The Conference on Retroviruses and Opportunistic Infections (CROI) 2019 was held recently in Seattle, Washington, United States, and one of the highlights of the meeting was the long-term management of patients who are infected with the human immunodeficiency virus (HIV). As there is an increasing number of people living with HIV (PLHIV) undergoing antiretroviral therapy (ART) and the World Health Organization (WHO) initiative of 90-90-90 targets (90% of all PLHIV will know their HIV status, 90% of PLHIV diagnosed will be on ART, and in which 90% of them will be virologically suppressed) to be achieved by the year 2020, novel continuous monitoring methods are warranted. Data from a randomized controlled trial demonstrated the efficacy of point-of-care (POC) viral load (VL) testing in maintaining suppressed VLs, as well as enhancing retention in care.
Why the HIV epidemic is not over
In 2017, 1.8 million people were newly infected with HIV.1 While the world has committed to ending AIDS by 2030, rates of new infections and deaths are not falling rapidly enough to meet the target.1 From the beginning of the HIV/AIDS epidemic, more than 70 million people have been affected with the HIV virus and about 35 million people have died of HIV.2 Globally, 36.9 million people were living with HIV at the end of 2017.2 Nonetheless, an estimated 0.8% of adults aged 15-49 years worldwide are living with HIV and the burden of the epidemic continues to vary considerably between countries and regions.2 In Hong Kong, a total of 624 cases of HIV infection were reported to the Centre for Health Protection of the Department of Health in 2018, whereas it was 681 in 2017.3
ART for all people with HIV: WHO recommendation
ART consists of a combination of antiretroviral (ARV) drugs to maximally suppress the HIV virus, to halt the progression of HIV disease (Figure 1) and to prevent onward transmission of HIV.4 As a significant reduction has been observed in death rates and subsequent infections with ARV regimen, particularly in the early stages of the disease, WHO recommends ART for all PLHIV as soon as possible after diagnosis without any restrictions of CD4 counts,4 hence aligning with the Joint United Nations Programme on HIV and AIDS (UNAIDS) 90-90-90 targets to be achieved by the year 2020.4
Effective follow up with quantitative VL: POC VL testing vs. laboratory VL testing
Rapid access to ART has been observed, from just 2.1 million people undergoing ART in 2005 to 21.7 million by the end of 2017.4 The increased survival as a result of ART has led to an increasing number of PLHIV, whom are in need of continuous monitoring. Henceforth, many health systems in low to middle income countries are facing crisis as they are operating at their maximum capacities and struggling to provide care for more HIV positive patients without compromising chronic HIV care of PLHIV.4 Therefore, it has also led to other operational issues, including longer waiting times, which could jeopardize the chance of achieving the 90-90-90 targets.4
In fact, many clinics are still not equipped to provide effective and patient-centered chronic care facilities as the ongoing models of HIV care were designed in the era, where efficient ART was not available.5 In order to meet these challenges in maintaining chronic care for HIV patients under ART, newer models have been introduced.6 These models include adding more relevant health care facilities and community based strategies involving elements of task shifting, less frequent clinic visits and/or decentralized ART distribution.7 Moreover, frequent quantitative VL testing should be required for triaging stable HIV-positive patients in differentiated care models, which is the most effective method of monitoring the response to ART as recommended by the WHO.7
According to the WHO recommendations, VL monitoring should be performed at 6 and 12 months after the ART initiation and then annually.7 As per the current standard of care, laboratory VL testing prevails, but the laboratory capacity to VL testing varies, for example, while 75% of PLHIV on ART in South Africa have at least one VL performed, but only 10% in Uganda and 38% in Kenya were doing so.8 When considering global statistics, millions of patients under ART do not know their viral levels.9 Therefore the traditional laboratory VL assay, which takes days to deliver the results, would not be able to compensate the increasing demand of VL testing among PLHIV.10 As a result, there is a growing interest towards POC VL assays, a rapid on-site VL testing, which could alleviate the burden on central laboratory services and improve the clinical management by providing test results while the patient is still at the clinic.10
POC VL testing improves the suppression rate of HIV
Recent findings from an open-label and randomized controlled trial conducted at the city of Durban, South Africa, were presented at the CROI, which showed that on the spot POC VL testing was able to suppress VL among PLHIV and allow them to stick to the treatment continuously.11 Participants were adults ≥18 years and enrolled into the trial 6 months after the ART initiation at an urban public clinic, and were randomized to receive either POC VL testing (Xpert® HIV-1 VL, Cepheid) and same day counselling or standard-of-care laboratory VL testing.11 The follow up time was 12 months and they all received similar HIV care according to the South African guidelines, which included clinic visits every 2 months, VL testing at months 6 and 12 after the ART initiation and decentralized ART delivery at community pharmacies 1 year after the initiation of ART.11 The primary outcome was retention in care with VL suppression at month 12 through a load of <200 copies/mL.11
“The composite primary end points of viral suppression were achieved in 89.7% of patients assigned to POC testing versus 75.6% of patients whose tests were done at the laboratory (95% CI: 6.4-21.2; p<0.01)”, stated by the principal investigator of the study, Dr. Paul Drain, MD, University of Washington, United States. Furthermore, he explained “retention in care, by itself, was also improved in the POC testing group, by 7.7 % (92.3% vs. 84.6%, p=0.03)”.12
As POC testing of VL significantly improved HIV viral suppression and retention in care due to the instant receipt of VL results to patients as well as care providers, Dr. Drain is positive that increasing access to POC testing could help achieve the 90-90-90 targets.12 It is also worthy to note that participants in the POC arm had a 3.4-fold (95% CI: 2.5-4.8) higher rate of entry into decentralized ART delivery.11 This indicates the abrupt referral to ART when higher VLs were observed as a result of discontinuation of ART by the patients.11
Dr. Drain further commented, “Most people did well in taking their medications and keeping the virus suppressed,” and he emphasized the role of POC in keeping low VL as, “What POC testing does is that it helps us identify the patients who are not doing well, and we can attend to them immediately.12 Whether it is in South Africa or in Seattle once they leave the clinic – especially talking about people who are having challenges with their therapy – it is very hard to reach them and get them back to the clinic.”12
In the light of these findings, the moderator of the conference, Dr. Susan Buchbinder, MD, University of California, San Francisco remarked “POC testing could have some benefits in the U.S. setting”.12 According to Dr. Buchbinder, in United States, early identification of individuals with higher VLs is difficult and it is important to have more information at hand when initiating interventions among these individuals. Consequently Dr. Buchbinder added “We are beginning to get POC testing here for sexually transmitted infections. They are being rolled out in a variety of different settings”.12
According to Dr. Drain, only 50% of people on ART achieved viral suspension globally. “We felt that one of the reasons for the failure to achieve viral suppression is the long waiting time of obtaining laboratory VL results in clinical settings. Our objective in this randomized trial was to do POC VL testing to see if we could improve virus suppression,” said Dr. Drain.12
Drain and colleagues randomized 390 patients in the open-label study, assigning 195 to receive the POC VL tests. When the results came back in 2-3 hours, in the POC VL arm, clinicians reviewed them immediately with the patients. In contrast the patients whose VL testing was done in the laboratory had to wait for their next appointment for the results and consultation, which was approximately 28 days. From the patients’ perspectives, POC VL testing was significantly more comfortable, thus “Almost everybody was willing to wait for their VL results,” revealed Dr. Drain.12
According to the clinical trial results shared at CROI 2019, long-term suppression of VL and retention in care were experienced when constant POC VL monitoring was rendered in PLHIV. POC in assessing VL among PLHIV could be implemented in any clinical setting effectively and could help to achieve the WHO 90-90-90 targets. In conclusion, instant POC VL testing at hand may allow clinicians to closely assess the compliance of PLHIV to ART therapy and take actions instantaneously. They may consider incorporating POC VL testing in standard of care for more effective monitoring of PLHIV moving forward.
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8. Lecher S, Williams J, Fonjungo PN, et al. Progress with Scale-Up of HIV Viral Load Monitoring – Seven Sub-Saharan African Countries, January 2015-June 2016. MMWR Morb Mortal Wkly Rep. 2016;65(47):1332-5.
9. Peter T, Ellenberger D, Kim AA, et al. Early antiretroviral therapy initiation: access and equity of viral load testing for HIV treatment monitoring. Lancet Infect Dis. 2017;17(1):e26-e9.
10. Shafiee H, Wang S, Inci F, et al. Emerging technologies for point-of-care management of HIV infection. Annu Rev Med. 2015;66:387-405.
11. Drain PK, Dorward J, Violette L, et al. Abstract. Point-of-care viral load testing improves HIV viral suppression and retention in care. Conference on Retroviruses and Oppertunistic Infections; March 4 2019; Seattle, washington.
12. Point-of-Care HIV Load Testing Keeps Patients at Clinic, MEDPAGE TODAY. (Accessed March 13 at https://www.medpagetoday.com/meetingcoverage/croi/78395)