Evaluation of Xpert point-of-care assays for detection of HIV infection in persons using long-acting cabotegravir for pre-exposure prophylaxis

Abstract

Detection of HIV infection may be challenging in persons using long-acting cabotegravir (CAB-LA) pre-exposure prophylaxis (PrEP) due to viral suppression and reduced/delayed antibody production. We evaluated two point-of-care tests for detecting HIV infection in persons who received CAB-LA in the HPTN 083 trial. Samples were obtained from 12 participants who received CAB-LA and had delayed detection of HIV infection using HIV rapid tests and an antigen/antibody test (52 plasma samples; 18 dried blood spot [DBS] samples). Plasma samples were tested with the Xpert HIV-1 Viral Load XC test (Xpert VL-XC); DBS samples were tested with the total nucleic acid Xpert HIV-1 Qual XC test (Xpert Qual-XC). Results from these assays were compared to results from three reference, laboratory-based, plasma RNA assays (Aptima HIV-1 Qualitative assay [Aptima Qual]; Aptima HIV-1 Quant DX Assay [Aptima Quant]; cobas HIV-1/HIV-2 Qualitative Test [cobas]). HIV RNA was detected with all four plasma assays for all samples with viral loads (VLs) ≥ 200 copies/mL; the number of samples with VLs < 200 copies/mL with HIV RNA detected was: Xpert VL-XC: 19/26 (73.1%); Aptima Qual: 17/26 (65.4%); Aptima Quant: 17/26 (65.4%); and cobas: 12/21 (57.1%). The Xpert Qual-XC assay was positive for all DBS samples with VLs ≥ 200 copies/mL and 1/10 DBS with VLs < 200 copies/mL. The performance of the Xpert VL-XC assay was comparable to the reference assays for detecting HIV infection in these cases. The Xpert Qual-XC assay was less sensitive than plasma-based HIV RNA assays for detecting HIV in the setting of CAB-LA PrEP.

Importance: HIV RNA assays can detect HIV infections earlier than HIV rapid tests or Ag/Ab tests in persons using CAB-LA PrEP. Earlier HIV diagnosis could allow for earlier treatment initiation and reduced risk of INSTI resistance. POC tests may help detect HIV infection before CAB-LA administration and may be more accessible than laboratory-based assays in some settings. In this study, the POC Xpert VL-XC assay detected HIV RNA in most samples from individuals who received CAB-LA PrEP and had delayed detection of HIV infection with HIV rapid tests and an Ag/Ab test. The performance of this assay was similar to laboratory-based HIV RNA assays in this cohort. The POC Xpert Qual-XC assay detects both HIV RNA and DNA, with a higher viral load cutoff for RNA detection. This assay was negative for most lower viral load samples and did not offer an advantage for HIV screening in persons using CAB-LA PrEP.

Keywords: HIV prevention; HPTN 083; RNA; long-acting cabotegravir; point-of-care; pre-exposure prophylaxis.

Fig 1

The figure shows the approach used to select samples for testing. In HPTN 083, 2,282 participants were randomized to the cabotegravir (CAB) arm. These participants were followed for 3,204 person-years during the blinded phase of the trial and 1,456 person-years during the first year after study unblinding (total: 4,660 person-years). Thirty-four HIV infections were identified between the start of the trial and the end of the first unblinded year. Sixteen of these participants acquired HIV within 6 months of a long-acting CAB (CAB-LA) injection. In 12 of those cases, detection of HIV infection was delayed at the study site using HIV rapid tests and an antigen/antibody test. Samples from those 12 cases were used for analysis in this study. The samples from these cases were collected in the HPTN 083 trial for Virology and Pharmacology assessments related to the study objectives. This study used plasma samples remaining after those assessments were completed. Some samples did not have sufficient plasma for testing with all of the assays evaluated in this report. Fifty-two plasma samples and 18 dried blood spot (DBS) samples were stored for these 12 participants on and after the first HIV-positive visit. Cases were excluded from the analysis if results were obtained for only one or two of the four plasma assays. The final sample set included 45 plasma and 16 DBS (see File S2). Abbreviations: CAB: cabotegravir; CAB-LA: long-acting injectable CAB; DBS: dried blood spots; pos: positive.