With the ambitious goal to end the AIDS epidemic by 2030, UNAIDS has set clear benchmarks with the 90–90–90 strategy for 2020. Reaching the second 90 requires that 90% of people living with HIV (PLWH) know their status, and 90% engage in antiretroviral therapy (ART) . Global estimates report that 79% of PLWH know their status and 78% are on treatment, with 86% reaching viral suppression . Although progress towards global targets has steadily increased, gaps in the cascade of care remain, including approximately 8.1 million PLWH who are unaware of their status and thus not accessing ART . In addition to extending testing programs, expansion of subsequent linkage to HIV care and treatment is needed to achieve the 2020 benchmarks [3▪].
Strategies for linkage to care for HIV and initiation of ART are inherently related to the method of testing, as testing is a first step in the HIV care cascade and often serves as the initial link to the formal healthcare system. It is increasingly important to understand differentiated service delivery strategies and outcomes for linkage from different testing modalities as the endorsement of universal test and treat (UTT) has seen global expansion, whereby all PLWH are initiated on ART regardless of disease stage . UTT gradually becoming standard of care has led to increased demand for linkage to ART, including for PLWH who are asymptomatic [5,6▪,7,8▪▪,9].
Moreover, as the second step of the 90–90–90 cascade, initiation of ART is a pivotal determinant of the final 90, successful maintenance of ART leading to viral suppression. With UTT and increased engagement with HIV care for those PLWH, prevention of infection also increases with the proportion of PLWH with undetectable viral loads, a strategy known as ‘Treatment as Prevention’ [10–12]. A US-based mathematical model estimates that the majority of HIV transmissions occur among people who have known HIV status but are not in care . To increase uptake of HIV testing and linkage, leading to subsequent viral suppression, rapid and enhanced efforts are needed to improve linkage to care.
This review provides an overview of recently published, novel interventions for increasing linkage to HIV care grouped under the categories of: clinic-based linkage, linkage from community-based settings, and linkage from self-testing and index testing (assisted partner notification). A summary of these studies is provided in Table 1. We provide insight into the contributions of these studies to the literature on linkage to HIV care and conclude with commentary on the opportunities for further research and development of HIV care linkage programs. Selected on-going studies of linkage, registered with ClinicalTrials.gov, are presented in Table 2.
HIV testing and linkage to ART within traditional clinical settings serves as the bedrock for many HIV care programs. Clinic-based testing often engages symptomatic patients with lower CD4 counts and a more urgent need to evaluate for opportunistic infections and promptly start ART . Additionally, clinic-based testing often leads to better linkage outcomes, as compared with community-based testing, because testing and service provision may be in closer proximity [14,15]. However, engagement in HIV care programs in clinical settings are subject to multiple formidable and interacting barriers, including stigma and transportation costs, which may result in delays or deferral of testing and linkage . Furthermore, key populations, such as people who inject drugs (PWID), transgender persons, or females who engage in sex-work (FSWs), may experience additional situational stigma and increased barriers preventing linkage to care [17–19]. Novel strategies to address some of these barriers modify access to HIV care, from testing to linkage, within clinic settings.
Halperin et al. assessed care outcomes for an immediate ART program in a clinic in the Southern United States where more than 50% of patients were participating in Medicaid (public health insurance safety net). Rapid ART was provided in two groups: patients who were newly diagnosed, linked immediately, and offered same-day ART and those who were ART-naïve, diagnosed greater than 72 h (range, 4 days to 25 years), linked on the day of contact and offered same-day ART. Among the newly diagnosed, 100% were started on immediate ART, 99% achieved viral suppression, and 92% were retained in care. Among PLWH that were diagnosed previously, 99% initiated same-day ART, 94% achieved viral suppression, and 80% were retained in care. Those in the previously diagnosed group experienced higher rates of mental health diagnoses (20 vs. 33%, P = 0.039), perhaps indicative of competing needs. This intervention is notable for its success in maintaining patients in the cascade of care with an immediate initiation of ART and little attrition.
Case management, often facilitated by peer-counselors, endorses HIV referral and linkage to care as an ongoing process rather than a one-time event. A study of case management performed in St. Petersburg, Russia, used a modified ARTAS (Antiretroviral Treatment Access Study) case management intervention , tailored to the Russian context, to address societal and structural barriers to linkage for HIV care for PWID in an urban center [22▪]. These barriers included stigmatization of drug use and resource siloes for addiction and infectious diseases treatment services. The LINC intervention (Linking Infectious and Narcology Care) integrated a peer-led, strengths-based case management strategy with infectious disease and narcology care. Although the LINC intervention group had higher rates of linkage at 6 months compared with standard of care (51 vs. 31%, P < 0.001), the difference was not maintained at 12 months. A second LINC study underway is offering concurrent pharmacologic treatment for opioid use disorder (ClinicalTrials.gov #NCT03290391). These studies highlight the importance of transcending the separation between HIV care and other medical services and the need to improve durability of linkage and retention in these integrated programs.
In response to low uptake of HIV testing and linkage services, Solomon et al.[23▪▪] investigated the use of integrated care centers for key populations in 11 cities in India. Six care centers were created within opioid agonist treatment centers and five MSM centers within government-sponsored health services. After implementation, recent HIV testing was 31% higher at integrated care centers, when compared with usual care sites (nonsignificant). At the individual level, participants at integrated care centers were more likely to report recent testing for HIV [adjusted prevalence ratio (PR) 3.46, 95% confidence interval (CI) 2.94–4.06] and receiving ART (adjusted PR 1.25, 95% CI 2.94–4.06), and significantly higher rates of prevention strategies (needle and syringe exchange 2.27, 1.76–2.94; opioid agonist treatment 4.25, 3.17–5.69; STI evaluation at MSM sites 3.71, 2.05–6.73; partner testing 1.61, 1.36–1.91). Although the research design did not have the population effects expected by the investigators, 94% of PWID and 99% of MSM who received care at an integrated center either strongly agreed or agreed with the statement ‘I am satisfied with the services I received today’.
HIV care integration with reproductive health services is a strategy for preventing vertical and horizontal transmission of HIV in cases of serodiscordant couples with pregnancy intentions. A study in Johannesburg, South Africa, demonstrated the use of safer conception care integrated with ART and PrEP provision for couples with at least one partner living with HIV . ART was initiated in 91% (73/80) of the HIV-positive participants not on ART and PrEP was initiated by about one-quarter of HIV-negative participants (28%, 28/101). The comprehensive intervention package was adjusted to individual participant's needs. Adoption of the services was high, and there were no incidents of onward transmission to either partners or infants.
Case management and integration of care with other health services improves HIV care for PLWH by reducing barriers to care. Modifications to the clinical setting, such as those described above, addresses the demonstrated need to make the linkage process more patient-centered.
Testing services offered in homes or within community settings offer many benefits with regard to privacy and convenience and are acceptable in many settings [14,15,19]. However, testing outside of traditional clinic facilities presents the formidable challenge of providing access to care to PLWH, most often necessitating a link to formal health systems [8▪▪,16]. Even large trials with wide access to treatment and implementation of referral for linkage strategies have yielded delays in ART uptake [8▪▪,25,26].
An intervention in Eswatini offering the CDC recommended package of peer-delivered linkage services saw similar success in linkage to ART among patients tested in community versus facility settings (overall time periods, 87 vs. 86%, respectively). The intervention included peer-supported case management, escort, and reimbursement for transportation costs, treatment navigation, appointment reminders, and other psychosocial support. Among those joining the study during the period of Test and Start, 97% of participants diagnosed in a community setting enrolled in HIV care within 90 days of program consent . The findings support the acceptability of the CDC recommended package, and the utility in helping programs reach near universal linkage to HIV care and initiation of ART.
Ayieko et al.[8▪▪] assessed linkage outcomes of a patient-centered strategy as part of the SEARCH study, a community-based test-and-treat trial in Kenya and Uganda. The strategy included personal introduction to clinic staff member at time of positive test, access to a resource ‘hotline’, one-time reimbursement for transportation to clinic, appointment reminders, and telephone and in-person tracing if the first appointment was missed. Nearly three-quarters of the participants were linked after 1 year, and 50% linked within the accelerated linkage window of 7 days. Those who tested through home-based testing were about 25% less likely to link within a month, as compared with those tested through multidisease community health campaigns. Of note, those who previously knew their HIV status (427, 21%) were slower to link to care.
A randomized trial in Lesotho (CASCADE) sought to understand the effect of offering same-day ART vs. referral to a clinic after positive home-based HIV test. Among those provided same-day ART, 69% were linked to care at 90 days compared with 43% in the standard-of-care health facility referral group. The differences in outcomes remained statistically significant for viral suppression 11–14 months after enrollment with 50% in the same-day ART and 34% in standard-of-care group . The authors posit that immediate linkage following home-based testing may be a more scalable strategy than multicomponent facility-based interventions for endemic areas.
An intervention for community-based ART delivery was demonstrated for FSW in Tanzania, in a setting of high-disease prevalence (27% compared with 6.5% among general population adult women), high levels of stigma, and low levels of ART access . Participants in the intervention arm received immediate adherence counseling and 1-month supply of ART with ongoing ART delivery at a community location of their choosing, the comparison received facility-based ART services . Participants in the intervention arm were more likely to have initiated ART (100 vs. 72%, P = 0.04), to be taking ART at 6 months (100 vs. 95%, P < 0.001), and less likely to have stopped taking ART for more than 30 days continuously (0.9 vs. 5.7%, P = 0.008). The FSWs receiving community-based ART were also less likely to report high internalized HIV stigma. This intervention addressed social and structural barriers by allowing immediate ART initiation and ongoing ART provision in community venues, supporting community-based ART not only for those deemed stable at the facility-level (as per current Tanzanian guidelines) but also for those initiating treatment.
The TransLife Care (TLC) project addressed structural barriers to engagement in HIV care by providing housing, employment, legal, and out-reach based health services with HIV case management for transgender women, who experience a disproportionate burden of HIV in the United States . The services were delivered by a transgender individual when possible. Over 24 months of follow-up, receiving any element from the package of services was associated with engagement in care, more visits, retention in care, and viral load testing. However, the authors also report that engagement with care and retention declined with time, and there was no significant association between receiving the intervention and viral suppression. Regardless, this notable intervention yielded improvement in linkage by directly addressing determinants of access to HIV care in transgender people in the United States.
The convenience offered by community-based and self-testing necessitates innovative solutions to linkage to the formal healthcare system. However, programs with either direct or indirect linkage support can help reduce barriers experienced by PLWH.
LINKAGE FROM SELF AND INDEX TESTING
HIV self-testing (HIVST) is increasingly recognized as a novel method for engagement in HIV treatment and prevention programs, particularly for members of key populations, as it directly addresses barriers related to stigma and discrimination in health facilities and at community venues [15,29]. HIVST expanded in Africa through policy and market changes catalyzed by the STAR (Self-Testing Africa) Initiative and endorsed by WHO in 2016. With the expansion of HIVST in six southern African countries through the STAR Initiative, multiple concerns were raised with regards to linkage to confirmatory testing and ART following HIVST . Documentation of linkage is important as many studies show that expanded access to diagnosis through HIVST does not necessarily increase ART uptake [31,32▪▪,33].
In STAR, preferences for linkage to HIV care services following a reactive self-test were explored through discrete choice experiments embedded in a household survey . The most important barriers cited to linkage after HIVST were costs associated with a clinic-based confirmatory testing and long wait times in clinics; facilitators were noted as follow-up phone call and follow-up care offered in the home of a counselor. The findings indicate a need for additional follow-up after a positive HIVST and creative strategies to reduce barriers to promote confirmatory testing and additional follow-up after positive HIVST.
Choko et al. evaluated the role of financial incentives after self-testing for male partners of antenatal clinic (ANC) attendees. This is a particularly important population for improved HIV testing and linkage, given the low rates of testing and linkage in men and the risk of vertical transmission during pregnancy [32▪▪]. The five-arm trial provided a standard-of-care arm and four modified interventions to incentivize linkage including: receipt of two HIVST kits, two HIVST kits and $3, two HIVST kits and $10, two HIVST kits and entry into a lottery, and 2 HIVST kits and a phone call reminder [32▪▪]. The primary outcome was the proportion of male partners who tested for HIV and linked to care or prevention within 28 days, with referral for ART or circumcision, accordingly. Seventeen percent reported testing in the standard-of-care arm whereas men in all testing arms had higher testing rates, ranging from 87 to 95% (P < 0.001 for all five arms). Meeting the primary linkage endpoint was significantly associated with financial incentive arms [HIVST + $3 geometric mean 41%, adjusted risk ratio (aRR) 3.01 (95% CI 1.63–5.57); HIVST + $10 52%, aRR 3.72 (95% CI 1.85–7.48); both P < 0.001] and phone reminder [22.3%, aRR 1.58 (95% CI 1.07–2.33), P = 0.021]. The study showed the most promise for self-testing with cash incentives for uptake of HIVST and linkage to care among men.
Jubilee et al. described a program of home-based visits for index testing of biological children and sexual partners of PLWH, offering a patient-friendly strategy accommodating flexible hours in Lesotho. Seventy-five percentage of PLWH offered the intervention accepted an index visit and the trial resulted in higher HIV positivity across all groups when compared with nonindex testing. Importantly, linkage rates were higher across all groups accessed through index testing than other HIV testing services (92 vs. 65% in children, 73 vs. 58% in adolescents, and 72 vs. 51% in adults).
A second study of index testing in SSA saw 63% (410) of PLWH linked within 7 days (rapid ART initiation), and 85% linked within 30 days . Participants were 4.1 times more likely to link within 7 days during a period in which ‘expert clients’ assisted with linkage (75% linkage).
The intervention included household index case testing, linkage to care, defaulter tracking, and identification and formation of community ART refill groups. Clients could link to any facility and records were reconciled to determine linkage. For the duration of the study, the number linked increased and the time to link decreased.
To maximize the impact of UTT and achieve UNAIDS targets, substantial gaps in linkage to HIV care must be addressed. Patient-centered care models can increase uptake and maintenance of ART among underserved groups and integrate care for addiction and mental health, as these become increasingly signification sources of comorbidity [17,19,36,37]. As ART programs expand and opportunities increase for PLWH to become ‘lost to follow-up’, re-engagement opportunities or ‘side-doors’ must exist . By focusing on programs for key populations, as well as retention and re-engagement, the global community can directly address barriers to care and more rapidly approach the 90–90–90 targets.
Financial support and sponsorship
This work was supported by the National Institutes of Health: K24 AI141036 and R01 MH108427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was also supported by the Weissman Family Massachusetts General Hospital Research Scholar Award.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
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