Abstract
Background
The Alere q HIV-1/-2 Detect test (Alere Detect) is a rapid point-of-care (POC) nucleic acid test (NAT) that can detect and differentiate HIV-1 and HIV-2 in 25-µL whole blood or plasma samples. The Alere Detect test has been validated for early infant diagnosis of HIV-1 infection, and it is the only POC NAT device currently known to detect HIV-2, which is endemic in West Africa.
Objectives
To evaluate the sensitivity detecting HIV-2 RNA and the differential performance of the Alere Detect.
Study Design
Plasma samples from non-HIV (n=4), HIV-1 (n=22), HIV-2 (n=111; 29 Group A, 2 Group B) and HIV-1/HIV-2 dually-seropositive (n=8) participants in Senegal and the United States and HIV-2 reference strains (3 Group A, 1 Group B) were tested by Alere Detect, Abbott RealTime HIV-1 and the University of Washington HIV-2 RNA quantitative (UW HIV-2) assays.
Results
The Alere Detect correctly differentiated between HIV-1 and HIV-2 in all 80 (100%) patient samples with detectable HIV RNA (n=20 HIV-1, 60 HIV-2). The overall HIV-2 detection concordance between Alere Detect and the UW HIV-2 assay was 68% (54/80); the concordance improved to 100% (30/30) for samples with HIV-2 RNA >300copies/mL. Neither assay detected HIV-2 RNA in 31 of 111 HIV-2 seropositive samples.
Conclusions
The Alere Detect test is a novel device detecting HIV RNA in clinical samples, and differentiating HIV-1 and HIV-2 with a high level of specificity. It has the potential for use as a rapid HIV-2 NAT-based diagnosis tool in resource-limited settings and to confirm HIV-2 infection for the CDC 4th generation HIV-1/2 diagnostic algorithm.
Keywords: HIV-2, diagnosis, point-of-care, nucleic acid test, Alere q HIV-1/-2 Detect, qualitative
BACKGROUND
HIV-2 is endemic in West Africa with limited global spread primarily to countries with socioeconomic ties to the region (1–4); there are an estimated 1–2 million patients infected with HIV-2 worldwide (5–7). Compared to HIV-1, patients infected with HIV-2 often have a longer asymptomatic stage, slower decline in CD4+T-cells and decreased acquired immunodeficiency syndrome (AIDS)-associated mortality (8–11). In areas where HIV-2 and HIV-1 co-circulate, a substantial number of patients are dually-infected with both HIV types (12–14). The correct differentiation between HIV-1 and HIV-2 infection is critical for diagnosis, antiretroviral therapy (ART) and medical management of HIV-infected individuals (15).
Current methods for distinguishing between HIV-1 and HIV-2 rely on differential immunoassays with varying sensitivity and specificity (16, 17). The Alere q HIV-1/-2 Detect (Alere Detect) test is a rapid point-of-care (POC) nucleic acid test (NAT) providing several advantageous characteristics for HIV diagnosis: 1) the requirement for only 25 microliters plasma or whole blood per test; 2) test completion within one hour; 3) detection and differentiation of HIV-1 Group M/N, HIV-1 Group O and HIV-2 nucleic acid; and 4) the only currently available POC NAT able to detect HIV-2 (18). Two studies have demonstrated the feasibility of the Alere Detect test to diagnose HIV-1 infection for HIV-1-exposed infants in South Africa and Mozambique (19, 20). Here, we evaluated the performance of the Alere Detect test for the detection of HIV-1 and HIV-2 in plasma samples collected from HIV-1, HIV-2 and differentiation of HIV-1 from HIV-2, in dually-seropositive patients.
OBJECTIVES
Our objectives were to evaluate the sensitivity detecting HIV-2 RNA in plasma samples and the differential performance between HIV-1 and HIV-2 RNA by the Alere q HIV-1/-2 Detect.
STUDY DESIGN
Patient HIV samples and controls
Clinical plasma samples from HIV-seronegative, HIV-1, HIV-2 and HIV-1/HIV-2 dually-seropositive patients from Senegal and the United States were tested. All study subjects were provided written informed consent, and specimens were collected with human subject approval from the UW Institutional Review Board and the Senegalese Ministry of Health Ethic Committee (CNERS). All clinical specimens were de-identified as required by the UW Humans Subjects Division.
Senegalese HIV-2 and HIV-1/HIV-2 dual-seropositive patient plasma samples were collected as part of ongoing studies of HIV-2 infection in antiretroviral (ARV)-naïve subjects and antiretroviral treated subjects as part of the Senegalese Government Antiretroviral Program (ISAARV) (www.cnls-senegal.org) at the Clinique Des Maladies Infectieuses et Tropicales Ibrahima DIOP MAR, Dakar, and the Centre de Sante, Ziguinchor, Senegal (21–23). Collected HIV seronegative and HIV-1 seropositive samples were from discarded clinical samples tested by the University of Washington (UW) Clinical Retrovirology Laboratory. Reference strains of HIV-2NIH-Z, HIV-2ROD and HIV-2EHO viral stocks were diluted in human HIV-negative plasma to nominal 12,000 copies/mL, 500 copies/mL, and 500 copies/mL, respectively.. WHO HIV-2 RNA International Standard, containing HIV-2CAM-2 strain, were reconstituted using molecular grade water to 1000 units/mL. HIV-seropositive status for Senegalese participants was determined using Determine (Alere, Inc., USA) and Immunocomb II (Orgenics, Israel) immunoassays. The status of discarded clinical plasma samples was determined using the BioRad GS HIV-1 Western blot kit or the Multispot HIV-1/HIV-2 Rapid Test (BioRad, USA).
HIV-1 and HIV-2 RNA in plasma samples was quantified by the Abbott RealTime HIV-1 assay (Abbott HIV-1 assay) (Abbott Molecular, USA) and the clinically validated UW-Abbott m2000 HIV-2 RNA quantitative assay (UW HIV-2 assay), respectively (24).
Alere q HIV-1/2 Detect and Alere q Analyzer
Each Alere Detect test consisted of a single-use cartridge that contained reagents for the capture and amplification of HIV-RNA. After loading the sample capillary with 25 µL of plasma, each cartridge was inserted into an Alere q Analyzer where RNA isolation, cDNA synthesis, PCR and signal detection occur. The Alere q Analyzer reported either “detected” or “not detected” results for HIV-1 Group M/N, HIV-1 Group O and HIV-2 (18). The tests described in this study were carried out using four Alere q Analyzers in the Clinical Laboratory Improvement Amendments (CLIA)-certified and College of American Pathologists (CAP)-accredited UW Clinical Retrovirus laboratory.
RESULTS
Qualitative detection of HIV-2 RNA in plasma samples
Of 111 plasma samples collected from HIV-2 seropositive patients, 31 samples (27.9%) were not detected by either the Alere Detect or the UW HIV-2 assay (Table 1). Of the 80 total samples detected or quantified by the UW HIV-2 assay (median=108 copies/mL, range: <10 to 96,000 copies/mL), 54 samples (67.5%) were detected by the Alere Detect. The overall concordance for detection between the Alere Detect and the UW HIV-2 assay was 54/80 (68%; 95%CI. 56.1% to 77.6%); the concordance improved to 42/46 (91%; 95%CI, 79.2% to 97.6%) for samples with HIV-2 RNA level >50 copies/mL and to 30/30 (100%; 95%CI lower bound 90.5%) for samples with >300 HIV-2 RNA copies/mL.
Table 1.
Detection of HIV-2 RNA in HIV-2 seropositive plasma samples by Alere Detect.
| UW HIV-2 RNA assay* | |||||
|---|---|---|---|---|---|
| Not Detected |
<50 copies/mL |
50–300 copies/mL |
>300 copies/mL |
||
| 31 | 34 | 16 | 30 | ||
| Alere Detect | HIV-2 Detected | 0 | 12 | 12 | 30 |
| HIV-2 Not Detected | 31 | 22 | 4 | 0 | |
The sensitivity of the assay was determined to be 8 copies/mL (95% CI, 5–18 copies/mL) (24)
Of the 22 HIV-1 plasma samples with RNA levels detected or quantified by the Abbott HIV-1 assay (median=663 copies/mL, range: <40 to 31,000 copies/mL), the overall concordance for detection between the Alere Detect and the Abbott HIV-1 assay was 17/22 (77%; 95%CI, 54.6% to 92.2%); the concordance was 17/20 (85%; 95% CI, 62.1% to 96.8%) for plasma samples with HIV-1 RNA levels >50 copies/mL and 13/13 (100%; 95%CI lower bound 79.4%) for samples >300 HIV-1 RNA copies/mL.
Differentiation between HIV-1 and HIV-2
To evaluate assay capability, a total of 149 samples, including 4 HIV-seronegative, 22 HIV-1 seropositive, 111 HIV-2 seropositive, 8 dual HIV-1/HIV-2 seropositive and 4 HIV-2 reference strains, were tested using the Alere Detect (Table 2). The Alere Detect accurately differentiated between HIV-1 and HIV-2 in 100% of 80 samples with detectable HIV RNA (20 HIV-1, 60 HIV-2) and had no misclassification errors in samples with undetectable HIV RNA (5 HIV-1; 58 HIV-2; 4 HIV-seronegative).
Table 2.
HIV-infected plasma samples and HIV-2 viral stocks tested by Alere Detect
| HIV status | Number of plasma samples tested |
HIV-1 M/N result* | HIV-2 result | ||
|---|---|---|---|---|---|
| Undetected | Detected | Undetected | Detected | ||
| HIV seronegative | 4 | 4 | 0 | 4 | 0 |
| HIV-1 seropositive | 22 | 5 | 17 | 22 | 0 |
| HIV-2 seropositive | 111^ | 111 | 0 | 57 | 54 |
| HIV-1 and HIV-2 dual seropositive | 8 | 5 | 3 | 5 | 3 |
| HIV-2 laboratory strain& | 4 | 4 | 0 | 0 | 4 |
No samples were detected for HIV-1 Group O.
Samples were collected from 94 participants; among them, 29 were infected by HIV-2 Group A, 2 by Group B and 1 by HIV-2 A/B recombinant virus, while the genotypes of HIV-2 infecting the rest of the participants were not determined.
HIV-2NIH-Z, HIV-2ROD and HIV-2EHO and HIV-2CAM-2 viral stocks.
In addition, 8 HIV-1/HIV-2 dually-seropositive plasma samples were tested using the Alere Detect, and their HIV-1 and HIV-2 RNA levels were measured using the Abbott HIV-1 and the UW HIV-2 assays, respectively (Table 3). Samples HD02 and HD06 had detectable HIV-1 M/N and HIV-2 (both HIV-1 and HIV-2 RNA levels were greater than 300 copies/mL). Neither HIV-1 nor HIV-2 was detected by the Alere Detect test in HD01, HD09, HD12, and HD14 (these samples all had undetectable HIV RNA levels). HIV-2 was detected by the Alere Detect test and the UW HIV-2 assay, while HIV-1 RNA was too low to be detected by the Alere Detect test in HD13. In the sample collected from HD10, only HIV-1 RNA was detected by the Alere Detect test and the Abbott HIV-1 assay; however, HIV-2 RNA was not detected by either the Alere Detect test or the UW HIV-2 assay.
Table 3.
Testing HIV-1/HIV-2 dually-seropositive samples
| Dual HIV-1/HIV-2 Seropositive Samples (collection date) |
HIV-1 Alere Detect Qualitative Result* |
HIV-2 Alere Detect Qualitative Result |
HIV-1 Abbott Results RNA copies/mL^ |
HIV-2 UW- Abbott Results RNA copies/mL^ |
|---|---|---|---|---|
| HD01 (07.14.10) | Undetected | Undetected | Undetected | Undetected |
| HD02 (05.04.09) | HIV-1 M/N detected | Detected | 85,120 | 2,592 |
| HD06 (09.29.09) | HIV-1 M/N detected | Detected | 510,596 | 311 |
| HD09 (01.06.11) | Undetected | Undetected | Undetected | Undetected |
| HD10 (01.06.11) | HIV-1 M/N detected | Undetected | 13,730 | Undetected |
| HD12 (08.11.11) | Undetected | Undetected | Undetected | Undetected |
| HD13 (09.08.11) | Undetected | Detected | Detected, <40 | 28,726 |
| HD14 (04.28.11) | Undetected | Undetected | Undetected | Undetected |
All samples were not detected for HIV-1 Group O.
Some results listed below were previously published (31).
DISCUSSION
In this study, we evaluated the ability of the Alere q HIV-1/2 Detect, a rapid POC NAT platform, to detect and differentiate HIV-1 from HIV-2 RNA in plasma samples collected from HIV-infected persons. To our knowledge, this is the first study of a device that detects and differentiates HIV-1 and HIV-2 nucleic acid, which makes this device suitable for use in HIV-2 endemic regions. The 4th-generation (2014) CDC algorithm for HIV diagnostic testing differentiates HIV-1 from HIV-2 infection (25), which is important for improving diagnostic specificity of unknown or unrecognized and misclassified cases of HIV-2 infection (4). However, one of the unaddressed issues with the 2014 CDC algorithm is the lack of an available and FDA-approved HIV-2 NAT to confirm HIV-2 positive serology and to help determine whether dually HIV-1/HIV-2 reactive or seropositive (so-called “HIV-undifferentiated”) individuals are infected with either HIV-1 or HIV-2 or both. Our study demonstrates that the Alere Detect test correctly identified HIV-1 M/N and/or HIV-2 with high specificity in 100% of 80 samples with detectable HIV-1 or HIV-2 RNA or both. This unique capability may be useful for reducing the serological misdiagnosis of HIV-2 infection.
The Alere Detect test was first investigated for early infant detection (EID) in Mozambique and South Africa (19, 20). In these two studies, heel-stick blood samples were tested by the Alere Detect test and the Roche COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 Qualitative Test (Roche HIV-1 qualitative test). The combined sensitivity and specificity of the POC Alere Detect test were 97% and 99%, respectively, compared to the high-throughput Roche HIV-1 qualitative test. Though the detection limit for whole blood samples has not been published, the sensitivity of the Roche HIV-1 qualitative assay for dried blood spots was reported to be 300 copies/mL (26). Our study yielded results with similar sensitivity: all 13 of the plasma samples, which contained more than 300 copies/mL measured by the Abbott HIV-1 assay, were detected by the Alere Detect test. Our study further showed that the detection limit of the Alere Detect for HIV-2 RNA in plasma samples was similar: 30 of 30 HIV-2–seropositive plasma samples that contained >300 copies/mL HIV-2 RNA were all detected by the Alere Detect. The vast difference of input volumes between the Alere Detect (25 µL) assay and the UW HIV-2 assay (1000µL) influenced the concordance of HIV-2 RNA detection between these two assays. The generation of positive results for samples with >300 HIV-2 RNA copies/mL indicated the ability for the Alere Detect assay to detect ≥ 8 copies HIV-2 RNA in 25 µL plasma samples. In addition, other HIV POC NAT platforms have been documented to detect HIV-1 only, such as the Liat HIV Quant (27, 28) and Cepheid Xpert HIV-1 Qual (29, 30) assays. The Alere Detect test is the only POC device at this time that is currently able to detect HIV-2, which makes it potentially suitable for the detection of HIV-2 infection in mother-to-child transmissions (PMTCT) programs, especially in West Africa; however, formal clinical studies are required to validate the utility of this device in HIV-2 endemic areas.
In conclusion, the Alere q HIV-1/2 Detect test is designed to use small volume samples (25 µL of either finger prick or venous whole blood or plasma) and may also serve as a rapid HIV NAT-based diagnostic test in resource-limited settings. Importantly, the Alere q HIV-1/2 Detect device provides for important NAT confirmation of serologically defined HIV-2 infection and distinguishes HIV types in serologically “undifferentiated” HIV infection, which is required to address a deficiency in the specificity of the contemporary 2014 CDC algorithm for HIV diagnostic testing (25, 31).
Highlights.
The Alere q HIV-1/-2 Detect, a rapid point-of-care nucleic acid test.
Qualitatively detect and differentiate HIV-1 and HIV-2 in whole blood or plasma samples.
Acknowledgments
FUNDING: NIH/NIAID AI060466, AI027757, AI106701 & AI068618; Alere Technologies, GmbH, Germany.
We thank the study participants, families and study staff. The members of the UW-Dakar HIV-2 Study Group also includes: Fatou Traore, Khadim Faye, Marie Pierre Sy, Bintou Diaw, Mbaye Ndoye, Amadou Bale Diop, Marianne Fadam Diome (Clinique des Maladies Infectieuses Ibrahima DIOP Mar, CHNU Fann, Universite Cheikh Anta Diop de Dakar, Dakar, Senegal); Jean Philippe Diatta, Raphael Bakhoum, Juliette Gomis, (Région Médicale de Ziguinchor, Ziguinchor, Casamance, Senegal), Stephen Hawes, Noelle Benzekri, John Lin, Nancy Kiviat, Jim Mullins, Sally Leong, Sara Masoum and Vincent Wu (UW, Seattle). Thanks to UW Clinical Retrovirology Lab: Glenda Daza, Carol Gallardo, Eleanor Espinosa, Reggie Gausman, Yuree NamKung, Audrey Wong and Mariko Seilie. This study was supported by grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (AI-060466) and Alere Technologies, GmbH (GSG); and the University of Washington Center for AIDS Research (AI-027757) and AIDS Clinical Trials Group Laboratory Center (AI-106701) (RWC) and AI-068618. Financial Disclosures: Dr. Gottlieb has received funding and research support from Gilead Sciences (USA), Merck & Co. (USA), Janssen Pharmaceutica (Belgium), Cerus Corp. (USA), Alere, GmbH (Germany) and Abbott Molecular Diagnostics (USA) for HIV-2 related research.
Footnotes
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COMPETING INTERESTS: None
ETHICAL APPROVAL: UW IRB and the Senegal EC (CNERS)
These findings were presented in part at CROI, February 23–26, 2015, Seattle, WA, Abstract # 614. http://www.croiconference.org/sessions/poc-alere-q-hiv-12-detect-test-detection-and-quantification-hiv-2
References
- 1.De Cock KM, Adjorlolo G, Ekpini E, Sibailly T, Kouadio J, Maran M, et al. Epidemiology and transmission of HIV-2. Why there is no HIV-2 pandemic. JAMA : the journal of the American Medical Association. 1993;270(17):2083–6. doi: 10.1001/jama.270.17.2083. [DOI] [PubMed] [Google Scholar]
- 2.Campbell-Yesufu OT, Gandhi RT. Update on human immunodeficiency virus (HIV)-2 infection. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2011;52(6):780–7. doi: 10.1093/cid/ciq248. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Gottlieb GS, Eholie SP, Nkengasong JN, Jallow S, Rowland-Jones S, Whittle HC, et al. A call for randomized controlled trials of antiretroviral therapy for HIV-2 infection in West Africa. AIDS. 2008;22(16):2069–72. doi: 10.1097/QAD.0b013e32830edd44. discussion 73-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.HIV-2 Infection Surveillance--United States, 1987–2009. MMWR Morbidity and mortality weekly report. 2011;60(29):985–8. [PubMed] [Google Scholar]
- 5.Arien KK, Abraha A, Quinones-Mateu ME, Kestens L, Vanham G, Arts EJ. The replicative fitness of primary human immunodeficiency virus type 1 (HIV-1) group M, HIV-1 group O, and HIV-2 isolates. Journal of virology. 2005;79(14):8979–90. doi: 10.1128/JVI.79.14.8979-8990.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Gottlieb GS. Changing HIV epidemics: what HIV-2 can teach us about ending HIV-1. AIDS. 2013;27(1):135–7. doi: 10.1097/QAD.0b013e32835a11a4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.UNAIDS. UNAIDS AIDS epidemic update 2006. Vol. 2006. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization (WHO); 2004. pp. 1–94. [Google Scholar]
- 8.Poulsen AG, Aaby P, Larsen O, Jensen H, Naucler A, Lisse IM, et al. 9-year HIV-2-associated mortality in an urban community in Bissau, west Africa. Lancet. 1997;349(9056):911–4. doi: 10.1016/S0140-6736(96)04402-9. [DOI] [PubMed] [Google Scholar]
- 9.van Tienen C, Schim van der Loeff M, Peterson I, Cotten M, Andersson S, Holmgren B, et al. HTLV-1 and HIV-2 infection are associated with increased mortality in a rural West African community. PloS one. 2011;6(12):e29026. doi: 10.1371/journal.pone.0029026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Ariyoshi K, Jaffar S, Alabi AS, Berry N, Schim van der Loeff M, Sabally S, et al. Plasma RNA viral load predicts the rate of CD4 T cell decline and death in HIV-2-infected patients in West Africa. AIDS. 2000;14(4):339–44. doi: 10.1097/00002030-200003100-00006. [DOI] [PubMed] [Google Scholar]
- 11.Gottlieb GS, Sow PS, Hawes SE, Ndoye I, Redman M, Coll-Seck AM, et al. Equal plasma viral loads predict a similar rate of CD4+ T cell decline in human immunodeficiency virus (HIV) type 1- and HIV-2-infected individuals from Senegal, West Africa. The Journal of infectious diseases. 2002;185(7):905–14. doi: 10.1086/339295. [DOI] [PubMed] [Google Scholar]
- 12.Evans LA, Moreau J, Odehouri K, Seto D, Thomson-Honnebier G, Legg H, et al. Simultaneous isolation of HIV-1 and HIV-2 from an AIDS patient. Lancet. 1988;2(8625):1389–91. doi: 10.1016/s0140-6736(88)90586-7. [DOI] [PubMed] [Google Scholar]
- 13.Gottlieb GS, Sow PS, Hawes SE, Ndoye I, Coll-Seck AM, Curlin ME, et al. Molecular epidemiology of dual HIV-1/HIV-2 seropositive adults from Senegal, West Africa. AIDS research and human retroviruses. 2003;19(7):575–84. doi: 10.1089/088922203322230941. [DOI] [PubMed] [Google Scholar]
- 14.Honge BL, Jespersen S, Aunsborg J, Mendes DV, Medina C, da Silva Te D, et al. High prevalence and excess mortality of late presenters among HIV-1, HIV-2 and HIV-1/2 dually infected patients in Guinea-Bissau - a cohort study from West Africa. The Pan African medical journal. 2016;25:40. doi: 10.11604/pamj.2016.25.40.8329. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antirectorviral agents in HIV-1-infected adults and adolescents. [accessed on July 28, 2016];Department of Health and Human Services. 2016 Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Section.
- 16.U.S. Food and Drug Adminstration. Complete List of Donor Screening Assays for Infectious Agents and HIV Diagnostic Assays. https://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/UCM080466#Multiplex_Assays2016.
- 17.Gautheret-Dejean A, Bocobza J, Brunet S, Damond F, Plantier JC, Barin F. Performance of rapid tests for discrimination between HIV-1 and/or HIV-2 infections. Journal of medical virology. 2015;87(12):2061–6. doi: 10.1002/jmv.24282. [DOI] [PubMed] [Google Scholar]
- 18.Ullrich T, Ermantraut E, Schulz T, Steinmetzer K. Competitive reporter monitored amplification (CMA)--quantification of molecular targets by real time monitoring of competitive reporter hybridization. PloS one. 2012;7(4):e35438. doi: 10.1371/journal.pone.0035438. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Jani IV, Meggi B, Mabunda N, Vubil A, Sitoe NE, Tobaiwa O, et al. Accurate early infant HIV diagnosis in primary health clinics using a point-of-care nucleic acid test. J Acquir Immune Defic Syndr. 2014;67(1):e1–4. doi: 10.1097/QAI.0000000000000250. [DOI] [PubMed] [Google Scholar]
- 20.Hsiao NY, Dunning L, Kroon M, Myer L. Laboratory Evaluation of the Alere q Point-of-Care System for Early Infant HIV Diagnosis. PloS one. 2016;11(3):e0152672. doi: 10.1371/journal.pone.0152672. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Gottlieb GS, Badiane NM, Hawes SE, Fortes L, Toure M, Ndour CT, et al. Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2009;48(4):476–83. doi: 10.1086/596504. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Gottlieb GS, Smith RA, Dia Badiane NM, Ba S, Hawes SE, Toure M, et al. HIV-2 Integrase Variation in Integrase Inhibitor-Naive Adults in Senegal, West Africa. PloS one. 2011;6(7):e22204. doi: 10.1371/journal.pone.0022204. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Raugi DN, Gottlieb GS, Sow PS, Toure M, Sall F, Gaye A, et al. HIV-1 outcompetes HIV-2 in dually infected Senegalese individuals with low CD4(+) cell counts. AIDS. 2013;27(15):2441–50. doi: 10.1097/QAD.0b013e328362e856. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Chang M, Gottlieb GS, Dragavon JA, Cherne SL, Kenney DL, Hawes SE, et al. Validation for clinical use of a novel HIV-2 plasma RNA viral load assay using the Abbott m2000 platform. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2012;55(2):128–33. doi: 10.1016/j.jcv.2012.06.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Branson B, Owen S, Wesolowski L, Bennett B, Werner B, Wroblewski K, et al. Laboratory testing for the diagnosis of HIV infection: updated recommendations. 2014 http://wwwcdcgov/hiv/pdf/hivtestingalgorithmrecommendation-finalpdf.
- 26.Templer SP, Seiverth B, Baum P, Stevens W, Seguin-Devaux C, Carmona S. Improved Sensitivity of a Dual-Target HIV-1 Qualitative Test for Plasma and Dried Blood Spots. Journal of clinical microbiology. 2016;54(7):1877–82. doi: 10.1128/JCM.00128-16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Tanriverdi S, Chen L, Chen S. A rapid and automated sample-to-result HIV load test for near-patient application. The Journal of infectious diseases. 2010;201(Suppl 1):S52–8. doi: 10.1086/650387. [DOI] [PubMed] [Google Scholar]
- 28.Scott L, Gous N, Carmona S, Stevens W. Laboratory evaluation of the Liat HIV Quant (IQuum) whole-blood and plasma HIV-1 viral load assays for point-of-care testing in South Africa. Journal of clinical microbiology. 2015;53(5):1616–21. doi: 10.1128/JCM.03325-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Issa Sabi HM, Jimson Mgaya, Otto Geisenberger, John France, Michael Hoelscher, Arne Kroidl. Evaluation of maternal and infant HIV point-of-care diagnostics at birth in Tanzania. Conference on Retroviruses and Opportunistic Infections; February 2017; Seattle, Washington. 2017. [Google Scholar]
- 30.Maryanne R, Ibrahim SM, Terence Mohammed, Kenneth Maswabi, Gbolahan Ajibola, Rebecca Gelman, Chloe Auletta-Young, Shahin Lockman, Joseph Makhema, Roger L Shapiro. Evaluation of the Cepheid HIV-1 Qual Point-Of-Care Test for HIV Diagnosis at Birth. Conference on retroviruses and opportunistic infections; February 2017; Seattle, Washington. 2017. [Google Scholar]
- 31.Chang M, Wong AJ, Raugi DN, Smith RA, Seilie AM, Ortega JP, et al. Clinical validation of a novel diagnostic HIV-2 total nucleic acid qualitative assay using the Abbott m2000 platform: Implications for complementary HIV-2 nucleic acid testing for the CDC 4th generation HIV diagnostic testing algorithm. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2017;86:56–61. doi: 10.1016/j.jcv.2016.11.011. [DOI] [PMC free article] [PubMed] [Google Scholar]