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Starting Antiretroviral Therapy in Treatment-Naive Persons Living With HIV

Is as Soon as Possible Good Enough When “Rapid Start” is Clinically Feasible?

Stanton, John Jr, MSN, MPH*; Remiarz, Amelia, MSN, RN; Wright, Phyllis, DNP, MSN, MPH

Journal of the Association of Nurses in AIDS Care: May-June 2019 - Volume 30 - Issue 3 - p 255–258
doi: 10.1097/JNC.0000000000000085
Commentary
Free

John Stanton, MSN, MPH, is a DNP Student, Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA, and a Graduate Research Assistant, PRISM Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA. Amelia Remiarz, MSN, RN, has a Dual Specialty in Acute and Primary Care for Adult Gerontology, Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA. Phyllis P. Wright, DNP, MSN, MPH, is an Assistant Clinical Professor and Adult/Gerontology Primary Care Specialty Coordinator, Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA.

Corresponding author: John Stanton, e-mail: john.l.stanton@emory.edu

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

HIV continues to be a prevalent public health concern across the globe. In the United States, more than 37,000 new HIV diagnoses and 6,000 deaths were reported in 2014, nearly half of which occurred in the southeastern United States (Centers for Disease Control and Prevention, 2017). Diagnosis and treatment initiation for people living with HIV (PLWH) remains an essential skill for all health care providers (Centers for Disease Control and Prevention, 2017). With advances in antiretroviral therapy (ART), and an increasing awareness of the benefits of viral suppression, numerous changes in guidelines for the initiation of ART have taken place. Largely, due to a greater understanding of the benefits of early treatment and research on the safety and efficacy of treatment regimens, the major organizations that set best practice guidelines in HIV treatment recommend that all PLWH receive treatment as soon as possible regardless of CD4+ T-cell count (Table 1; Eholié et al., 2016). The World Health Organization 2018, National Institutes of Health (NIH; U.S. Department of Health and Human Services, 2018), and International Antiviral Society, USA ( Saag, et al., 2018), all updated their guidelines in 2018 to recommend initiating “rapid start” ART for treatment-naive patients as early as possible and, when feasible, on the same day as diagnosis. Unfortunately, clinical providers have been slow to follow the updated guidelines, with little uptake in rapid start programs (Colasanti et al., 2018).

Table 1

Table 1

Several key benefits of rapid start ART have been consistently demonstrated, including decreased time to viral suppression, increased retention in care, and a reduction in morbidity and mortality (Ford et al., 2018). Although evidence has supported the findings that viral suppression eliminates the possibility of transmission, only 57.2% of those diagnosed with HIV have been retained in care, and only 59.8% have achieved viral suppression (Centers for Disease Control and Prevention, 2018).

In 2016, the Undetectable = Untransmittable campaign was launched, acknowledging decades of research demonstrating that HIV cannot be sexually transmitted with an undetectable viral load, defined by the Centers for Disease Control and Prevention as fewer than 200 copies per milliliter (Centers for Disease Control and Prevention, 2018; Editorial: U=U taking off in 2017, 2017). In a San Francisco-based study examining the impact of a rapid care initiation protocol on outcomes in PLWH, researchers found that the median time to virologic suppression was 56 days among rapid start patients compared to 79 days in those treated under more general guidelines for universal ART initiation (p = .009; Pilcher et al., 2017). This result was supported by the work of Colasanti et al. (2018), who found a median decrease in time to viral suppression from 77 to 57 days (p < .0022) in the standard care and rapid start groups, respectively.

Although variations in baseline viral load and CD4+ T-cell count may ultimately impact the overall time to viral suppression, baseline viral load and the risk of HIV transmission have been positively correlated, underscoring the importance of addressing treatment at the earliest possible time (Cohen et al., 2011). By targeting a minimal to lower initial viral load and a significantly decreased time to viral suppression, rapid start ART can positively affect the health of the individual and, by potentially reducing transmission, the greater public health community.

Current practice varies widely among clinics, with providers often seeing patients over multiple visits to complete confirmatory testing, laboratory testing, and selection of an ART regimen. This multistage process of treatment initiation increases the risk of losing patients to follow up, leaving patients with higher viral loads, and increasing transmission risks (Rosen & Fox, 2011). In examining this sequential, and possibly siloed, approach to care, Rosen and Fox (2011) identified three distinct intervals of care: (a) testing positive for HIV and receiving laboratory results, (b) enrollment in pre-ART care and the determination of eligibility for ART, and (c) treatment initiation. A systematic review of the literature demonstrated that less than one third of patients who begin this process were retained continuously in care, identifying a key area of opportunity for rapid start (Rosen & Fox, 2011).

Current evidence examining rapid start has provided support for the practice as a means of increasing patient uptake of ART and boosting retention in care across all settings and populations. The CASCADE trial identified a 15% (p = .01) increase in patients who remained in care at 1 year when offered ART on the day of diagnosis (Labhardt et al., 2018). Additionally, the literature has supported findings that early treatment initiation increased frequency of visits, which was correlated with improved retention and shortening time to viral suppression (Hall, Tang, Westfall, & Mugavero, 2013).

With the aforementioned reduction in viral load and increased retention in care seen in studies examining rapid start, a decrease in morbidity and mortality in these patients seems a natural consequence. Although not the primary end point of most rapid start studies, earlier treatment intervention has validated changes in the treatment guidelines to begin ART irrespective of CD4+ T-cell count. The START trial demonstrated increased subsequent CD4+ T-cell count from baseline, resulting in a decreased likelihood of common opportunistic infections, such as tuberculosis, Kaposi sarcoma, and malignant lymphomas (INSIGHT START Study Group, 2015).

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Discussion

Common to any change in clinical practice, widespread adoption of rapid start ART is not without concerns, and these concerns must be acknowledged. International Antiviral Society—USA has questioned the feasibility of the more resource-intensive nature of rapid start. However, multiple model clinics demonstrated that early initiation of ART was feasible as a new standard of practice without significant investment in increased clinical resources (Saag et al., 2018; U.S. Department of Health and Human Services, 2018). Furthermore, research has now begun to demonstrate that long-held beliefs about patients not being ready to start treatment on the day of diagnosis may be outdated. In a San Francisco-based cohort of newly diagnosed patients, 89.7% of patients who were offered ART at their first visit took their first dose before leaving the clinic and 94.9% began treatment within 24 hours of their initial visit (Pilcher et al., 2017). Koenig et al. (2017) noted that nearly 100% of patients who were screened for rapid start reported readiness to begin lifelong ART.

Providers may have concerns about rapid start protocols because of the potential for adverse drug-related effects or apprehensions about choosing an appropriate initial regimen for a treatment-naive individual. The literature has suggested that fears related to implementing rapid start without complete laboratory work-up may be unfounded. In analysis of laboratory results returned after rapid start, less than 1% of patients were found to have conditions that were concerning for immune reactivation inflammatory syndrome, which would have warranted a treatment delay (Koenig et al., 2017). Furthermore, only 4% of patients had creatinine clearance values less than 50 ml/min that was undiagnosed at the time of treatment initiation, decreasing concerns with regard to patients who might require renal dose adjustments (Koenig et al., 2017).

When considering implementation of a rapid start protocol, medications with a low relative likelihood of adverse reactions, including those that could be started without the results of complex laboratory testing, should be used (Pilcher et al., 2017). Providers should become comfortable with one or two regimens currently recommended for immediate start. Recently updated NIH guidelines suggest that an initial regimen of bictegravir + tenofovir alafenamide + emtricitabine (Biktarvy) can be safely started in most treatment-naive patients (U.S. Department of Health and Human Services, 2018).

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Conclusion

There should be no debate if initiating ART is appropriate for all PLWH considering the opportunities to improve viral suppression, increase retention in care, and slow disease progression and mortality. Results of early pilot studies suggest that initiating rapid start, or same-day, treatment for patients is an innovative way to simultaneously improve patient outcomes and broader public health goals of reducing HIV transmission. Clinicians need to advocate for the dissemination of rapid start protocols and inclusion of clear algorithms in treatment guidelines. Same-day initiation of ART in treatment-naive individuals can be the standard that practice clinics aim to achieve. By rapidly reducing viral loads, preventing an expanding foothold through delays in treatment initiation, it may be possible to do more than improve the quality of life of PLWH; it may also be possible to slow transmission moving us closer to an HIV-free generation.

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Disclosures

The authors report no real or perceived vested interests relating to this article that could be construed as a conflict of interest.

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Acknowledgments

The authors acknowledge assistant professors Phyllis Wright, AGPCNP, DNP, MPH, and Philip Davis, DNP, MBA, ANP-BC, for their roles in adding a scholarship component to the traditionally clinically focused Adult-Gerontology Nurse Practitioner program.

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