Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 36 Records) |
Query Trace: Parekh BS[original query] |
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Risk factors for recent HIV infections among adults in 14 countries in Africa identified by population-based HIV impact assessment surveys, 2015-2019
Currie DW , West CA , Patel HK , Favaloro J , Asiimwe F , Ndagije F , Silver R , Mugurungi O , Shang J , Ndongmo CB , Williams DB , Dzinotyiweyi E , Waruru A , Pasipamire M , Nuwagaba-Biribonwoha H , Dlamini S , McLeod N , Kayirangwa E , Rwibasira G , Minchella PA , Auld AF , Nyirenda R , Getaneh Y , Hailemariam AH , Tondoh-Koui I , Kohemun N , Mgomella GS , Njau PF , Kirungi WL , Dalhatu I , Stafford KA , Bodika SM , Ussery F , McCracken S , Stupp P , Brown K , Duong YT , Parekh BS , Voetsch AC . Emerg Infect Dis 2023 29 (11) 2325-2334 Identifying persons who have newly acquired HIV infections is critical for characterizing the HIV epidemic direction. We analyzed pooled data from nationally representative Population-Based HIV Impact Assessment surveys conducted across 14 countries in Africa for recent infection risk factors. We included adults 15-49 years of age who had sex during the previous year and used a recent infection testing algorithm to distinguish recent from long-term infections. We collected risk factor information via participant interviews and assessed correlates of recent infection using multinomial logistic regression, incorporating each survey's complex sampling design. Compared with HIV-negative persons, persons with higher odds of recent HIV infection were women, were divorced/separated/widowed, had multiple recent sex partners, had a recent HIV-positive sex partner or one with unknown status, and lived in communities with higher HIV viremia prevalence. Prevention programs focusing on persons at higher risk for HIV and their sexual partners will contribute to reducing HIV incidence. |
Point of care CD4 testing in national household surveys - results and quality indicators from eleven population-based HIV impact assessment (PHIA) surveys
Birhanu S , Winterhalter FS , Stupp P , Cates M , Rottinghaus E , Yavo D , Wray-Gordon F , Lupoli K , Ndongmo CB , Longwe H , Reid GA , Metz M , Saito S , McCracken S , Brown K , Voetsch AC , Duong YT , Parekh BS , Patel HK . Microbiol Spectr 2023 11 (3) e0314822 Population-based HIV Impact Assessments (PHIAs) are national household (HH) surveys that provide HIV diagnosis and CD4 testing with an immediate return of results. Accurate CD4 results improve HIV-positive participants' clinical care and inform the effectiveness of HIV programs. Here, we present CD4 results from the PHIA surveys that were conducted in 11 countries in sub-Saharan Africa between 2015 and 2018. All of the HIV-positive participants and 2 to 5% of the HIV-negative participants were offered Pima CD4 (Abbott, IL, USA) point-of-care (POC) tests. The quality of the CD4 test was ensured by conducting instrument verification, comprehensive training, quality control, a review of testing errors and an analysis of unweighted CD4 data by HIV status, age, gender, and antiretroviral (ARV) treatment status. Overall, CD4 testing was completed for 23,085 (99.5%) of the 23,209 HIV-positive and 7,329 (2.7%) of the 270,741 negative participants in 11 surveys. The instrument error rate was 11.3% (range, 4.4% to 15.7%). The median CD4 values among HIV-positive and HIV-negative participants (aged 15+) were 468 cells/mm(3) (interquartile range [IQR], 307 to 654) and 811 cells/mm(3) (IQR, 647 to 1,013), respectively (P < 0.0001). Among the HIV-positive participants (aged 15+), those with detectable ARVs had higher CD4 values (508 cells/mm(3)) than those with undetectable ARVs (385.5 cells/mm(3)). Among the HIV-positive participants (aged 15+), 11.4% (2,528/22,253) had a CD4 value of less than 200 cells/mm(3), and approximately half of them (1,225/2,528 = 48.5%) had detectable ARVs, whereas 51.5% (1,303/2,528) had no detectable ARVs. We successfully implemented high quality POC CD4 testing using Pima instruments. Our data come from nationally representative surveys in 11 countries and provide unique insights regarding the CD4 distribution among HIV-positive individuals as well as the baseline CD4 values among HIV-negative individuals. IMPORTANCE The manuscript describes CD4 levels among HIV-positive individuals and baseline CD4 levels among HIV-negative individuals from 11 sub-Saharan countries, thereby highlighting the importance of CD4 markers in the context of the HIV epidemic. Despite increased ARV access in each country, advanced HIV disease (CD4 < 200 cells/mm(3)) persists among approximately 11% of HIV-positive individuals. Therefore, it is important that our findings are shared with the scientific community to assist with similar implementations of point-of-care testing and to conduct a review of HIV programmatic gaps. |
Evaluation of the Nigeria national HIV rapid testing algorithm
Iriemenam NC , Mpamugo A , Ikpeazu A , Okunoye OO , Onokevbagbe E , Bassey OO , Tapdiyel J , Alagi MA , Meribe C , Ahmed ML , Ikwulono G , Aguolu R , Ashefor G , Nzelu C , Ehoche A , Ezra B , Obioha C , Baffa Sule I , Adedokun O , Mba N , Ihekweazu C , Charurat M , Lindsay B , Stafford KA , Ibrahim D , Swaminathan M , Yufenyuy EL , Parekh BS , Adebajo S , Abimiku A , Okoye MI . PLOS Glob Public Health 2022 2 (11) e0001077 Human Immunodeficiency Virus (HIV) diagnosis remains the gateway to HIV care and treatment. However, due to changes in HIV prevalence and testing coverage across different geopolitical zones, it is crucial to evaluate the national HIV testing algorithm as false positivity due to low prevalence could be detrimental to both the client and the service delivery. Therefore, we evaluated the performance of the national HIV rapid testing algorithm using specimens collected from multiple HIV testing services (HTS) sites and compared the results from different HIV prevalence levels across the six geopolitical zones of Nigeria. The evaluation employed a dual approach, retrospective, and prospective. The retrospective evaluation focused on a desktop review of program data (n = 492,880) collated from patients attending routine HTS from six geopolitical zones of Nigeria between January 2017 and December 2019. The prospective component utilized samples (n = 2,895) collected from the field at the HTS and tested using the current national serial HIV rapid testing algorithm. These samples were transported to the National Reference Laboratory (NRL), Abuja, and were re-tested using the national HIV rapid testing algorithm and HIV-1/2 supplementary assays (Geenius to confirm positives and resolve discordance and multiplex assay). The retrospective component of the study revealed that the overall proportion of HIV positives, based on the selected areas, was 5.7% (28,319/492,880) within the study period, and the discordant rate between tests 1 and 2 was 1.1%. The prospective component of the study indicated no significant differences between the test performed at the field using the national HIV rapid testing algorithm and the re-testing performed at the NRL. The comparison between the test performed at the field using the national HIV rapid testing algorithm and Geenius HIV-1/2 supplementary assay showed an agreement rate of 95.2%, while that of the NRL was 99.3%. In addition, the comparison of the field results with HIV multiplex assay indicated a sensitivity of 96.6%, the specificity of 98.2%, PPV of 97.0%, and Kappa Statistic of 0.95, and that of the NRL with HIV multiplex assay was 99.2%, 99.4%, 99.0%, and 0.99, respectively. Results show that the Nigeria national serial HIV rapid testing algorithm performed very well across the target settings. However, the algorithm's performance in the field was lower than the performance outcomes under a controlled environment in the NRL. There is a need to target testers in the field for routine continuous quality improvement implementation, including refresher trainings as necessary. |
Improving biomarker-based HIV incidence estimation in the treatment era
Fellows IE , Hladik W , Eaton JW , Voetsch AC , Parekh BS , Shiraishi RW . Epidemiology 2023 34 (3) 353-364 BACKGROUND: Estimating HIV-1 incidence using biomarker assays in cross-sectional surveys is important for understanding the HIV pandemic. However, the utility of these estimates has been limited by uncertainty about what input parameters to use for false recency rate (FRR) and mean duration of recent infection (MDRI) after applying a recent infection testing algorithm (RITA). METHODS: This article shows how testing and diagnosis reduce both FRR and mean duration of recent infection compared to a treatment-naive population. A new method is proposed for calculating appropriate context-specific estimates of FRR and mean duration of recent infection. The result of this is a new formula for incidence that depends only on reference FRR and mean duration of recent infection parameters derived in an undiagnosed, treatment-naive, nonelite controller, non-AIDS-progressed population. RESULTS: Applying the methodology to eleven cross-sectional surveys in Africa results in good agreement with previous incidence estimates, except in 2 countries with very high reported testing rates. CONCLUSIONS: Incidence estimation equations can be adapted to account for the dynamics of treatment and recent infection testing algorithms. This provides a rigorous mathematical foundation for the application of HIV recency assays in cross-sectional surveys. |
Estimation of HIV-1 incidence using a testing history-based method; analysis from the population-based HIV impact assessment survey data in 12 African countries
Gurley SA , Stupp PW , Fellows IE , Parekh BS , Young PW , Shiraishi RW , Sullivan PS , Voetsch AC . J Acquir Immune Defic Syndr 2023 92 (3) 189-196 BACKGROUND: Estimating HIV incidence is essential to monitoring progress in sub-Saharan African nations toward global epidemic control. One method for incidence estimation is to test nationally representative samples using laboratory-based incidence assays. An alternative method based on reported HIV testing history and the proportion of undiagnosed infections has recently been described. METHODS: We applied an HIV incidence estimation method which uses history of testing to nationally representative cross-sectional survey data from 12 sub-Saharan African nations with varying country-specific HIV prevalence. We compared these estimates with those derived from laboratory-based incidence assays. Participants were tested for HIV using the national rapid test algorithm and asked about prior HIV testing, date and result of their most recent test, and date of antiretroviral therapy initiation. RESULTS: The testing history-based method consistently produced results that are comparable and strongly correlated with estimates produced using a laboratory-based HIV incidence assay (ρ = 0.85). The testing history-based method produced incidence estimates that were more precise compared with the biomarker-based method. The testing history-based method identified sex-, age-, and geographic location-specific differences in incidence that were not detected using the biomarker-based method. CONCLUSIONS: The testing history-based method estimates are more precise and can produce age-specific and sex-specific incidence estimates that are informative for programmatic decisions. The method also allows for comparisons of the HIV transmission rate and other components of HIV incidence among and within countries. The testing history-based method is a useful tool for estimating and validating HIV incidence from cross-sectional survey data. |
A stable dried tube specimen for quality assurance and training programs for HIV rapid test for recent infection
Di Germanio C , Yufenyuy EL , Hampton DC , Thorbrogger C , Parekh BS , Norris PJ . Microbiol Spectr 2023 11 (1) e0339822 The HIV epidemic is still one of the world's most serious public health challenges, affecting about 38 million people worldwide, especially in sub-Saharan African and Southeast Asian countries. In recent years, tests have been developed to discriminate recent from long-term infection in HIV-infected populations, and these tools can help identify new outbreaks and networks of transmission and target prevention and treatment plans. New rapid tests for recent infection are being deployed in point-of-care settings; however, quality assurance programs need to be implemented to ensure consistency and reliability of the results. We have developed a dried tube specimen (DTS) stabilized with disaccharide trehalose as a quality control reagent for rapid recency testing that can be stored unrefrigerated prior to reconstitution at temperatures up to 37°C for up to 12 weeks. Analysis of 10 trehalose-stabilized DTSs showed that they maintained the same recency classification in all of the samples stored at 4°C and 37°C up to 12 weeks and at 56°C for 2 weeks, while the DTSs prepared without trehalose changed their classification from long-term to recent or recent to negative after storage at 37°C for 12 weeks. Development of DTS quality control reagents will facilitate proficiency and training programs, particularly in settings without cold chain capability in field environments. IMPORTANCE Implementation of stabilized dried tube specimens (DTSs) for quality control and training would facilitate HIV recency programs, especially in point-of-care settings without cold chain availability. This study shows that addition of the disaccharide trehalose to DTSs prior to drying the samples increased stability of the samples across a range of temperatures. This finding provides an affordable way to increase the availability of these key reagents for quality control in resource-constrained settings. |
Performance evaluation of the Asante Rapid Recency Assay for verification of HIV diagnosis and detection of recent HIV-1 infections: implications for epidemic control
Yufenyuy EL , Detorio M , Dobbs T , Patel HK , Jackson K , Shanmugam Vedapuri , Parekh BS . PLoS Glob Public Health 2022 2 (4) e0000316 We previously described development of a rapid test for recent infection (RTRI) that can diagnose HIV infection and detect HIV-1 recent infections in a single device. This technology was transferred to a commercial partner as Asante Rapid Recency Assay (ARRA). We evaluated performance of the ARRA kits in the laboratory using a well-characterized panel of specimens. The plasma specimen panel (N=1500) included HIV-1 (N=570), HIV-2 (N=10), and HIV-negatives (N=920) representing multiple subtypes and geographic locations. Reference diagnostic data were generated using the Bio-Rad HIV-1-2-O EIA/Western blot algorithm with further serotyping performed using the Multispot HIV-1/2 assay. The LAg-Avidity EIA was used to generate reference data on recent and long-term infection for HIV-1 positive specimens at a normalized optical density (ODn) cutoff of 2.0 corresponding to a mean duration of about 6 months. All specimens were tested with ARRA according to the manufacturer's recommendations. Test strips were also read for line intensities using a reader and results were correlated with visual interpretation. ARRA's positive verification line (PVL) correctly classified 575 of 580 HIV-positive and 910 of 920 negative specimens resulting in a sensitivity of 99.1% (95% CI: 98.0-99.6) and specificity of 98.9% (95% CI: 98.1-99.4), respectively. The reader-based classification was similar for PVL with sensitivity of 99.3% (576/580) and specificity of 98.8% (909/920). ARRA's long-term line (LTL) classified 109 of 565 HIV-1 specimens as recent and 456 as long-term compared to 98 as recent and 467 as long-term (LT) by LAg-Avidity EIA (cutoff ODn=2.0), suggesting a mean duration of recent infection (MDRI) close to 6 months. Agreement of ARRA with LAg recent cases was 81.6% (80/98) and LT cases was 93.8% (438/467), with an overall agreement of 91.7% (kappa=0.72). The reader (cutoff 2.9) classified 109/566 specimens as recent infections compared to 99 by the LAg-Avidity EIA for recency agreement of 81.8% (81/99), LT agreement of 9% (439/467) with overall agreement of 91.9% (kappa=0.72). The agreement between visual interpretation and strip reader was 99.9% (95% CI: 99.6-99.9) for the PVL and 98.1% (95% CI: 96.6-98.9) for the LTL. ARRA performed well with HIV diagnostic sensitivity >99% and specificity >98%. Its ability to identify recent infections is comparable to the LA-Avidity EIA corresponding to an MDRI of about 6 months. This point-of-care assay has implications for real-time surveillance of new infections among newly diagnosed individuals for targeted prevention and interrupting ongoing transmission thus accelerating epidemic control. |
Development of a Bead-Based Multiplex Assay for Use in Multianalyte Screening and Surveillance of HIV, Viral Hepatitis, Syphilis, and Herpes.
Yufenyuy EL , Vedapuri S , Zheng A , Cooley G , Danavall D , Mayur S , Kodani M , Chen C , Tun Y , Fakile YF , Martin D , Kamili S , Karem K , Parekh BS . J Clin Microbiol 2022 60 (5) e0234821 Diagnostic assays that can simultaneously determine the presence of infection with multiple pathogens are key for diagnosis and surveillance. Current multiplex diagnostic assays are complex and often have limited availability. We developed a simple, multianalyte, pathogen detection assay for screening and serosurveillance using the Luminex Magpix platform that is high throughput and can be helpful in monitoring multiple diseases. The Luminex bead-based 10-plex immunoassay for the detection of HIV-1, HIV-2, Treponema pallidum, hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus 1 (HSV-1), and HSV-2 infections was accomplished by coupling beads with specific antigens to detect IgG antibodies in plasma or serum samples. Each coupled antigen was systematically optimized, and the performance was evaluated using a panel of well-characterized specimens (n=417) that contained antibodies to HIV-1, HIV-2, T. pallidum, HBV, HCV, HSV-1, and HSV-2. The multiplex assay had a sensitivity of 92.2% (95% Clopper-Pearson confidence interval [CI], 90.2 to 94.0%) and a specificity of 98.1% (95% CI, 97.6 to 98.7%). The sensitivities and specificities for disease-specific biomarker detection ranged from 68.7 to 100% and 95.6 to 100%, respectively. The results showed that the 10-plex immunoassay had an overall agreement of 96.7% (95% CI, 96.7 to 97.3%) with reference tests and a corresponding kappa value of 0.91 (95% CI, 0.90 to 0.93). Kappa values for the individual pathogens ranged from 0.69 to 1.00. The assay is robust and allows the simultaneous detection of antibodies to multiple antigens using a small sample volume in a high-throughput format. This assay has the potential to simplify disease surveillance by providing an alternative to expensive and highly specialized individual tests. |
Geospatial transmission hotspots of recent HIV infection - Malawi, October 2019-March 2020
Telford CT , Tessema Z , Msukwa M , Arons MM , Theu J , Bangara FF , Ernst A , Welty S , O'Malley G , Dobbs T , Shanmugam V , Kabaghe A , Dale H , Wadonda-Kabondo N , Gugsa S , Kim A , Bello G , Eaton JW , Jahn A , Nyirenda R , Parekh BS , Shiraishi RW , Kim E , Tobias JL , Curran KG , Payne D , Auld AF . MMWR Morb Mortal Wkly Rep 2022 71 (9) 329-334 Persons infected with HIV are more likely to transmit the virus during the early stages (acute and recent) of infection, when viral load is elevated and opportunities to implement risk reduction are limited because persons are typically unaware of their status (1,2). Identifying recent HIV infections (acquired within the preceding 12 months)* is critical to understanding the factors and geographic areas associated with transmission to strengthen program intervention, including treatment and prevention (2). During June 2019, a novel recent infection surveillance initiative was integrated into routine HIV testing services in Malawi, a landlocked country in southeastern Africa with one of the world's highest prevalences of HIV infection.(†) The objectives of this initiative were to collect data on new HIV diagnoses, characterize the epidemic, and guide public health response (2). New HIV diagnoses were classified as recent infections based on a testing algorithm that included results from the rapid test for recent infection (RTRI)(§) and HIV viral load testing (3,4). Among 9,168 persons aged ≥15 years with a new HIV diagnosis who received testing across 103 facilities during October 2019-March 2020, a total of 304 (3.3%) were classified as having a recent infection. Higher proportions of recent infections were detected among females, persons aged <30 years, and clients at maternal and child health and youth clinics. Using a software application that analyzes clustering in spatially referenced data, transmission hotspots were identified with rates of recent infection that were significantly higher than expected. These near real-time HIV surveillance data highlighted locations across Malawi, allowing HIV program stakeholders to assess program gaps and improve access to HIV testing, prevention, and treatment services. Hotspot investigation information could be used to tailor HIV testing, prevention, and treatment to ultimately interrupt transmission. |
Performance of a novel rapid test for recent HIV infection among newly-diagnosed pregnant adolescent girls and young women in four high-HIV-prevalence districts-Malawi, 2017-2018
Agyemang EA , Kim AA , Dobbs T , Zungu I , Payne D , Maher AD , Curran K , Kim E , Kwalira H , Limula H , Adhikari A , Welty S , Kandulu J , Nyirenda R , Auld AF , Rutherford GW , Parekh BS . PLoS One 2022 17 (2) e0262071 Tests for recent HIV infection (TRI) distinguish recent from long-term HIV infections using markers of antibody maturation. The limiting antigen avidity enzyme immunoassay (LAg EIA) is widely used with HIV viral load (VL) in a recent infection testing algorithm (RITA) to improve classification of recent infection status, estimate population-level HIV incidence, and monitor trends in HIV transmission. A novel rapid test for recent HIV infection (RTRI), Asanté™, can determine HIV serostatus and HIV recency within minutes on a lateral flow device through visual assessment of test strip or reader device. We conducted a field-based laboratory evaluation of the RTRI among pregnant adolescent girls and young women (AGYW) attending antenatal clinics (ANC) in Malawi.We enrolled pregnant AGYW aged <25 years testing HIV-positive for the first time at their first ANC visit from 121 ANCs in four high-HIV burden districts. Consenting participants provided blood for recency testing using LAg EIA and RTRI, which were tested in central laboratories. Specimens with LAg EIA normalized optical density values ≤2.0 were classified as probable recent infections. RTRI results were based on: (1) visual assessment: presence of a long-term line (LT) indicating non-recent infection and absence of the line indicating recent infection; or (2) a reader; specimens with LT line intensity units <3.0 were classified as probable recent infections. VL was measured for specimens classified as a probable recent infections by either assay; those with HIV-1 RNA ≥1,000 copies/mL were classified as confirmed recent infections. We evaluated the performance of the RTRI by calculating correlation between RTRI and LAg EIA results, and percent agreement and kappa between RTRI and LAg EIA RITA results.Between November 2017 to June 2018, 380 specimens were available for RTRI evaluation; 376 (98.9%) were confirmed HIV-positive on RTRI. Spearman's rho between RTRI and LAg EIA was 0.72 indicating strong correlation. Percent agreement and kappa between RTRI- and LAg EIA-based RITAs were >90% and >0.65 respectively indicating substantial agreement between the RITAs.This was the first field evaluation of an RTRI in sub-Saharan Africa, which demonstrated good performance of the assay and feasibility of integrating RTRI into routine HIV testing services for real-time surveillance of recent HIV infection. |
HIV incidence, viremia, and the national response in Eswatini: Two sequential population-based surveys
Nkambule R , Philip NM , Reid G , Mnisi Z , Nuwagaba-Biribonwoha H , Ao TT , Ginindza C , Duong YT , Patel H , Saito S , Solmo C , Brown K , Moore CS , Voetsch AC , Bicego G , Bock N , Mhlanga F , Dlamini T , Mabuza K , Zwane A , Sahabo R , Dobbs T , Parekh BS , El-Sadr W , Ryan C , Justman J . PLoS One 2021 16 (12) e0260892 With the highest HIV incidence and prevalence globally, the government of Eswatini started a substantial scale-up of HIV treatment and prevention services in 2011. Two sequential large population-based surveys were conducted before and after service expansion to assess the impact of the national response. Cross-sectional, household-based, nationally representative samples of adults, ages 18 to 49 years, were sampled in 2011 and 2016. We measured HIV prevalence, incidence (recent infection based on limiting antigen ≤1.5 optical density units and HIV RNA ≥1000 copies/mL), viral load suppression (HIV RNA <1000 copies/mL among all seropositive adults) and unsuppressed viremia (HIV RNA ≥1000 copies/mL among all, regardless of HIV status) and assessed for temporal changes by conducting a trend analysis of the log ratio of proportions, using a Z statistic distribution. HIV prevalence remained stable from 2011 to 2016 [32% versus 30%, p = 0.10]. HIV incidence significantly declined 48% [2.48% versus 1.30%, p = 0.01]. Incidence remained higher among women than men [2011: 3.16% versus 1.83%; 2016: 1.76% versus 0.86%], with a smaller but significant relative reduction among women [44%; p = 0.04] than men [53%; p = 0.09]. The proportion of seropositive adults with viral load suppression significantly increased from 35% to 71% [p < .001]. The proportion of the total adult population with unsuppressed viremia decreased from 21% to 9% [p < .001]. National HIV incidence in Eswatini decreased by nearly half and viral load suppression doubled over a five-year period. Unsuppressed viremia in the total population decreased 58%. These population-based findings demonstrate the national impact of expanded HIV services in a hyperendemic country. |
Progress toward the 90-90-90 HIV targets in Zimbabwe and identifying those left behind
Hakim AJ , Tippett Barr BA , Kinchen S , Musuka G , Manjengwa J , Munyati S , Gwanzura L , Mugurungi O , Ncube G , Saito S , Parekh BS , Patel H , Duong YT , Gonese E , Sleeman K , Ruangtragool L , Justman J , Herman-Roloff A , Radin E . J Acquir Immune Defic Syndr 2021 88 (3) 272-281 OBJECTIVE: We present findings from the nationally representative Zimbabwe Population-based HIV Impact Assessment (ZIMPHIA) that characterize Zimbabwe's progress toward the Joint United Nations Programme on HIV/AIDS 90-90-90 targets. DESIGN: We conducted a cross-sectional household survey. METHODS: Consenting adults and children in the household were eligible to participate in ZIMPHIA (October 2015-August 2016). Participants completed face-to-face interviews and provided blood for HIV, CD4, viral load, and syphilis testing. VLS was defined as HIV RNA <1,000 copies/mL. HIV-positive specimens were tested for the presence of selected antiretroviral drugs. Data were weighted. Analysis was restricted to HIV-positive adults aged 15-64 years. RESULTS: We enrolled 11,098 men and 14,033 women aged 15-64 years. HIV prevalence was 14.1%. Of those living with HIV, 76.8% (95% confidence interval [CI]: 74.9-78.7) were aware of their HIV status or had detectable antiretroviral levels. Of these, 88.4% (95% CI: 87.1-89.7) were receiving ART, and of these people, 85.3% (95% CI: 83.4-87.1) had VLS. Male sex age 15-34 years and having one or more sexual partners were associated with being unaware of one's HIV-positive status. Age <50 years and not taking cotrimoxazole were associated with being less likely to be being both aware and taking ART. Male sex, age <50 years, and taking cotrimoxazole were associated with being on ART but not having VLS. CONCLUSIONS: Zimbabwe has made great strides toward epidemic control. Focusing resources on case finding, particularly among men, people aged<35 years, and sexually active individuals can help Zimbabwe attain 90-90-90 targets. |
Successful Use of Near Point-of-Care Early Infant Diagnosis in NAMPHIA to Improve Turnaround Times in a National Household Survey
Domaoal RA , Sleeman K , Sawadogo S , Dzinamarira T , Frans N , Shatumbu SP , Kakoma LN , Shuumbwa TK , Cox MH , Stephens S , Nisbet L , Metz M , Saito S , Williams DB , Voetsch AC , Patel HK , Parekh BS , Duong YT . J Acquir Immune Defic Syndr 2021 87 S67-s72 BACKGROUND: In the population-based HIV impact assessment surveys, early infant diagnosis (EID) was provided to infants <18 months without a prior diagnosis. For the Namibia population-based HIV impact assessment (NAMPHIA), the GeneXpert platform was assessed for the feasibility of near POC EID testing compared with the standard Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) platform. Quality assurance measures and turnaround time were compared to improve EID results reporting. METHODS: NAMPHIA participants were screened for HIV exposure using Determine HIV-1/2 rapid test; samples reactive on Determine received EID testing on the GeneXpert instrument and Xpert HIV-1 Qual assay using whole blood. Results were confirmed at the Namibia Institute of Pathology using dried blood spots on the Roche CAP/CTM platform per national guidelines. RESULTS: Of the 762 screened infants, 61 (8.0%) were Determine-reactive and considered HIV-exposed. Of the 61 exposed infants, 2 were found to be HIV-infected whereas 59 were negative on both GeneXpert and Roche platforms, achieving 100% concordance. Average turnaround time was 3.4 days for the Xpert HIV-1 Qual assay, and average time from collection to testing was 1.0 days for GeneXpert compared with 10.7 days for Roche. No samples failed using GeneXpert whereas 1 sample failed using Roche and was repeated. CONCLUSION: Quality POC EID testing is feasible in a national survey through extensive training and external quality assurance measures. The use of decentralized POC EID for national testing would provide rapid diagnosis and improve TATs which may prevent loss to follow-up, ensure linkage to care, and improve clinical outcomes for infants. |
A Comprehensive Approach to Assuring Quality of Laboratory Testing in HIV Surveys: Lessons Learned From the Population-Based HIV Impact Assessment Project
Patel HK , Duong YT , Birhanu S , Dobbs T , Lupoli K , Moore C , Detorio M , Sleeman K , Manjengwa J , Wray-Gordon F , Yavo D , Jackson K , Domaoal RA , Yufenyuy EL , Vedapuri S , Ndongmo CB , Ogollah FM , Dzinamarira T , Rubinstein P , Sachathep KK , Metz M , Longwe H , Saito S , Brown K , Voetsch AC , Parekh BS . J Acquir Immune Defic Syndr 2021 87 S17-s27 BACKGROUND: Conducting HIV surveys in resource-limited settings is challenging because of logistics, limited availability of trained personnel, and complexity of testing. We described the procedures and systems deemed critical to ensure high-quality laboratory data in the population-based HIV impact assessments and large-scale household surveys. METHODS: Laboratory professionals were engaged in every stage of the surveys, including protocol development, site assessments, procurement, training, quality assurance, monitoring, analysis, and reporting writing. A tiered network of household, satellite laboratories, and central laboratories, accompanied with trainings, optimized process for blood specimen collection, storage, transport, and real-time monitoring of specimen quality, and test results at each level proved critical in maintaining specimen integrity and high-quality testing. A plausibility review of aggregate merged data was conducted to confirm associations between key variables as a final quality check for quality of laboratory results. RESULTS: Overall, we conducted a hands-on training for 3355 survey staff across 13 surveys, with 160-387 personnel trained per survey on biomarker processes. Extensive training and monitoring demonstrated that overall, 99% of specimens had adequate volume and 99.8% had no hemolysis, indicating high quality. We implemented quality control and proficiency testing for testing, resolved discrepancies, verified >300 Pima CD4 instruments, and monitored user errors. Aggregate data review for plausibility further confirmed the high quality of testing. CONCLUSIONS: Ongoing engagement of laboratory personnel to oversee processes at all levels of the surveys is critical for successful national surveys. High-quality population-based HIV impact assessments laboratory data ensured reliable results and demonstrated the impact of HIV programs in 13 countries. |
HIV-1 Recent Infection Testing Algorithm With Antiretroviral Drug Detection to Improve Accuracy of Incidence Estimates
Voetsch AC , Duong YT , Stupp P , Saito S , McCracken S , Dobbs T , Winterhalter FS , Williams DB , Mengistu A , Mugurungi O , Chikwanda P , Musuka G , Ndongmo CB , Dlamini S , Nuwagaba-Biribonwoha H , Pasipamire M , Tegbaru B , Eshetu F , Biraro S , Ward J , Aibo D , Kabala A , Mgomella GS , Malewo O , Mushi J , Payne D , Mengistu Y , Asiimwe F , Shang JD , Dokubo EK , Eno LT , Zoung-Kanyi Bissek AC , Kingwara L , Junghae M , Kiiru JN , Mwesigwa RCN , Balachandra S , Lobognon R , Kampira E , Detorio M , Yufenyuy EL , Brown K , Patel HK , Parekh BS . J Acquir Immune Defic Syndr 2021 87 S73-s80 BACKGROUND: HIV-1 incidence calculation currently includes recency classification by HIV-1 incidence assay and unsuppressed viral load (VL ≥ 1000 copies/mL) in a recent infection testing algorithm (RITA). However, persons with recent classification not virally suppressed and taking antiretroviral (ARV) medication may be misclassified. SETTING: We used data from 13 African household surveys to describe the impact of an ARV-adjusted RITA on HIV-1 incidence estimates. METHODS: HIV-seropositive samples were tested for recency using the HIV-1 Limiting Antigen (LAg)-Avidity enzyme immunoassay, HIV-1 viral load, ARVs used in each country, and ARV drug resistance. LAg-recent result was defined as normalized optical density values ≤1.5. We compared HIV-1 incidence estimates using 2 RITA: RITA1: LAg-recent + VL ≥ 1000 copies/mL and RITA2: RITA1 + undetectable ARV. We explored RITA2 with self-reported ARV use and with clinical history. RESULTS: Overall, 357 adult HIV-positive participants were classified as having recent infection with RITA1. RITA2 reclassified 55 (15.4%) persons with detectable ARV as having long-term infection. Those with detectable ARV were significantly more likely to be aware of their HIV-positive status (84% vs. 10%) and had higher levels of drug resistance (74% vs. 26%) than those without detectable ARV. RITA2 incidence was lower than RITA1 incidence (range, 0%-30% decrease), resulting in decreased estimated new infections from 390,000 to 341,000 across the 13 countries. Incidence estimates were similar using detectable or self-reported ARV (R2 > 0.995). CONCLUSIONS: Including ARV in RITA2 improved the accuracy of HIV-1 incidence estimates by removing participants with likely long-term HIV infection. |
High level of HIV false positives using EIA-based algorithm in survey: Importance of confirmatory testing
Augusto  DR , Iriemenam NC , Kohatsu L , de Sousa L , Maueia C , Hara C , Mula F , Cuamba G , Chelene I , Langa Z , Lohman N , Faife F , Giles D , Sabonete AJ , Samo Gudo E , Jani I , Parekh BS . PLoS One 2020 15 (10) e0239782 The Mozambique Indicators of Immunization, Malaria and HIV/AIDS (IMASIDA) survey was conducted in 2015 and used a two Enzyme Immunoassay (EIA) (Vironostika HIV-1/2 and Murex HIV-1/2) based algorithm to determine the HIV status of the consented participants. The Mozambique Ministry of Health, with support from the US Centers for Disease Control and Prevention (US CDC), added Bio-Rad Geenius™ HIV-1/2 Supplemental Assay to the IMASIDA HIV testing algorithm to confirm all specimens that were found to be reactive on one or both EIAs. In total 11690 specimens were collected to estimate the proportion of HIV positive samples. Results indicate that the proportion of HIV positive samples based on the concordant positive results of two EIA assays was 21.5% (2518/11690). The addition of the Geenius assay to the IMASIDA HIV testing algorithm demonstrated that 792 (31.5%) of 2518 specimens were false-positive and reduced the proportion of HIV positive samples to 14.7% (1722/11690), demonstrating the importance of including a highly specific HIV test to confirm HIV diagnosis. HIV surveys exclusively based on EIA testing algorithm may result in misleading high prevalence results. Our results demonstrate that more specific confirmatory testing should be added to the EIA-based algorithms to ensure accurate HIV diagnosis and correct HIV prevalence estimate in cross-sectional surveys. |
Tracking with recency assays to control the epidemic: real-time HIV surveillance and public health response
Kim AA , Behel S , Northbrook S , Parekh BS . AIDS 2019 33 (9) 1527-1529 Through 2017, roughly 40 years since HIV/AIDS became a global health crisis, the world has experienced devastating consequences: an estimated 35 million HIV-infected persons have died, 17 million children have been orphaned, and 37 million persons are living with the virus [1,2]. With sustained commitment to address the epidemic, control and virtual elimination of HIV is within reach in some countries. In 2014, the Joint United Nations Programme on HIV/AIDS released ambitious treatment targets to reach HIV epidemic control by 2030, calling for 90% of all persons living with HIV (PLHIV) to be diagnosed, 90% of diagnosed PLHIV to be on HIV treatment, and 90% of treated PLHIV to be virally suppressed by 2020 (90-90-90) [3]. By 2017, 75% of PLHIV knew their HIV status, 79% of these were on treatment, and 81% of these achieved viral suppression [1]. Still millions of PLHIV who require diagnosis and treatment are not yet reached. |
Diagnosis of human immunodeficiency virus infection
Parekh BS , Ou CY , Fonjungo PN , Kalou MB , Rottinghaus E , Puren A , Alexander H , Hurlston Cox M , Nkengasong JN . Clin Microbiol Rev 2019 32 (1) HIV diagnostics have played a central role in the remarkable progress in identifying, staging, initiating, and monitoring infected individuals on life-saving antiretroviral therapy. They are also useful in surveillance and outbreak responses, allowing for assessment of disease burden and identification of vulnerable populations and transmission "hot spots," thus enabling planning, appropriate interventions, and allocation of appropriate funding. HIV diagnostics are critical in achieving epidemic control and require a hybrid of conventional laboratory-based diagnostic tests and new technologies, including point-of-care (POC) testing, to expand coverage, increase access, and positively impact patient management. In this review, we provide (i) a historical perspective on the evolution of HIV diagnostics (serologic and molecular) and their interplay with WHO normative guidelines, (ii) a description of the role of conventional and POC testing within the tiered laboratory diagnostic network, (iii) information on the evaluations and selection of appropriate diagnostics, (iv) a description of the quality management systems needed to ensure reliability of testing, and (v) strategies to increase access while reducing the time to return results to patients. Maintaining the central role of HIV diagnostics in programs requires periodic monitoring and optimization with quality assurance in order to inform adjustments or alignment to achieve epidemic control. |
Returning HIV-1 viral load results to participant-selected health facilities in national Population-based HIV Impact Assessment (PHIA) household surveys in three sub-Saharan African Countries, 2015 to 2016
Saito S , Duong YT , Metz M , Lee K , Patel H , Sleeman K , Manjengwa J , Ogollah FM , Kasongo W , Mitchell R , Mugurungi O , Chimbwandira F , Moyo C , Maliwa V , Mtengo H , Nkumbula T , Ndongmo CB , Vere NS , Chipungu G , Parekh BS , Justman J , Voetsch AC . J Int AIDS Soc 2017 20 Suppl 7 19-25 INTRODUCTION: Logistical complexities of returning laboratory test results to participants have precluded most population-based HIV surveys conducted in sub-Saharan Africa from doing so. For HIV positive participants, this presents a missed opportunity for engagement into clinical care and improvement in health outcomes. The Population-based HIV Impact Assessment (PHIA) surveys, which measure HIV incidence and the prevalence of viral load (VL) suppression in selected African countries, are returning VL results to health facilities specified by each HIV positive participant within eight weeks of collection. We describe the performance of the specimen and data management systems used to return VL results to PHIA participants in Zimbabwe, Malawi and Zambia. METHODS: Consenting participants underwent home-based counseling and HIV rapid testing as per national testing guidelines; all confirmed HIV positive participants had VL measured at a central laboratory on either the Roche CAP/CTM or Abbott m2000 platform. On a bi-weekly basis, a dedicated data management team produced logs linking the VL test result with the participants' contact information and preferred health facility; project staff sent test results confidentially via project drivers, national courier systems, or electronically through an adapted short message service (SMS). Participants who provided cell phone numbers received SMS or phone call alerts regarding availability of VL results. RESULTS AND DISCUSSION: From 29,634 households across the three countries, 78,090 total participants 0 to 64 years in Zimbabwe and Malawi and 0 to 59 years in Zambia underwent blood draw and HIV testing. Of the 8391 total HIV positive participants identified, 8313 (99%) had VL tests performed and 8245 (99%) of these were returned to the selected health facilities. Of the 5979 VL results returned in Zimbabwe and Zambia, 85% were returned within the eight-week goal with a median turnaround time of 48 days (IQR: 33 to 61). In Malawi, where exact return dates were unavailable all 2266 returnable results reached the health facilities by 11 weeks. CONCLUSIONS: The first three PHIA surveys returned the vast majority of VL results to each HIV positive participant's preferred health facility within the eight-week target. Even in the absence of national VL monitoring systems, a system to return VL results from a population-based survey is feasible, but it requires developing laboratory and data management systems and dedicated staff. These are likely important requirements to strengthen return of results systems in routine clinical care. |
Swaziland HIV Incidence Measurement Survey (SHIMS): a prospective national cohort study
Justman J , Reed JB , Bicego G , Donnell D , Li K , Bock N , Koler A , Philip NM , Mlambo CK , Parekh BS , Duong YT , Ellenberger DL , El-Sadr WM , Nkambule R . Lancet HIV 2016 4 (2) e83-e92 BACKGROUND: Swaziland has the highest national HIV prevalence worldwide. The Swaziland HIV Incidence Measurement Survey (SHIMS) provides the first national HIV incidence estimate based on prospectively observed HIV seroconversions. METHODS: A two-stage survey sampling design was used to select a nationally representative sample of men and women aged 18-49 years from 14 891 households in 575 enumeration areas in Swaziland, who underwent household-based counselling and rapid HIV testing during 2011. All individuals aged 18-49 years who resided or had slept in the household the night before and were willing to undergo home-based HIV testing, answer demographic and behavioural questions in English or siSwati, and provide written informed consent were eligible for the study. We performed rapid HIV testing and assessed sociodemographic and behavioural characteristics with use of a questionnaire at baseline and, for HIV-seronegative individuals, 6 months later. We calculated HIV incidence with Poisson regression modelling as events per person-years x 100, and we assessed covariables as predictors with Cox proportional hazards modelling. Survey weighting was applied and all models used survey sampling methods. FINDINGS: Between Dec 10, 2010, and June 25, 2011, 11 897 HIV-seronegative adults were enrolled in SHIMS and 11 232 (94%) were re-tested. Of these, 145 HIV seroconversions were observed, resulting in a weighted HIV incidence of 2.4% (95% CI 2.1-2.8). Incidence was nearly twice as high in women (3.1%; 95% CI 2.6-3.7) as in men (1.7%; 1.3-2.1, p<0.0001). Among men, partner's HIV-positive status (adjusted hazard ratio [aHR] 2.67, 1.06-6.82, p=0.040) or unknown serostatus (aHR 4.64, 2.32-9.27, p<0.0001) in the past 6 months predicted HIV seroconversion. Among women, significant predictors included not being married (aHR 2.90, 1.44-5.84, p=0.0030), having a spouse who lives elsewhere (aHR 2.66, 1.29-5.45, p=0.0078), and having a partner in the past 6 months with unknown HIV status (aHR 2.87, 1.44-5.84, p=0.0030). INTERPRETATION: Swaziland has the highest national HIV incidence in the world. In high-prevalence countries, population-based incidence measures and programmes that further expand HIV testing and support disclosure of HIV status are needed. FUNDING: President's Emergency Plan for AIDS Relief (PEPFAR) by the Centers for Disease Control and Prevention. |
HIV testing and human rights: the right to the right test
Nkengasong JN , Parekh BS , Hader SL . Lancet HIV 2016 3 (10) e457-8 In September, 2015, Stefano Vella published an important commentary in The Lancet HIV on addressing barriers to end the HIV epidemic by 2030.1 An additional barrier that needs to be addressed is to ensure the quality of HIV diagnostic testing as programmes are scaled up. About 150 million children and adults in 129 low-income and middle-income countries reportedly received HIV testing services in 2014.2 Optimistically assuming a 1% error rate (ie, 99% accuracy), a large number of individuals could be wrongly initiated on antiretroviral therapy (ART) as we enter the test-and-treat era while others who need therapy would not receive it. In fact, although diagnostic tests have high sensitivity and specificity, some studies have reported misdiagnosis rates of 2·6–4·8% that occur in HIV testing programme settings.3, 4 | Almost 20 years ago, in 1998, the Office of the High Commissioner for Human Rights (OHCHR) and the Joint UN Programme on HIV/AIDS (UNAIDS) issued the International Guidelines on HIV/AIDS and Human Rights.5 The guidelines emphasised the need for countries to take steps to protect human rights in the context of HIV/AIDS. The epidemic is ever evolving at a rapid pace, and much has happened since the guidelines were adopted: at the time, fewer than 50 000 people with HIV were receiving life-saving ART in developing countries, now more than 17 million are estimated to be on treatment.6 As the global community responds to the prospects of ending the HIV/AIDS epidemic by 2030, UNAIDS has set an ambitious target of 90% of infected individuals being diagnosed, 90% of those being on ART, and 90% of those achieving viral load suppression by 2020.7 |
Identifying risk factors for recent HIV infection in Kenya using a recent infection testing algorithm: Results from a nationally representative population-based survey
Kim AA , Parekh BS , Umuro M , Galgalo T , Bunnell R , Makokha E , Dobbs T , Murithi P , Muraguri N , De Cock KM , Mermin J . PLoS One 2016 11 (5) e0155498 INTRODUCTION: A recent infection testing algorithm (RITA) that can distinguish recent from long-standing HIV infection can be applied to nationally representative population-based surveys to characterize and identify risk factors for recent infection in a country. MATERIALS AND METHODS: We applied a RITA using the Limiting Antigen Avidity Enzyme Immunoassay (LAg) on stored HIV-positive samples from the 2007 Kenya AIDS Indicator Survey. The case definition for recent infection included testing recent on LAg and having no evidence of antiretroviral therapy use. Multivariate analysis was conducted to determine factors associated with recent and long-standing infection compared to HIV-uninfected persons. All estimates were weighted to adjust for sampling probability and nonresponse. RESULTS: Of 1,025 HIV-antibody-positive specimens, 64 (6.2%) met the case definition for recent infection and 961 (93.8%) met the case definition for long-standing infection. Compared to HIV-uninfected individuals, factors associated with higher adjusted odds of recent infection were living in Nairobi (adjusted odds ratio [AOR] 11.37; confidence interval [CI] 2.64-48.87) and Nyanza (AOR 4.55; CI 1.39-14.89) provinces compared to Western province; being widowed (AOR 8.04; CI 1.42-45.50) or currently married (AOR 6.42; CI 1.55-26.58) compared to being never married; having had ≥ 2 sexual partners in the last year (AOR 2.86; CI 1.51-5.41); not using a condom at last sex in the past year (AOR 1.61; CI 1.34-1.93); reporting a sexually transmitted infection (STI) diagnosis or symptoms of STI in the past year (AOR 1.97; CI 1.05-8.37); and being aged <30 years with: 1) HSV-2 infection (AOR 8.84; CI 2.62-29.85), 2) male genital ulcer disease (AOR 8.70; CI 2.36-32.08), or 3) lack of male circumcision (AOR 17.83; CI 2.19-144.90). Compared to HIV-uninfected persons, factors associated with higher adjusted odds of long-standing infection included living in Coast (AOR 1.55; CI 1.04-2.32) and Nyanza (AOR 2.33; CI 1.67-3.25) provinces compared to Western province; being separated/divorced (AOR 1.87; CI 1.16-3.01) or widowed (AOR 2.83; CI 1.78-4.45) compared to being never married; having ever used a condom (AOR 1.61; CI 1.34-1.93); and having a STI diagnosis or symptoms of STI in the past year (AOR 1.89; CI 1.20-2.97). Factors associated with lower adjusted odds of long-standing infection included using a condom at last sex in the past year (AOR 0.47; CI 0.36-0.61), having no HSV2-infection at aged <30 years (AOR 0.38; CI 0.20-0.75) or being an uncircumcised male aged <30 years (AOR 0.30; CI 0.15-0.61). CONCLUSION: We identified factors associated with increased risk of recent and longstanding HIV infection using a RITA applied to blood specimens collected in a nationally representative survey. Though some false-recent cases may have been present in our sample, the correlates of recent infection identified were epidemiologically and biologically plausible. These methods can be used as a model for other countries with similar epidemics to inform targeted combination prevention strategies aimed to drastically decrease new infections in the population. |
Mean Recency Period for Estimation of HIV-1 Incidence with the BED-Capture EIA and Bio-Rad Avidity in Persons Diagnosed in the United States with Subtype B
Hanson DL , Song R , Masciotra S , Hernandez A , Dobbs TL , Parekh BS , Owen SM , Green TA . PLoS One 2016 11 (4) e0152327 HIV incidence estimates are used to monitor HIV-1 infection in the United States. Use of laboratory biomarkers that distinguish recent from longstanding infection to quantify HIV incidence rely on having accurate knowledge of the average time that individuals spend in a transient state of recent infection between seroconversion and reaching a specified biomarker cutoff value. This paper describes five estimation procedures from two general statistical approaches, a survival time approach and an approach that fits binomial models of the probability of being classified as recently infected, as a function of time since seroconversion. We compare these procedures for estimating the mean duration of recent infection (MDRI) for two biomarkers used by the U.S. National HIV Surveillance System for determination of HIV incidence, the Aware BED EIA HIV-1 incidence test (BED) and the avidity-based, modified Bio-Rad HIV-1/HIV-2 plus O ELISA (BRAI) assay. Collectively, 953 specimens from 220 HIV-1 subtype B seroconverters, taken from 5 cohorts, were tested with a biomarker assay. Estimates of MDRI using the non-parametric survival approach were 198.4 days (SD 13.0) for BED and 239.6 days (SD 13.9) for BRAI using cutoff values of 0.8 normalized optical density and 30%, respectively. The probability of remaining in the recent state as a function of time since seroconversion, based upon this revised statistical approach, can be applied in the calculation of annual incidence in the United States. |
Access and quality of HIV-related point of care diagnostic testing in global health programs
Fonjungo PN , Boeras DI , Zeh C , Alexander H , Parekh BS , Nkengasong JN . Clin Infect Dis 2015 62 (3) 369-374 Access to point-of-care testing (POCT) improves patient care, especially in resource-limited settings where laboratory infrastructure is poor and the bulk of the population lives in rural settings. However, because of challenges in rolling out the technology and weak quality assurance measures, the promise of HIV-related POCT in resource-limited settings has not been fully exploited to improve patient care and impact public health. Because of these challenges, the Joint United Nations Programme on HIV/AIDS in partnership with other organizations recently launched the Diagnostics Access Initiative. Expanding HIV programs, including the "test and treat" strategies and the newly established UNAIDS 90-90-90 targets will require increased access to reliable and accurate POC test results. In this review, we examine various components that could improve access and uptake of quality-assured POC tests to ensure coverage and public health impact. These components include evaluation, policy, regulation, and innovative approaches to strengthen the quality of POCT. |
Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes
Duong YT , Kassanjee R , Welte A , Morgan M , De A , Dobbs T , Rottinghaus E , Nkengasong J , Curlin ME , Kittinunvorakoon C , Raengsakulrach B , Martin M , Choopanya K , Vanichseni S , Jiang Y , Qiu M , Yu H , Hao Y , Shah N , Le LV , Kim AA , Nguyen TA , Ampofo W , Parekh BS . PLoS One 2015 10 (2) e0114947 BACKGROUND: Mean duration of recent infection (MDRI) and misclassification of long-term HIV-1 infections, as proportion false recent (PFR), are critical parameters for laboratory-based assays for estimating HIV-1 incidence. Recent review of the data by us and others indicated that MDRI of LAg-Avidity EIA estimated previously required recalibration. We present here results of recalibration efforts using >250 seroconversion panels and multiple statistical methods to ensure accuracy and consensus. METHODS: A total of 2737 longitudinal specimens collected from 259 seroconverting individuals infected with diverse HIV-1 subtypes were tested with the LAg-Avidity EIA as previously described. Data were analyzed for determination of MDRI at ODn cutoffs of 1.0 to 2.0 using 7 statistical approaches and sub-analyzed by HIV-1 subtypes. In addition, 3740 specimens from individuals with infection >1 year, including 488 from patients with AIDS, were tested for PFR at varying cutoffs. RESULTS: Using different statistical methods, MDRI values ranged from 88-94 days at cutoff ODn = 1.0 to 177-183 days at ODn = 2.0. The MDRI values were similar by different methods suggesting coherence of different approaches. Testing for misclassification among long-term infections indicated that overall PFRs were 0.6% to 2.5% at increasing cutoffs of 1.0 to 2.0, respectively. Balancing the need for a longer MDRI and smaller PFR (<2.0%) suggests that a cutoff ODn = 1.5, corresponding to an MDRI of 130 days should be used for cross-sectional application. The MDRI varied among subtypes from 109 days (subtype A&D) to 152 days (subtype C). CONCLUSIONS: Based on the new data and revised analysis, we recommend an ODn cutoff = 1.5 to classify recent and long-term infections, corresponding to an MDRI of 130 days (118-142). Determination of revised parameters for estimation of HIV-1 incidence should facilitate application of the LAg-Avidity EIA for worldwide use. |
Poor performance of the determine HIV-1/2 Ag/Ab combo fourth-generation rapid test for detection of acute infections in a National Household Survey in Swaziland
Duong YT , Mavengere Y , Patel H , Moore C , Manjengwa J , Sibandze D , Rasberry C , Mlambo C , Li Z , Emel L , Bock N , Moore J , Nkambule R , Justman J , Reed J , Bicego G , Ellenberger DL , Nkengasong JN , Parekh BS . J Clin Microbiol 2014 52 (10) 3743-8 Fourth-generation HIV rapid tests (RTs) claim to detect both p24 antigen (Ag) and HIV antibodies (Ab) for early identification of acute infections, important for targeted prevention and reducing HIV transmission. In a nationally representative household survey in Swaziland, 18,172 adults, age 18-49 years, received home-based HIV rapid testing in 2010-2011. Of the 18,172 individuals, 5,822 (32.0%) were Ab+ by Determine HIV-1/2 Ab/Ab Combo and of those, 5,789 (99.4%) were confirmed reactive by Uni-Gold. Determine Combo identified 12 individuals as acute infections (Ag+/Ab-); however, none had detectable HIV-1 RNA and 8 of 12 remained HIV negative at 6-week follow-up visits (4 lost to follow up). All RT non-reactive samples were pooled and tested by nucleic acid amplification testing (NAAT) to identify acute infections. NAAT identified 13 (0.1%) of the 12,338 HIV antibody-negative specimens as HIV RNA positive with RNA levels ranging from 300 to >10,000,000 copies/mL. However, none of them were Ag+ on Determine Combo. Follow-up testing of 12 of the 13 NAAT-positive individuals at 6 months demonstrated 12 seroconversions (1 lost to follow-up). Therefore, the Combo test had a sensitivity of 0% (95% CI 0%-28%) and positive predictive value of 0% for the detection of acute infections. The ability of Determine 4th Generation Combo to detect antigen was very poor in Swaziland. Thus, Determine Combo does not add any value to the current testing algorithm; rather it adds additional costs and complexity to HIV diagnosis. The detection of acute HIV infections may need to rely on other testing strategies. |
Development of a novel rapid HIV test for simultaneous detection of recent or long-term HIV type 1 infection using a single testing device
Granade TC , Nguyen S , Kuehl DS , Parekh BS . AIDS Res Hum Retroviruses 2013 29 (1) 61-7 Laboratory assays for the detection of recent HIV infection for HIV incidence surveillance are essential to HIV prevention efforts worldwide because they can identify populations with a high incidence and allow targeting of resources and monitoring of incidence trends over time. This study describes the development of a novel rapid HIV-1 incidence-prevalence (I-P) test that can be used for the simultaneous detection and discrimination of prevalent (long-term) or incident (recent) HIV infections using a single device. A lateral flow assay was developed that uses a multisubtype recombinant gp41 protein applied at two concentrations of antigen (high and low). Prevalent and incident HIV-1 infections can be distinguished based on differential antibody binding at the two antigen concentrations. High level/high avidity antibodies present in prevalent infections bind to and are detected at both antigen concentrations while low level/low avidity antibodies present in recent HIV infections are detected only at the higher antigen concentration line. A total of 205 HIV-positive specimens with known status (recent=105, long-term=100), including 57 specimens from seroconversion panels, were tested by the rapid I-P assay and the results were compared to the HIV-1 BED capture enzyme immunoassay (CEIA). There was a 95.1% agreement of final classification (recent or long-term) with the BED assay (kappa=0.910) (mean recency period=162 days) and a high correlation between the intensity score of the low antigen line with the BED OD-n (Pearson correlation=0.89). The new rapid I-P test has great potential to simplify HIV surveillance efforts by simultaneously providing information on both HIV prevalence and incidence using a single, rapid test device. |
Detection of recent HIV-1 infection using a new Limiting-Antigen Avidity Assay: potential for HIV-1 incidence estimates and avidity maturation studies
Duong YT , Qiu M , De AK , Jackson K , Dobbs T , Kim AA , Nkengasong JN , Parekh BS . PLoS One 2012 7 (3) e33328 BACKGROUND: Accurate and reliable laboratory methods are needed for estimation of HIV-1 incidence to identify the high-risk populations and target and monitor prevention efforts. We previously described a single-well limiting-antigen avidity enzyme immunoassay (LAg-Avidity EIA) to detect recent HIV-1 infection. METHODS: We describe here further optimization and characterization of LAg-Avidity EIA, comparing it to the BED assay and a two-well avidity-index (AI) EIA. Specimen sets included longitudinal sera (n = 393), collected from 89 seroconverting individuals from 4 cohorts representing 4 HIV-1 subtypes, and sera from AIDS patients (n = 488) with or without TB co-infections from 3 different cohorts. Ninety seven HIV-1 positive specimens were purchased commercially. The BED assay, LAg-Avidity EIA, AI-EIA and HIV serology were performed, as needed. RESULTS: Monitoring quality control specimens indicated high reproducibility of the LAg-Avidity EIA with coefficient of variation of <10% in the dynamic range. The LAg-Avidity EIA has an overall mean duration of recency (omega) of 141 days (95% CI 119-160) at normalized optical density (ODn) cutoff of 1.0, with similar omega in different HIV-1 subtypes and populations (132 to 143 days). Antibody avidity kinetics were similar among individuals and subtypes by both the LAg-Avidity EIA and AI-EIA compared to the HIV-IgG levels measured by the BED assay. The false recent rate among individuals with AIDS was 0.2% with the LAg-Avidity EIA, compared to 2.9% with the BED assay. Western blot profiles of specimens with increasing avidity confirm accurate detection of recent HIV-1 infections. CONCLUSIONS: These data demonstrate that the LAg-Avidity EIA is a promising assay with consistent omega in different populations and subtypes. The assay should be very useful for 1) estimating HIV-1 incidence in cross-sectional specimens as part of HIV surveillance, 2) identifying risk factors for recent infections, 3) measuring impact of prevention programs, and 4) studying avidity maturation during vaccine trials. |
HIV testing in developing countries: what is required?
Alemnji G , Nkengasong JN , Parekh BS . Indian J Med Res 2011 134 (6) 779-86 HIV diagnostic and follow up testing are usually done in laboratory settings. However, in developing countries there is a need to decentralize testing as the majority of the population lives in rural settings. In developing countries stringent quality assurance (QA) practices, which include appropriate training, development of standard operating procedures, maintenance of operator proficiency, routine use of quality control (QC) specimens, standardized data management, equipment calibration and maintenance, and biohazard safety with proper disinfection/disposal procedures are not routinely followed to ensure reliability of results and a safe work environment. The introduction of point-of-care testing technologies involving the use of non-laboratorians in routine testing has further increased the complexity of QA. Therefore, a careful approach towards improvement of laboratories that encourages best practices, coupled with incentives, and review of government policies in point-of-care testing is needed to improve quality of testing as decentralization takes place. Development of a functional laboratory tiered network that facilitates communication, referral, training and problem solving could further enhance confidence in laboratory testing. There is also a need for special considerations in implementing a step-wise approach towards quality improvement, strengthening of the supply chain management, human capacity development, infrastructure upgrade, and strong public private partnerships to ensure long term sustainability of these efforts. |
A comprehensive evaluation of the proficiency testing program for the HIV-1 BED incidence assay
Dobbs T , Liu X , Anderson R , Nkengasong J , Parekh BS . J Clin Microbiol 2011 49 (10) 3470-3 The HIV-1 BED incidence assay was developed at the Centers for Disease Control and Prevention (CDC) and since 2005 is available as a commercial kit for use in HIV-1 incidence surveillance. A BED-specific proficiency testing (PT) program was initiated in 2006 which included a panel of 8 coded specimens (6 unique and 2 duplicates) to participating laboratories. Number of participating laboratories increased from 12 to 38 from 2006 to 2009; Overall, 96.1% of laboratories reported results and 95.4% of those reporting achieved 100% score. Observed mean normalized optical density (OD-n) values of all participants correlated well with expected OD-n values for all specimens (R(2)=0.98) used for 7 PT rounds. BED testing demonstrated high reproducibility among all laboratories with agreement of 99.3% (574/578) between initial and confirmatory classification and regression statistics of R(2)=0.96, slope=1.022 and intercept=0.0066. Reproducibility among duplicate specimens was very high during each PT round with mean deviation of 1.8%. Analysis of controls and calibrator specimen for all 343 runs showed a coefficient of variation (CV) of about 20% for raw OD in the dynamic range, which was reduced to <=10% when OD was normalized (OD-n). Most laboratories that failed the PT assessment had transcriptional errors, kit reagent problems or specimen handling errors. Thus, the BED-specific PT program enabled us to track performance of different laboratories conducting the BED assay while identifying areas for improvements. This program will also serve as a template for future PT programs for new incidence assays as they become available. |
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