Task shifting and sharing for distributing antiretroviral medications to patients living with HIV: Systematic review and meta-analysis Wiysonge, Charles Shey 1,2, Mbeye, Nyanyiwe 1,2, Adetokunboh, Olatunji 1,2, Meg Doherty 3, Negussie, Eyerusalem 3, Kredo, Tamara 2 1 Stellenbosch University, Centre for Evidence-based Health Care, Cape Town, South Africa, 2 South African Medical Research Council, Cochrane South Africa, Cape Town, South Africa, 3 HIV/AIDS department, World Health Organization, Geneva, Switzerland

2 |2 | Outline  Progress and challenges – HIV treatment – Pharmacy health workforce and medication pickup  Systematic review – Objective – Search strategy, study selection, prisma flow, – Findings – Conclusion – Policy and programme implications  Acknowledgements

ICASA |3 | Results Policies adopted in 144 LMIC 6% - treat all 53% - CD4 < 500

ICASA |4 | WHO Consolidated guidelines on the use of ARV drugs for treating and preventing HIV

5 |5 | Pharmacy health workforce in high HIV burden settings: Long waiting time to pick ARV and  Improving efficiency of services and people-centred care are important aspects of chronic HIV care.  Several high HIV burden countries experience shortage of health workforce, including for providing essential pharmacy services.  Long facility waiting time often discourages patients to return back, due to direct or indirect costs of care for patients.  Some high burden countries already implementing alternative models of community ARV distribution by lay providers

6 |6 | Frequency of ARV pickups common practice in selected countries in Southern Africa: The Guy Who Delivers HIV Medicine On His Bicycle: Sizwe Nzima, right, and one of his six employees deliver medicines to patients in a Cape Town neighborhood. Anders Kelto for NPR 3 monthly Monthly monthly monthly Adapted from Eric G presentation. WHO GDG meeting, July 2015.

7 |7 | Systematic Review

8 |8 | Objectives of systematic review  Earlier evidence review on task sharing and shifting for HIV care and ART focused clinical services where nurses and non-clinician physicians provide care in several countries.  The objective of this review is to evaluate the efficacy of sharing and shifting tasks of distributing ART to lay providers in community settings.  This move could support in reducing facility patient load in high burden settings where there is also health workforce shortage.

9 |9 | Method and Searches  March  Any language eligible DATABASES  Cochrane Central Register, PsycINFO, PubMed, Web of Science, WHO Global Health Library  Bibliographies of included studies; other systematic reviews  Consultation of experts in the field CONFERENCES  International AIDS Conferences, IAS pathogenesis, CROI Searc h Core PubMed strategy (modified and adapted as needed for use in the other databases) #4#1 AND #2 AND #3 #3 ((HIV Infections[MeSH] OR HIV[MeSH] OR hiv[tiab] OR hiv-1[tiab] OR hiv-2*[tiab] OR hiv1[tiab] OR hiv2[tiab] OR hiv infect*[tiab] OR human immunodeficiency virus[tiab]OR human immune deficiency virus[tiab] OR human immuno-deficiency virus[tiab] OR human immune-deficiency virus[tiab] OR ((human immun*) AND(deficiency virus[tiab])) OR acquired immunodeficiency syndromes[tiab] OR acquired immune deficiency syndrome[tiab] OR acquired immuno-deficiency syndrome[ tiab] OR acquired immune- deficiency syndrome[ tiab] OR ((acquired immun*) AND (deficiency syndrome[tiab])) or “sexually transmitted diseases, viral”[mh]) OR HIV[tiab] OR HIV/AIDS[tiab] OR HIV- infected[tiab] OR HIV[title] OR HIV/AIDS[title] OR HIV-infected[title]) AND ((HAART[tiab] OR ART[tiab] OR cART[tiab] OR antiretroviral[tiab] OR anti-retroviral[tiab] OR anti- viral[tiab] OR antiviral[tiab] OR "Antiretroviral Therapy, Highly Active"[Mesh])) #2 randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized controlled trials[MeSH] OR random allocation[MeSH] OR double-blind method[MeSH] OR single- blind method[MeSH] OR clinical trial[pt] OR clinical trials[MeSH] OR ("clinical trial"[tw]) OR ((singl*[tw] OR doubl*[tw] OR trebl*[tw] OR tripl*[tw]) AND (mask*[tw] OR blind*[tw])) OR random*[tw] OR research design[mh:noexp] OR prospective studies[MeSH] OR control*[tw] OR volunteer*[tw]) OR observational[tw] OR non-random*[tw] OR nonrandom*[tw] OR before after study[tw] OR time series[tw] OR cohort*[tw] OR cross- section*[tw] OR prospective*[tw] OR retrospective*[tw] OR research design[mh:noexp] OR follow-up studies[MeSH] OR longitud*[tw] OR evaluat*[tiab] OR pre-post[tw] OR (pre-test[tw] AND post-test[tw]) NOT (animals[MeSH] NOT human[MeSH]) #1 (task*[tiab] OR task-shifting[tiab] OR referr*[tiab] OR referral and consultation[mh] OR role*[tiab]) AND (health personnel[mh] OR doctor[tiab] OR doctors[tiab] OR clinician[tiab] OR clinicians[tiab] OR physician[tiab] OR physicians[tiab] OR "healthcare provider"[tiab] OR "healthcare providers"[tiab] OR "health care provider"[tiab] OR "health care providers"[tiab] OR pharmac*[tiab] OR apothecar*[tiab] OR chemist*[tiab] OR dispensar*[tiab])

10 | References from all databases combined in EndNote X6 and duplicates removed One author reviewing titles excluded clearly irrelevant records Two authors working independently applied inclusion criteria in reviewing titles, abstracts and keywords of all records Full texts examined by two authors independently if any doubt TWO studies met inclusion criteria Study selection

11 | Systematic review findings  Two studies with cluster randomized trials met inclusion criteria.  Both studies are from sub-Saharan Africa – Kenya and Uganda.  Both studies enrolled non-pregnant adults living with HIV.

12 | Evidence Summary: Risk of death, lost to follow up or virologic supression Mortality Loss to follow up CI confidence interval; df, degrees of freedom; Moderate quality evidence reveals no risk of death with task shifting as compared to those receiving care in facility (2 cluster randomized studies) Moderate quality evidence reveals no risk of death with task shifting as compared to those receiving care in facility (2 cluster randomized studies) Moderate quality evidence reveals no for risk of lost to follow up with task shifting as compared to compared to those receiving care in facility (2 cluster randomized studies) Moderate quality evidence reveals no for risk of lost to follow up with task shifting as compared to compared to those receiving care in facility (2 cluster randomized studies)

13 | Evidence Summary: Risk of death, lost to follow up or virologic supression Virologic supression Moderate quality evidence reveals no risk of decreased virologic supression with task shifing as compared to those receiving care in facility (2 cluster randomized studies) Moderate quality evidence reveals no risk of decreased virologic supression with task shifing as compared to those receiving care in facility (2 cluster randomized studies) CI confidence interval; df, degrees of freedom;

ICASA | Trained lay providers can distribute ARVs in community settings Trained and supervised lay providers can distribute ARV in community settings (strong, low) Less frequent clinic visits (3-6 months) (strong, moderate) and Less frequent medication pick up visits (3- 6 months) (strong, low) for patients stable on ART can contribute in reducing long queues in facilities and reduce cost of care for patients.

Service Delivery Approaches to Treat All  The HOW: Differentiated care interventions: The Package of Care for stable Less frequent (3-6 months) clinical visits Less frequent (3-6 months) ART refills Community based differentiated care CD4 monitoring stopped where viral load available The Package of Care for advanced disease : Rapid Initiation of ART Cryptococcus antigen screening TB screening following by IPT Screening for toxoplasmosis and cotrimoxazole prophylaxis Intensive follow-up Early Adherence & retention support Advanced Minimal clinical package to reduce M&M Stable Simplified ART delivery- Differentiated Care Models Unstable Adherence vs switch

16 | Conclusions  There is no significant difference in mortality, viral suppression, and loss to follow up between facility and community-based ARV distribution by lay providers in both studies.  In both studies, interventions were implemented as part of broader community and home based HIV treatment programme.  In both trials trained lay providers (i.e. non-health professionals) distributed pre-packaged ARV to patients and were supported, including for back referral of patients when required.  The study population included only non-pregnant adults, who were on ART.

17 | Policy and programmes implications  Spaced clinic and pharmacy pickup visits with community ARV distribution models, linked with health facilities can safely be delivered in similar settings;  Training, supervision and recognition of lay providers is essential for success;  Strengthening patient monitoring and referral systems, including at community level is critical;  Dependable drug supply system to prevent ARV stock outs is essential.

18 | Acknowledgement  World Health Organization  PAPFAR through USAID and the BMGF for funding the systematic review.  The 2015 WHO ARV guidelines development group.