of males and the older population. Further assessment is required to determine rates of HBV and HCV chronicity among HIV-infected individuals and identify effective strategies to link individuals to care and treatment.

Abstract [1]  Full-text [free] access [2]

The impact of HCV therapy in a high HIV-HCV prevalence population: A modeling study on people who inject drugs in Ho Chi Minh City, Vietnam.

Birger RB, Le T, Kouyos RD, Grenfell BT, Hallett TB. PLoS One. 2017 May 11;12(5):e0177195. doi: 10.1371/journal.pone.0177195. eCollection 2017.

Background: Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) coinfection is a major global health problem especially among people who inject drugs (PWID), with significant clinical implications. Mathematical models have been used to great effect to shape HIV care, but few have been proposed for HIV/HCV.

Methods: We constructed a deterministic compartmental ODE model that incorporated layers for HIV disease progression, HCV disease progression and PWID demography. Antiretroviral therapy (ART) and Methadone Maintenance Therapy (MMT) scale-ups were modeled as from 2016 and projected forward 10 years. HCV treatment roll-out was modeled beginning in 2026, after a variety of MMT scale-up scenarios, and projected forward 10 years.

Results: Our results indicate that scale-up of ART has a major impact on HIV though not on HCV burden. MMT scale-up has an impact on incidence of both infections. HCV treatment roll-out has a measurable impact on reductions of deaths, increasing multifold the mortality reductions afforded by just ART/MMT scale-ups.

Conclusion: HCV treatment roll-out can have major and long-lasting effects on averting PWID deaths on top of those averted by ART/MMT scale-up. Efficient intervention scale-up of HCV alongside HIV interventions is critical in Vietnam.

Abstract [3]  Full-text [free] access [4] 

Integrating HIV and substance use services: a systematic review

Haldane V, Cervero-Liceras F, Chuah FL, Ong SE, Murphy G, Sigfrid L, Watt N, Balabanova D, Hogarth S, Maimaris W, Buse K, Piot P, McKee M, Perel P, Legido-Quigley H. Journal of the International AIDS Society. 2017 May 30;20(1).http://dx.doi.org/10.7448/IAS.20.1.21585.

Introduction: Substance use is an important risk factor for HIV, with both concentrated in certain vulnerable and marginalized populations. Although their management differs, there may be opportunities to integrate services for substance use and HIV. In this paper we systematically review evidence from studies that sought to integrate care for people living with HIV and substance use problems.

Methods: Studies were included if they evaluated service integration for substance use and HIV. We searched multiple databases from inception until October 2015. Articles were screened independently by two reviewers and assessed for risk of bias.

Results and discussion: 11 057 records were identified, with 7616 after removal of duplicates. After screening titles and abstracts, 51 met the inclusion criteria. Integration models were categorized by location (HIV, substance use and other facilities), level of integration from micro (integrated care delivered to individuals) to macro (system level integrations) and degree of integration from least (screening and counselling only) to most (care for HIV, substance use and/or other illnesses at the same facility). Most reported descriptive or cohort studies; in four randomized control trials integrated activities improved patient outcomes. There is potential for integrating services at all facility types, including mobile health services. While services offering screening only can achieve synergies, there are benefits from delivering integrated treatment for HIV and substance use, including ease of referral to other mental health and social services.

Conclusions: Our review used a wide range of databases and conference archives to increase representation of papers from low- and middle-income countries. Limitations include the overrepresentation of studies from the United States, and the descriptive nature of the majority of papers. The evidence reviewed shows that greater integration offers important benefits in both patient and service outcomes but further research and outcome reporting is needed to better understand innovative and holistic care models at the complex intersection of substance use and HIV services.

Abstract [5]  Full-text [free] access [6]

Africa [14], Asia [15], Europe [16], Northern America [17]
Canada [18], India [19], Indonesia [20], Ireland [21], Kenya [22], Rwanda [23], Spain [24], Taiwan [25], Ukraine [26], United Republic of Tanzania [27], United States of America [28], Viet Nam [29]
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