Attrition during the period from HIV testing to antiretroviral therapy (ART) initiation is high worldwide. We assessed whether same-day HIV testing and ART initiation improves retention and virologic ...suppression.
We conducted an unblinded, randomized trial of standard ART initiation versus same-day HIV testing and ART initiation among eligible adults ≥18 years old with World Health Organization Stage 1 or 2 disease and CD4 count ≤500 cells/mm3. The study was conducted among outpatients at the Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic infections (GHESKIO) Clinic in Port-au-Prince, Haiti. Participants were randomly assigned (1:1) to standard ART initiation or same-day HIV testing and ART initiation. The standard group initiated ART 3 weeks after HIV testing, and the same-day group initiated ART on the day of testing. The primary study endpoint was retention in care 12 months after HIV testing with HIV-1 RNA <50 copies/ml. We assessed the impact of treatment arm with a modified intention-to-treat analysis, using multivariable logistic regression controlling for potential confounders. Between August 2013 and October 2015, 762 participants were enrolled; 59 participants transferred to other clinics during the study period, and were excluded as per protocol, leaving 356 in the standard and 347 in the same-day ART groups. In the standard ART group, 156 (44%) participants were retained in care with 12-month HIV-1 RNA <50 copies, and 184 (52%) had <1,000 copies/ml; 20 participants (6%) died. In the same-day ART group, 184 (53%) participants were retained with HIV-1 RNA <50 copies/ml, and 212 (61%) had <1,000 copies/ml; 10 (3%) participants died. The unadjusted risk ratio (RR) of being retained at 12 months with HIV-1 RNA <50 copies/ml was 1.21 (95% CI: 1.04, 1.38; p = 0.015) for the same-day ART group compared to the standard ART group, and the unadjusted RR for being retained with HIV-1 RNA <1,000 copies was 1.18 (95% CI: 1.04, 1.31; p = 0.012). The main limitation of this study is that it was conducted at a single urban clinic, and the generalizability to other settings is uncertain.
Same-day HIV testing and ART initiation is feasible and beneficial in this setting, as it improves retention in care with virologic suppression among patients with early clinical HIV disease.
This study is registered with ClinicalTrials.gov number NCT01900080.
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.
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.
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.
ClinicalTrials.gov NCT01904994.
The human immunodeficiency virus (HIV) prevention continuum is a framework that illustrates the interconnectedness of each step in the spectrum of prevention services, while emphasizing that all ...steps are needed to decrease HIV acquisition and transmission. This continuum, similar to the HIV care continuum, begins with HIV testing followed by linkage of HIV-uninfected persons to prevention services, retention in such services, and adherence to prevention interventions with repeated HIV testing to monitor for HIV acquisition. To advance the global goal of zero new HIV infections, individuals must receive the entire continuum of prevention services, and no partial credit can be given to achievement of one step in isolation of all steps in the continuum.
Margaret McNairy and colleagues highlight the need for clinical decision tools to help identify HIV patients who would benefit from tailored services to avoid poor outcomes such as death and loss to ...follow-up.
Over 18 million adults have initiated life-saving antiretroviral therapy (ART) in resource-poor settings; however, mortality and lost-to-follow-up rates continue to be high among patients in their ...first year after treatment start. Clinical decision tools are needed to identify patients at high risk for poor outcomes in order to provide individualized risk assessment and intervention. This study aimed to develop and externally validate risk prediction tools that estimate the probability of dying or of being lost to follow-up (LTF) during the year after starting ART.
We used a derivation cohort of 7,031 adults age 15-70 years initiating ART from 2007 to 2013 at 6 clinics in Haiti; 242 (3.5%) had documented death and 1,521 (21.6%) were LTF at 1 year after starting ART. The following routinely collected data were used as predictors in two logistic regression models (one to predict death and another to predict LTF): age, gender, weight, CD4 count, WHO Stage, and diagnosis of tuberculosis (TB). The validation cohort consisted of 1,835 adults initiating ART at a different HIV clinic in Haiti during 2012. We assessed model discrimination by measuring the C-statistic, and measured model calibration by how closely the predicted probabilities approximated actual probabilities of the two outcomes. We derived a nomogram and a point-based risk score from the predictive models.
The model predicting death within the year after starting ART had a C-statistic of 0.75 (95% CI 0.74 to 0.81). There was no evidence for significant overfitting and the predictions were well calibrated. The strongest predictors of 1-year mortality were male gender, low weight, low CD4 count, advanced WHO stage, and the absence of TB. In the validation cohort, the C-statistic was 0.69 (95% CI 0.59 to 0.77). A point-based risk score for death had a C-statistic 0.73 (95% CI 0.69 to 0.76) and categorizes patients as low risk (<2% risk of death), average risk (3-4%), and high-risk (8-10%) and very high-risk (14-19%) with likelihood ratios to be used in settings where the baseline risk is different from our study population. The model predicting LTF did not discriminate well (C-statistic 0.59).
A simple risk-score using routinely collected data can predict 1-year mortality after ART initiation for HIV-positive adults in Haiti. However, predicting lost to follow-up using routinely collected data was not as successful. The next step is to assess whether use of this risk score can identify patients who need tailored services to reduce mortality in resource-poor settings such as Haiti.
Despite significant scale-up of HIV care and treatment across the world, overall effectiveness of HIV programs is severely undermined by attrition of patients across the HIV care continuum, both in ...resource-rich and resource-limited settings. The care continuum has four essential steps: linkage from testing to enrollment in care, determination of antiretroviral therapy (ART) eligibility, ART initiation, and adherence to medications to achieve viral suppression. In order to substantially improve health outcomes for the individual and potentially for prevention of transmission to others, each of the steps of the entire care continuum must be achieved. This will require the adoption of interventions that address the multiplicity of barriers and social contexts faced by individuals and populations across each step, a reconceptualization of services to maximize engagement in care, and ambitious evaluation of program performance using all-or-none measurement.
Adolescents and youth living with HIV have poorer antiretroviral treatment (ART) adherence and viral suppression outcomes than all other age groups. Effective interventions promoting adherence are ...urgently needed. We reviewed and synthesized recent literature on interventions to improve ART adherence among this vulnerable population. We focus on studies conducted in low- and middle-income countries (LMIC) where the adolescent and youth HIV burden is greatest. Articles published between September 2015 and January 2019 were identified through PubMed. Inclusion criteria were: 1 included participants ages 10–24 years; 2 assessed the efficacy of an intervention to improve ART adherence; 3 reported an ART adherence measurement or viral load; 4 conducted in a LMIC. Articles were reviewed for study population characteristics, intervention type, study design, outcomes measured, and intervention effect. Strength of each study’s evidence was evaluated according to an adapted World Health Organization GRADE system. Articles meeting all inclusion criteria except being conducted in an LMIC were reviewed for results and potential transportability to a LMIC setting. Of 108 articles identified, 7 met criteria for inclusion. Three evaluated patient-level interventions and four evaluated health services interventions. Of the patient-level interventions, two were experimental designs and one was a retrospective cohort study. None of these interventions improved ART adherence or viral suppression. Of the four health services interventions, two targeted stable patients and reduced the amount of time spent in the clinic or grouped patients together for bi-monthly meetings, and two targeted patients newly diagnosed with HIV or not yet deemed clinically stable and augmented clinical care with home-based case-management. The two studies targeting stable patients used retrospective cohort designs and found that adolescents and youth were less likely to maintain viral suppression than children or adults. The two studies targeting patients not yet deemed clinically stable included one experimental and one retrospective cohort design and showed improved ART adherence and viral suppression outcomes. ART adherence and viral suppression outcomes remain a major challenge among adolescents and youth. Intensive home-based case management models of care hold promise for improving outcomes in this population and warrant further research.
The evidence in support of use of antiretroviral therapy (ART) for prevention of human immunodeficiency virus (HIV) transmission is encouraging and has stimulated optimism for achieving a dramatic ...change in the trajectory of the HIV epidemic. Yet, there are substantial challenges that, if not addressed, could be the Achilles' heel for this concept. These challenges require strengthening every step of the HIV care continuum, including expansion of HIV testing to reach all those with HIV infection, effective linkage to and retention in care, timely initiation of ART, and high levels of treatment adherence with viral load suppression. Also important is the identification of individuals with acute HIV infection whose contribution to HIV transmission may be substantial. Implementation research is needed to identify strategies that address these challenges and to determine the efficacy of ART for prevention in key populations as well as to evaluate the effectiveness of combination strategies for HIV prevention at the population level.
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.
Link4Health, a cluster-RCT, demonstrated the effectiveness of a combination strategy targeting barriers at various HIV continuum steps on linkage to and retention in care; showing effectiveness in ...achieving linkage to HIV care within 1 month plus retention in care at 12 months after HIV testing for people living with HIV (RR 1.48, 95% CI 1.19-1.96, p = 0.002). In addition to standard of care, Link4Health included: 1) Point-of-care CD4+ count testing; 2) Accelerated ART initiation; 3) Mobile phone appointment reminders; 4) Care and prevention package including commodities and informational materials; and 5) Non-cash financial incentive. Our objective was to evaluate the cost-effectiveness of a scale-up of the Link4Health strategy in Swaziland.
We incorporated the effects and costs of the Link4Health strategy into a computer simulation of the HIV epidemic in Swaziland, comparing a scenario where the strategy was scaled up to a scenario with no implementation. The simulation combined a deterministic compartmental model of HIV transmission with a stochastic microsimulation of HIV progression calibrated to Swaziland epidemiological data. It incorporated downstream health costs potentially saved and infections potentially prevented by improved linkage and treatment adherence. We assessed the incremental cost-effectiveness ratio of Link4Health compared to standard care from a health sector perspective reported in US$2015, a time horizon of 20 years, and a discount rate of 3% in accordance with WHO guidelines.1 Our results suggest that scale-up of the Link4Health strategy would reduce new HIV infections over 20 years by 11,059 infections, a 7% reduction from the projected 169,019 cases and prevent 5,313 deaths, an 11% reduction from the projected 49,582 deaths. Link4Health resulted in an incremental cost per infection prevented of $13,310 and an incremental cost per QALY gained of $3,560/QALY from the health sector perspective.
Using a threshold of <3 x per capita GDP, the Link4Health strategy is likely to be a cost-effective strategy for responding to the HIV epidemic in Swaziland.
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