Can the Success of HIV Scale-Up Advance the Global Chronic NCD Agenda?

Noncommunicable diseases (NCD) are the leading causes of death and disability worldwide but have received suboptimal attention and funding from the global health community. Although the first United Nations General Assembly Special Session (UNGASS) for NCD in 2011 aimed to stimulate donor funding and political action, only 1.3% of official development assistance for health was allocated to NCD in 2015, even less than in 2011. In stark contrast, the UNGASS on human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) in 2001 sparked billions of dollars in funding for HIV and enabled millions of HIV-infected individuals to access antiretroviral treatment. Using an existing analytic framework, we compare the global responses to the HIV and NCD epidemics and distill lessons from the HIV response that might be utilized to enhance the global NCD response. These include: 1) further educating and empowering communities and patients to increase demand for NCD services and to hold national governments accountable for establishing and achieving NCD targets; and 2) evidence to support the feasibility and effectiveness of large-scale NCD screening and treatment programs in low-resource settings. We conclude with a case study from Swaziland, a country that is making progress in confronting both HIV and NCD. In September 2011, the United Nations (UN) convened a UN General Assembly Special Session (UNGASS) on noncommunicable diseases (NCD). The event was the second UN High Level Meeting ever held for a health issue, following the successful UNGASS on human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) in 2001. Modeled after its predecessor, the 2011 meeting was intended to catalyze a response to what the World Health Organization (WHO) called an epidemic of “silent killers” that were the leading causes of death and disability worldwide, yet receive little attention from the global health community [1]. Looking back to the prior UNGASS on HIV/AIDS a decade earlier, the NCD meeting aspired to similar goals: rallying multisectoral and cross-national partnerships; stimulating robust donor funding; spurring ambitious targets and commitments on the part of national governments; and catalyzing rapid scale-up of NCD services in resource-limited settings [2]. Advocates highlighted similarities between chronic NCD and HIV/AIDS, including a stark mismatch between the burden of disease and available funding, and the need for programmatic innovation, continuity care, and health systems strengthening 3, 4 and 5. The UNGASS on NCD was successful at producing a Political Declaration to combat NCD [6], and many countries affirmed a commitment to ambitious NCD targets and to implementing evidence-based “best buys” 7 and 8. Yet 5 years later, the global NCD response has languished in what some have called an environment of “malignant neglect” [9]. Despite the fact that NCD account for 37% of disability-adjusted life years in low-income countries [10], only 1.3% of official development assistance for health was allocated to NCD in 2015 [11], a proportion that decreased between 2011 and 2015 [12]. Few resource-limited countries have operational national NCD strategies or adequate NCD services, awareness of and treatment-seeking rates for NCD have not improved [13], and the vast majority of people with cardiovascular disease, diabetes, cancer, and chronic respiratory disease remain undiagnosed and untreated 14 and 15. In contrast, in the years that followed the 2001 UNGASS, global spending on HIV increased by billions of dollars and the number of people initiating antiretroviral treatment (ART) in low- and middle-income countries soared from 400,000 in 2003 to nearly 17 million in 2015 [16]

Low risk of attrition among adults on antiretroviral therapy in the Rwandan national program: a retrospective cohort analysis of 6, 12, and 18 month outcomes

Background: We report levels and determinants of attrition in Rwanda, one of the few African countries with universal ART access. Methods: We analyzed data abstracted from health facility records of a nationally representative sample of adults [≥18 years] who initiated ART 6, 12, and 18 months prior to data collection; and collected facility characteristics with a health facility assessment questionnaire. Weighted proportions and rates of attrition [loss to follow-up or death] were calculated, and patient- and health facility-level factors associated with attrition examined using Cox proportional hazard models. Results: 1678 adults initiated ART 6, 12 and 18 months prior to data collection, with 1508 person-years [PY] on ART. Attrition was 6.8% [95% confidence interval [CI] 6.0-7.8]: 2.9% [2.4-3.5] recorded deaths and 3.9% [3.4-4.5] lost to follow-up. Population attrition rate was 7.5/100PY [6.1-9.3]. Adjusted hazard ratio [aHR] for attrition was 4.2 [3.0-5.7] among adults enrolled from in-patient wards [vs 2.2 [1.6-3.0] from PMTCT, ref: VCT]. Compared to adults who initiated ART 18 months earlier, aHR for adults who initiated ART 12 and 6 months earlier was 1.8 [1.3-2.5] and 1.3 [0.9-1.9] respectively. Male aHR was 1.4 [1.0-1.8]. AHR of adults enrolled at urban health facilities was 1.4 [1.1-1.8, ref: rural health facilities]. AHR for adults with CD4+ ≥200 cells/μL vs <200 cells/μL was 0.8 [0.6-1.0]; and adults attending facilities with performance-based financing since 2004–2006 [vs. 2007–2008] had aHR 0.8 [0.6-0.9]. Conclusions: Attrition was low in the Rwandan national program. The above patient and facility correlates of attrition can be the focus of interventions to sustain high retention

High Levels of Adherence and Viral Suppression in a Nationally Representative Sample of HIV-Infected Adults on Antiretroviral Therapy for 6, 12 and 18 Months in Rwanda

Background: Generalizable data are needed on the magnitude and determinants of adherence and virological suppression among patients on antiretroviral therapy (ART) in Africa. Methods: We conducted a cross-sectional survey with chart abstraction, patient interviews and site assessments in a nationally representative sample of adults on ART for 6, 12 and 18 months at 20 sites in Rwanda. Adherence was assessed using 3- and 30-day patient recall. A systematically selected sub-sample had viral load (VL) measurements. Multivariable logistic regression examined predictors of non-perfect (less than 100%) 30-day adherence and detectable VL (greater than 40 copies/ml). Results: Overall, 1,417 adults were interviewed and 837 had VL measures. Ninety-four percent and 78% reported perfect adherence for the last 3 and 30 days, respectively. Eighty-three percent had undetectable VL. In adjusted models, characteristics independently associated with higher odds of non-perfect 30-day adherence were: being on ART for 18 months (vs. 6 months); younger age; reporting severe (vs. no or few) side effects in the prior 30 days; having no documentation of CD4 cell count at ART initiation (vs. having a CD4 cell count of less than 200 cells/µL); alcohol use; and attending sites which initiated ART services in 2003–2004 and 2005 (vs. 2006–2007); sites with ≥600 (vs. less than 600 patients) on ART; or sites with peer educators. Participation in an association for people living with HIV/AIDS; and receiving care at sites which regularly conduct home-visits were independently associated with lower odds of non-adherence. Higher odds of having a detectable VL were observed among patients at sites with peer educators. Being female; participating in an association for PLWHA; and using a reminder tool were independently associated with lower odds of having detectable VL. Conclusions: High levels of adherence and viral suppression were observed in the Rwandan national ART program, and associated with potentially modifiable factors

Effectiveness of a combination strategy for linkage and retention in adult HIV care in Swaziland: The Link4Health cluster randomized trial

Background: Gaps in the HIV care continuum contribute to poor health outcomes and increase HIV transmission. A combination of interventions targeting multiple steps in the continuum is needed to achieve the full beneficial impact of HIV treatment. Methods and findings: Link4Health, a cluster-randomized controlled trial, evaluated the effectiveness of a combination intervention strategy (CIS) versus the standard of care (SOC) on the primary outcome of linkage to care within 1 month plus retention in care at 12 months after HIV-positive testing. Ten clusters of HIV clinics in Swaziland were randomized 1:1 to CIS versus SOC. The CIS included point-of-care CD4+ testing at the time of an HIV-positive test, accelerated antiretroviral therapy (ART) initiation for treatment-eligible participants, mobile phone appointment reminders, health educational packages, and noncash financial incentives. Secondary outcomes included each component of the primary outcome, mean time to linkage, assessment for ART eligibility, ART initiation and time to ART initiation, viral suppression defined as HIV-1 RNA < 1,000 copies/mL at 12 months after HIV testing among patients on ART ≥6 months, and loss to follow-up and death at 12 months after HIV testing. A total of 2,197 adults aged ≥18 years, newly tested HIV positive, were enrolled from 19 August 2013 to 21 November 2014 (1,096 CIS arm; 1,101 SOC arm) and followed for 12 months. The median participant age was 31 years (IQR 26–39), and 59% were women. In an intention-to-treat analysis, 64% (705/1,096) of participants at the CIS sites achieved the primary outcome versus 43% (477/1,101) at the SOC sites (adjusted relative risk [RR] 1.52, 95% CI 1.19–1.96, p = 0.002). Participants in the CIS arm versus the SOC arm had the following secondary outcomes: linkage to care regardless of retention at 12 months (RR 1.08, 95% CI 0.97–1.21, p = 0.13), mean time to linkage (2.5 days versus 7.5 days, p = 0.189), retention in care at 12 months regardless of time to linkage (RR 1.48, 95% CI 1.18–1.86, p = 0.002), assessment for ART eligibility (RR 1.20, 95% CI 1.07–1.34, p = 0.004), ART initiation (RR 1.16, 95% CI 0.96–1.40, p = 0.12), mean time to ART initiation from time of HIV testing (7 days versus 14 days, p < 0.001), viral suppression among those on ART for ≥6 months (RR 0.97, 95% CI 0.88–1.07, p = 0.55), loss to follow-up at 12 months after HIV testing (RR 0.56, 95% CI 0.40–0.79, p = 0.002), and death (N = 78) within 12 months of HIV testing (RR 0.80, 95% CI 0.46–1.35, p = 0.41). Limitations of this study include a small number of clusters and the inability to evaluate the incremental effectiveness of individual components of the combination strategy. Conclusions: A combination strategy inclusive of 5 evidence-based interventions aimed at multiple steps in the HIV care continuum was associated with significant increase in linkage to care plus 12-month retention. This strategy offers promise of enhanced outcomes for HIV-positive patients

Integrated vs. referred management of CVD risk factors for HIV positive patients on antiretroviral therapy in Swaziland

Cardiovascular disease risk factors (CVDRF) are prevalent in people living with HIV (PLHIV), but the optimal clinical management strategy for patients with both HIV and CVDRF in low resource settings is unknown. In some contexts, care for both HIV and CVDRF is provided in the HIV clinic (“integrated care”), which may be more convenient for patients. In others, PLHIV are referred to specialist clinics for management of their CVDRF (“referred care”) which may lead to higher quality CVDRF management. We compared integrated vs. referred strategies for patients with HIV and CVDRF at an urban health facility in Swaziland, exploring linkage to and retention in CVDRF care, intervention fidelity, and HIV and CVDRF-related health outcomes

Untangling the Relationship Between Antiretroviral Therapy Use and Incident Pregnancy: A Marginal Structural Model Analysis Using Data From 47,313 HIV-Positive Women in East Africa

BACKGROUND: Scale-up of triple-drug antiretroviral therapy (ART) in Africa has transformed the context of childbearing for HIV-positive women and may impact pregnancy incidence in HIV programs. METHODS: Using observational data from 47,313 HIV-positive women enrolled at 26 HIV clinics in Kenya and Uganda between 2001 and 2009, we calculated the crude cumulative incidence of pregnancy for the pre-ART and on-ART periods. The causal effect of ART use on incident pregnancy was assessed using inverse probability weighted marginal structural models, and the relationship was further explored in multivariable Cox models. RESULTS: Crude cumulative pregnancy incidence at 1 year after enrollment/ART initiation was 4.0% and 3.9% during the pre-ART and on-ART periods, respectively. In marginal structural models, ART use was not significantly associated with incident pregnancy [hazard ratio = 1.06; 95% confidence interval (CI): 0.99 to 1.12]. Similarly, in Cox models, there was no significant relationship between ART use and incident pregnancy (cause-specific hazard ratio: 0.98; 95% CI: 0.91 to 1.05), but effect modification was observed. Specifically, women who were pregnant at enrollment and on ART had an increased risk of incident pregnancy compared to those not pregnant at enrollment and not on ART (cause-specific hazard ratio: 1.11; 95% CI: 1.01 to 1.23). CONCLUSIONS: In this large cohort, ART initiation was not associated with incident pregnancy in the general population of women enrolling in HIV care but rather only among those pregnant at enrollment. This finding further highlights the importance of scaling up access to lifelong treatment for pregnant women

Enrollment in HIV Care Two Years after HIV Diagnosis in the Kingdom of Swaziland: An Evaluation of a National Program of New Linkage Procedures

To improve early enrollment in HIV care, the Swaziland Ministry of Health implemented new linkage procedures for persons HIV diagnosed during the Soka Uncobe male circumcision campaign (SOKA, 2011–2012) and the Swaziland HIV Incidence Measurement Survey (SHIMS, 2011). Abstraction of clinical records and telephone interviews of a retrospective cohort of HIV-diagnosed SOKA and SHIMS clients were conducted in 2013–2014 to evaluate compliance with new linkage procedures and enrollment in HIV care at 92 facilities throughout Swaziland. Of 1,105 clients evaluated, within 3, 12, and 24 months of diagnosis, an estimated 14.0%, 24.3%, and 37.0% enrolled in HIV care, respectively, after adjusting for lost to follow-up and non-response. Kaplan-Meier functions indicated lower enrollment probability among clients 14–24 (P = 0.0001) and 25–29 (P = 0.001) years of age compared with clients > 35 years of age. At 69 facilities to which clients were referred for HIV care, compliance with new linkage procedures was low: referral forms were located for less than half (46.8%) of the clients, and few (9.6%) were recorded in the appointment register or called either before (0.3%) or after (4.9%) their appointment. Of over one thousand clients newly HIV diagnosed in Swaziland in 2011 and 2012, few received linkage services in accordance with national procedures and most had not enrolled in HIV care two years after their diagnosis. Our findings are a call to action to improve linkage services and early enrollment in HIV care in Swaziland

The Problem of Late ART Initiation in Sub-Saharan Africa: A Transient Aspect of Scale-up or a Long-term Phenomenon?

Efforts to scale-up HIV care and treatment have been successful at initiating large numbers of patients onto antiretroviral therapy (ART), although persistent challenges remain to optimizing scale-up effectiveness in both resource-rich and resource-limited settings. Among the most important are very high rates of ART initiation in the advanced stages of HIV disease, which in turn drive morbidity, mortality, and onward transmission of HIV. With a focus on sub-Saharan Africa, this review article presents a conceptual framework for a broader discussion of the persistent problem of late ART initiation, including a need for more focus on the upstream precursors (late HIV diagnosis and late enrollment into HIV care) and their determinants. Without additional research and identification of multilevel interventions that successfully promote earlier initiation of ART, the problem of late ART initiation will persist, significantly undermining the long-term impact of HIV care scale-up on reducing mortality and controlling the HIV epidemic

Factors Associated with Late Antiretroviral Therapy Initiation among Adults in Mozambique

Despite recent changes to expand the ART eligibility criteria in sub-Saharan Africa, many patients still initiate ART in the advanced stages of HIV infection, which contributes to increased early mortality rates, poor patient outcomes, and onward transmission. To evaluate individual and clinic-level factors associated with late ART initiation in Mozambique, we conducted a retrospective sex-specific analysis of data from 36,411 adult patients who started ART between January 2005 and June 2009 at 25 HIV clinics in Mozambique. Late ART initiation was defined as CD4 count>100 cells/µL or WHO stage IV. Mixed effects models were used to identify patient- and clinic-level factors associated with late ART initiation.The risk of starting ART late remained persistently high. Efforts are needed to ensure identification and enrollment of patients at earlier stages of HIV disease. Individual and clinic level factors identified may provide clues for upstream structural interventions

The Link4Health study to evaluate the effectiveness of a combination intervention strategy for linkage to and retention in HIV care in Swaziland: protocol for a cluster randomized trial

Background: Gaps in the HIV care continuum contribute to suboptimal individual health outcomes and increased risk of HIV transmission at the population level. Implementation science studies are needed to evaluate clinic-based interventions aimed at improving retention of patients across the continuum. Methods/design: Link4Health uses an unblended cluster site-randomized design to evaluate the effectiveness of a combination intervention strategy (CIS) as compared to standard of care on linkage to and retention in care among HIV-diagnosed adults in Swaziland. The CIS intervention targets a multiplicity of structural, behavioral, and biomedical barriers through five interventions: (1) point-of-care CD4 testing at time of HIV testing, (2) accelerated antiretroviral therapy (ART) initiation for eligible patients, (3) mobile phone appointment reminders, (4) care and prevention packages, and (5) non-cash financial incentives for linkage and retention. The unit of randomization is a network of HIV clinics inclusive of a secondary facility coupled with an affiliated primary facility. Ten study units were randomized based on implementing partner, geographic location, and historic volume of HIV patients. Target enrollment was 2200 individuals, each to be followed for 12 months. Eligibility criteria includes HIV-positive test, age >18 years, willing to receive HIV care at a clinic in the study unit and consent to study procedures. Exclusion criteria included previous HIV care in the past 6 months, planning to leave the community, and current pregnancy. The primary study outcome is linkage within 1 month and retention at 12 months after testing HIV positive. Secondary outcomes include viral load suppression at 12 months, time to ART eligibility and initiation, participant acceptability, and cost-effectiveness. The trial status is that study enrollment is complete and follow-up procedures are ongoing. Discussion: Link4Health evaluates a novel and pragmatic combination intervention strategy to improve linkage to and retention in care among adults with HIV in Swaziland. If the strategy is found to be effective, this study has the potential to inform HIV service delivery in resource-limited settings. Keywords: HIV Linkage Retentio