Last data update: Jun 03, 2024. (Total: 46935 publications since 2009)
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Query Trace: Ellenberger D [original query] |
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Progress in scale up of HIV viral load testing in select sub-Saharan African countries 2016-2018
Fonjungo PN , Lecher S , Zeh C , Rottinghaus E , Chun H , Adje-Toure C , Lloyd S , Mwangi JW , Mwasekaga M , Eshete YM , Pati R , Mots'oane T , Mitruka K , Beukes A , Mwangi C , Bowen N , Hamunime N , Beard RS , Kabuje A , Nabadda S , Auld AF , Balachandra S , Zungu I , Kandulu J , Alemnji G , Ehui E , Alexander H , Ellenberger D . PLoS One 2023 18 (3) e0282652 INTRODUCTION: We assessed progress in HIV viral load (VL) scale up across seven sub-Saharan African (SSA) countries and discussed challenges and strategies for improving VL coverage among patients on anti-retroviral therapy (ART). METHODS: A retrospective review of VL testing was conducted in Côte d'Ivoire, Kenya, Lesotho, Malawi, Namibia, Tanzania, and Uganda from January 2016 through June 2018. Data were collected and included the cumulative number of ART patients, number of patients with ≥ 1 VL test result (within the preceding 12 months), the percent of VL test results indicating viral suppression, and the mean turnaround time for VL testing. RESULTS: Between 2016 and 2018, the proportion of PLHIV on ART in all 7 countries increased (range 5.7%-50.2%). During the same time period, the cumulative number of patients with one or more VL test increased from 22,996 to 917,980. Overall, viral suppression rates exceeded 85% for all countries except for Côte d'Ivoire at 78% by June 2018. Reported turnaround times for VL testing results improved in 5 out of 7 countries by between 5.4 days and 27.5 days. CONCLUSIONS: These data demonstrate that remarkable progress has been made in the scale-up of HIV VL testing in the seven SSA countries. |
HIV viral load scale-up among children and adolescents: Trends in viral load suppression, sample type and processing in 7 PEPFAR countries, 2015-2018
Hrapcak S , Pals S , Itoh M , Peters N , Carpenter D , Hackett S , Prao AK , Adje-Toure C , Eboi E , Mutisya I , Nyabiage Omoto L , Ondondo RO , Bowen N , Nyanya W , Kayira D , Kaba MD , Mwenda R , Deus MI , Almeida J , Cuco RMM , Boylan A , Beard S , Ashikoto S , van Rooyen G , Kindra G , Diallo K , Carmona S , Nazziwa E , Mwangi C , Ntale J , Ssewanyana I , Nabadda SN , Nabukenya M , Ellenberger D , Rivadeneira E . Pediatr Infect Dis J 2023 42 (4) e102-e104 HIV-positive children and adolescents face gaps in viral load (VL) testing. To understand trends in pediatric/adolescent VL testing, 7 countries collected data from Laboratory Information Management Systems. Results showed increasing proportion of VL tests done through dried blood spot (DBS) and decreased sample rejection rates for DBS compared with plasma, supporting use of DBS VL when skilled phlebotomy is unavailable. |
Viral load scale-up in south Sudan: Strategic implementation of tools to monitor HIV treatment success among people living with HIV
Chun H , Russell A , Abe G , Katoro J , Songok J , Lesuk G , Worku H , Ukaejiofo O , Lodiongo D , Olemukun R , Kenigsberg T , Aragaw S , Deng LL , Bunga S , Ellenberger D . Int J STD AIDS 2022 33 (8) 9564624221103045 INTRODUCTION: As access to antiretroviral therapy (ART) for people with HIV (PWH) in the Republic of South Sudan (RSS) increases, viral load (VL) suppression is critical to protect global HIV response investments. We describe VL scale-up between 2017-2020 in the RSS President's Emergency Plan for AIDS Relief (PEPFAR)-supported program. METHODS: President's Emergency Plan for AIDS Relief (PEPFAR) South Sudan developed a VL scale-up plan and tools spanning the VL cascade: pre-test, test and post-test and included assessment of clinical facility and laboratory readiness; clinical and laboratory forms and standard operating procedures for test ordering, specimen collection, processing, results return and utilization; procedures to map clients, monitor turn-around-times (TAT), and an electronic system to monitor VL performance. RESULTS: Between 2017 to 2020, VL monitoring was established in 58 facilities, with 59,600 VL samples processed, and improvements in TAT (150-28 days) and rejection rates (1.9%-0.8%). VL documentation improved for dates of ART initiation, VL test request and dispatch, and HIV regimen. Total average time from high VL to repeat VL decreased from 15.9 months to 6.4 months in 2017 and 2019, respectively. CONCLUSIONS: A concerted approach to VL scale-up has been fundamental as South Sudan strives towards UNAIDS 95-95-95 targets for PWH on ART. |
HIV Viral Load Monitoring Among Patients Receiving Antiretroviral Therapy - Eight Sub-Saharan Africa Countries, 2013-2018
Lecher SL , Fonjungo P , Ellenberger D , Toure CA , Alemnji G , Bowen N , Basiye F , Beukes A , Carmona S , de Klerk M , Diallo K , Dziuban E , Kiyaga C , Mbah H , Mengistu J , Mots'oane T , Mwangi C , Mwangi JW , Mwasekaga M , N'Tale J , Naluguza M , Ssewanyana I , Stevens W , Zungu I , Bhairavabhotla R , Chun H , Gaffga N , Jadczak S , Lloyd S , Nguyen S , Pati R , Sleeman K , Zeh C , Zhang G , Alexander H . MMWR Morb Mortal Wkly Rep 2021 70 (21) 775-778 One component of the Joint United Nations Programme on HIV/AIDS (UNAIDS) goal to end the HIV/AIDS epidemic by 2030, is that 95% of all persons receiving antiretroviral therapy (ART) achieve viral suppression.(†) Thus, testing all HIV-positive persons for viral load (number of copies of viral RNA per mL) is a global health priority (1). CDC and other U.S. government agencies, as part of the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), together with other stakeholders, have provided technical assistance and supported the cost for multiple countries in sub-Saharan Africa to expand viral load testing as the preferred monitoring strategy for clinical response to ART. The individual and population-level benefits of ART are well understood (2). Persons receiving ART who achieve and sustain an undetectable viral load do not transmit HIV to their sex partners, thereby disrupting onward transmission (2,3). Viral load testing is a cost-effective and sustainable programmatic approach for monitoring treatment success, allowing reduced frequency of health care visits for patients who are virally suppressed (4). Viral load monitoring enables early and accurate detection of treatment failure before immunologic decline. This report describes progress on the scale-up of viral load testing in eight sub-Saharan African countries from 2013 to 2018 and examines the trajectory of improvement with viral load testing scale-up that has paralleled government commitments, sustained technical assistance, and financial resources from international donors. Viral load testing in low- and middle-income countries enables monitoring of viral load suppression at the individual and population level, which is necessary to achieve global epidemic control. Although there has been substantial achievement in improving viral load coverage for all patients receiving ART, continued engagement is needed to reach global targets. |
Expansion of viral load testing and the potential impact on human immunodeficiency virus drug resistance
Chun HM , Obeng-Aduasare YF , Broyles LN , Ellenberger D . J Infect Dis 2017 216 S808-S811 Increasing the volume, strengthening the quality, and proactively using data of human immunodeficiency virus (HIV) load testing are pivotal to limiting the threat of HIV drug resistance (HIVDR) accumulation,and allow for optimal case-based HIVDR surveillance. Triangulation of viral load (VL) and HIVDR testing data could be pursued to answer key questions and translate data and results for program and public policy. Identification of virologic failure and early management mitigates the greater risk of HIVDR. Routine VL monitoring and evaluation systems are necessary, and countries should consider reviewing system requirements, structural needs, and procedural and technical factors for the entire VL cascade, with special emphasis on post-test result use. |
Evaluation of the performance of Abbott m2000 and Roche COBAS Ampliprep/COBAS Taqman assays for HIV-1 viral load determination using dried blood spots and dried plasma spots in Kenya
Zeh C , Ndiege K , Inzaule S , Achieng R , Williamson J , Chih-Wei Chang J , Ellenberger D , Nkengasong J . PLoS One 2017 12 (6) e0179316 BACKGROUND: Routine HIV viral load testing is not widely accessible in most resource-limited settings, including Kenya. To increase access to viral load testing, alternative sample types like dried blood spots (DBS), which overcome the logistic barriers associated with plasma separation and cold chain shipment need to be considered and evaluated. The current study evaluated matched dried blood spots (DBS) and dried plasma spots (DPS) against plasma using the Abbott M 2000 (Abbott) and Roche Cobas Ampliprep/Cobas TaqMan (CAP/CTM) quantitative viral load assays in western Kenya. METHODS: Matched plasma DBS and DPS were obtained from 200 HIV-1 infected antiretroviral treatment (ART)-experienced patients attending patient support centers in Western Kenya. Standard quantitative assay performance parameters with accompanying 95% confidence intervals (CI) were assessed at the assays lower detection limit (400cps/ml for CAP/CTM and 550cps/ml for Abbott) using SAS version 9.2. Receiver operating curves (ROC) were further used to assess viral-load thresholds with best assay performance (reference assay CAP/CTM plasma). RESULTS: Using the Abbott test, the sensitivity and specificity, respectively, for DPS were (97.3%, [95%CI: 93.2-99.2] and 98.1% [95%CI: 89.7-100]) and those for DBS (93.9% [95%CI: 88.8-97.2] and 88.0% [95%CI: 82.2-92.4]). The correlation and agreement using paired plasma and DPS/DBS were strong, with r2 = 90.5 and rc = 68.1. The Bland-Altman relative percent change was 95.3 for DPS, (95%CI: 90.4-97.7) and 73.6 (95%CI: 51.6-86.5) for DBS. Using the CAP/CTM assay, the sensitivity for DBS was significantly higher compared to DPS (100.0% [95% CI: 97.6-100.0] vs. 94.7% [95%CI: 89.8-97.7]), while the specificity for DBS was lower: 4%, [95% CI: 0.4-13.7] compared to DPS: 94.0%, [95% CI: 83.5-98.7]. When compared under different clinical relevant thresholds, the accuracy for the Abbott assay was 95% at the 1000cps/ml cut-off with a sensitivity and specificity of 96.6% [95% CI 91.8-98.7] and 90.4% [95% CI 78.2-96.4] respectively. The optimum threshold was at 3000 cps/ml with an accuracy of 95.5%, sensitivity and specificity of 94.6% [95%CI 89.3-97.5] and 98.1% [95%CI 88.4-99.9]) respectively. The best threshold for CAP/CTM was at 4000 copies /mL, with 92.5% accuracy (sensitivity of 96.0% [95%CI 91.0-98.3] and specificity of 82.7% [95%CI 69.2-91.3]). CONCLUSIONS: There was similar performance between matched DBS, DPS and plasma using the Abbott test, and good correlation for matched DPS and plasma using the CAPCTM test. The findings suggest that DBS and DPS may be reliably used as alternative specimens to plasma to measure HIV-1 VL using Abbott, and DPS may be reliably used with CAP/CTM in resource-limited settings. |
Progress with scale-up of HIV viral load monitoring - seven sub-Saharan African countries, January 2015-June 2016
Lecher S , Williams J , Fonjungo PN , Kim AA , Ellenberger D , Zhang G , Toure CA , Agolory S , Appiah-Pippim G , Beard S , Borget MY , Carmona S , Chipungu G , Diallo K , Downer M , Edgil D , Haberman H , Hurlston M , Jadzak S , Kiyaga C , MacLeod W , Makumb B , Muttai H , Mwangi C , Mwangi JW , Mwasekaga M , Naluguza M , Ng'Ang ALw , Nguyen S , Sawadogo S , Sleeman K , Stevens W , Kuritsky J , Hader S , Nkengasong J . MMWR Morb Mortal Wkly Rep 2016 65 (47) 1332-1335 The World Health Organization (WHO) recommends viral load testing as the preferred method for monitoring the clinical response of patients with human immunodeficiency virus (HIV) infection to antiretroviral therapy (ART). Viral load monitoring of patients on ART helps ensure early diagnosis and confirmation of ART failure and enables clinicians to take an appropriate course of action for patient management. When viral suppression is achieved and maintained, HIV transmission is substantially decreased, as is HIV-associated morbidity and mortality. CDC and other U.S. government agencies and international partners are supporting multiple countries in sub-Saharan Africa to provide viral load testing of persons with HIV who are on ART. This report examines current capacity for viral load testing based on equipment provided by manufacturers and progress with viral load monitoring of patients on ART in seven sub-Saharan countries (Cote d'Ivoire, Kenya, Malawi, Namibia, South Africa, Tanzania, and Uganda) during January 2015-June 2016. By June 2016, based on the target numbers for viral load testing set by each country, adequate equipment capacity existed in all but one country. During 2015, two countries tested >85% of patients on ART (Namibia [91%] and South Africa [87%]); four countries tested <25% of patients on ART. In 2015, viral suppression was >80% among those patients who received a viral load test in all countries except Cote d'Ivoire. Sustained country commitment and a coordinated global effort is needed to reach the goal for viral load monitoring of all persons with HIV on ART. |
Analysis of roof and pillar failure associated with weak floor at a limestone mine
Murphy MM , Ellenberger JL , Esterhuizen GS , Miller T . Int J Min Sci Technol 2016 26 (3) 471-476 A limestone mine in Ohio has had instability problems that have led to massive roof falls extending to the surface. This study focuses on the role that weak, moisture-sensitive floor has in the instability issues. Previous NIOSH research related to this subject did not include analysis for weak floor or weak bands and recommended that when such issues arise they should be investigated further using a more advanced analysis. Therefore, to further investigate the observed instability occurring on a large scale at the Ohio mine, FLAC3D numerical models were employed to demonstrate the effect that a weak floor has on roof and pillar stability. This case study will provide important information to limestone mine operators regarding the impact of weak floor causing the potential for roof collapse, pillar failure, and subsequent subsidence of the ground surface. |
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. |
Early diagnosis of HIV infection in infants - one Caribbean and six sub-Saharan African countries, 2011-2015
Diallo K , Kim AA , Lecher S , Ellenberger D , Beard RS , Dale H , Hurlston M , Rivadeneira M , Fonjungo PN , Broyles LN , Zhang G , Sleeman K , Nguyen S , Jadczak S , Abiola N , Ewetola R , Muwonga J , Fwamba F , Mwangi C , Naluguza M , Kiyaga C , Ssewanyana I , Varough D , Wysler D , Lowrance D , Louis FJ , Desinor O , Buteau J , Kesner F , Rouzier V , Segaren N , Lewis T , Sarr A , Chipungu G , Gupta S , Singer D , Mwenda R , Kapoteza H , Chipeta Z , Knight N , Carmona S , MacLeod W , Sherman G , Pillay Y , Ndongmo CB , Mugisa B , Mwila A , McAuley J , Chipimo PJ , Kaonga W , Nsofwa D , Nsama D , Mwamba FZ , Moyo C , Phiri C , Borget MY , Ya-Kouadio L , Kouame A , Adje-Toure CA , Nkengasong J . MMWR Morb Mortal Wkly Rep 2016 65 (46) 1285-1290 Pediatric human immunodeficiency virus (HIV) infection remains an important public health issue in resource-limited settings. In 2015, 1.4 million children aged <15 years were estimated to be living with HIV (including 170,000 infants born in 2015), with the vast majority living in sub-Saharan Africa. In 2014, 150,000 children died from HIV-related causes worldwide. Access to timely HIV diagnosis and treatment for HIV-infected infants reduces HIV-associated mortality, which is approximately 50% by age 2 years without treatment. Since 2011, the annual number of HIV-infected children has declined by 50%. Despite this gain, in 2014, only 42% of HIV-exposed infants received a diagnostic test for HIV, and in 2015, only 51% of children living with HIV received antiretroviral therapy (1). Access to services for early infant diagnosis of HIV (which includes access to testing for HIV-exposed infants and clinical diagnosis of HIV-infected infants) is critical for reducing HIV-associated mortality in children aged <15 years. Using data collected from seven countries supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), progress in the provision of HIV testing services for early infant diagnosis was assessed. During 2011-2015, the total number of HIV diagnostic tests performed among HIV-exposed infants within 6 weeks after birth (tests for early infant diagnosis of HIV), as recommended by the World Health Organization (WHO) increased in all seven countries (Cote d'Ivoire, the Democratic Republic of the Congo, Haiti, Malawi, South Africa, Uganda, and Zambia); however, in 2015, the rate of testing for early infant diagnosis among HIV-exposed infants was <50% in five countries. HIV positivity among those tested declined in all seven countries, with three countries (Cote d'Ivoire, the Democratic Republic of the Congo, and Uganda) reporting >50% decline. The most common challenges for access to testing for early infant diagnosis included difficulties in specimen transport, long turnaround time between specimen collection and receipt of results, and limitations in supply chain management. Further reductions in HIV mortality in children can be achieved through continued expansion and improvement of services for early infant diagnosis in PEPFAR-supported countries, including initiatives targeted to reach HIV-exposed infants, ensure access to programs for early infant diagnosis of HIV, and facilitate prompt linkage to treatment for children diagnosed with HIV infection. |
Early antiretroviral therapy initiation: Access and equity of viral load testing for HIV treatment monitoring
Peter T , Ellenberger D , Kim AA , Boeras D , Messele T , Roberts T , Stevens W , Jani I , Abimiku A , Ford N , Katz Z , Nkengasong JN . Lancet Infect Dis 2016 17 (1) e26-e29 Scaling up access to HIV viral load testing for individuals undergoing antiretroviral therapy in low-resource settings is a global health priority, as emphasised by research showing the benefits of suppressed viral load for the individual and the whole population. Historically, large-scale diagnostic test implementation has been slow and incomplete because of service delivery and other challenges. Building on lessons from the past, in this Personal View we propose a new framework to accelerate viral load scale-up and ensure equitable access to this essential test. The framework includes the following steps: (1) ensuring adequate financial investment in scaling up this test; (2) achieving pricing agreements and consolidating procurement to lower prices of the test; (3) strengthening functional tiered laboratory networks and systems to expand access to reliable, high-quality testing across countries; (4) strengthening national leadership, with prioritisation of laboratory services; and (5) demand creation and uptake of test results by clinicians, nurses, and patients, which will be vital in ensuring viral load tests are appropriately used to improve the quality of care. The use of dried blood spots to stabilise and ship samples from clinics to laboratories, and the use of point-of-care diagnostic tests, will also be important for ensuring access, especially in settings with reduced laboratory capacity. For countries that have just started to scale up viral load testing, lessons can be learnt from countries such as Botswana, Brazil, South Africa, and Thailand, which have already established viral load programmes. This framework might be useful for guiding the implementation of viral load with the aim of achieving the new global HIV 90-90-90 goals by 2020. |
Determination of volumetric changes at an underground stone mine: A photogrammetry case study
Slaker B , Westman E , Ellenberger J , Murphy M . Int J Min Sci Technol 2015 26 (1) 149-154 Photogrammetry, as a tool for monitoring underground mine deformation, is an alternative to traditional point measurement devices, and may be capable of accurate measurements in situations where technologies such as laser scanning are unsuited, undesired, or cost-prohibitive. An underground limestone mine in Ohio is used as a test case for monitoring of structurally unstable pillars. Seven pillars were photographed over in a 63day period, punctuated by four visits. Using photogrammetry, point clouds of the mine geometry were obtained and triangulation surfaces were generated to determine volumes of change over time. Pillar spalling in the range of 0.29-4.03m3 of rock on individual rib faces was detected. Isolated incidents of rock expansion prior to failure, and the isolated failure of a weak shale band were also observed. Much of the pillars remained unchanged during the monitoring period, which is indicative of proper alignment in the triangulated surfaces. The photographs of some ribs were of either too poor quality or had insufficient overlap, and were not included. However, photogrammetry was successfully applied to multiple ribs in quantifying the pillar geometry change over time. |
Performance of an early infant diagnostic test, AmpliSens DNA-HIV-FRT, using dried blood spots collected from children bBorn to human immunodeficiency virus-infected mothers in Ukraine
Chang J , Tarasova T , Shanmugam V , Azarskova M , Nguyen S , Hurlston M , Sabatier J , Zhang G , Osmanov S , Ellenberger D , Yang C , Vitek C , Liulchuk M , Nizova N . J Clin Microbiol 2015 53 (12) 3853-8 An accurate accessible test for early infant diagnosis (EID) is crucial for identifying HIV-infected infants and linking them to treatment. To improve EID services in Ukraine, dried blood spot (DBS) samples obtained from 237 HIV-exposed children (≤18 months of age) in six regions in Ukraine in 2012 to 2013 were tested with the AmpliSens DNA-HIV-FRT assay, the Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HIV-1 Qual test, and the Abbott RealTime HIV-1 Qualitative assay. In comparison with the paired whole-blood results generated from AmpliSens testing at the oblast HIV reference laboratories in Ukraine, the sensitivity was 0.99 (95% confidence interval [CI], 0.95 to 1.00) for the AmpliSens and Roche CAP/CTM Qual assays and 0.96 (95% CI, 0.90 to 0.98) for the Abbott Qualitative assay. The specificity was 1.00 (95% CI, 0.97 to 1.00) for the AmpliSens and Abbott Qualitative assays and 0.99 (95% CI, 0.96 to 1.00) for the Roche CAP/CTM Qual assay. McNemar analysis indicated that the proportions of positive results for the tests were not significantly different (P > 0.05). Cohen's kappa (0.97 to 0.99) indicated almost perfect agreement among the three tests. These results indicated that the AmpliSens DBS and whole-blood tests performed equally well and were comparable to the two commercially available EID tests. More importantly, the performance characteristics of the AmpliSens DBS test meets the World Health Organization EID test requirements; implementing AmpliSens DBS testing might improve EID services in resource-limited settings. |
Scale-up of HIV viral load monitoring - seven Sub-Saharan African countries
Lecher S , Ellenberger D , Kim AA , Fonjungo PN , Agolory S , Borget MY , Broyles L , Carmona S , Chipungu G , De Cock KM , Deyde V , Downer M , Gupta S , Kaplan JE , Kiyaga C , Knight N , MacLeod W , Makumbi B , Muttai H , Mwangi C , Mwangi JW , Mwasekaga M , Ng'Ang ALw , Pillay Y , Sarr A , Sawadogo S , Singer D , Stevens W , Toure CA , Nkengasong J . MMWR Morb Mortal Wkly Rep 2015 64 (46) 1287-90 To achieve global targets for universal treatment set forth by the Joint United Nations Programme on human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (UNAIDS), viral load monitoring for HIV-infected persons receiving antiretroviral therapy (ART) must become the standard of care in low- and middle-income countries (LMIC) (1). CDC and other U.S. government agencies, as part of the President's Emergency Plan for AIDS Relief, are supporting multiple countries in sub-Saharan Africa to change from the use of CD4 cell counts for monitoring of clinical response to ART to the use of viral load monitoring, which is the standard of care in developed countries. Viral load monitoring is the preferred method for immunologic monitoring because it enables earlier and more accurate detection of treatment failure before immunologic decline. This report highlights the initial successes and challenges of viral load monitoring in seven countries that have chosen to scale up viral load testing as a national monitoring strategy for patients on ART in response to World Health Organization (WHO) recommendations. Countries initiating viral load scale-up in 2014 observed increases in coverage after scale-up, and countries initiating in 2015 are anticipating similar trends. However, in six of the seven countries, viral load testing coverage in 2015 remained below target levels. Inefficient specimen transport, need for training, delays in procurement and distribution, and limited financial resources to support scale-up hindered progress. Country commitment and effective partnerships are essential to address the financial, operational, technical, and policy challenges of the rising demand for viral load monitoring. |
Monitoring the quality of HIV-1 viral load testing through proficiency testing program using dried tube specimens in resource-limited settings
Nguyen S , Ramos A , Chang J , Li B , Shanmugam V , Boeras D , Nkengasong JN , Yang C , Ellenberger D . J Clin Microbiol 2015 53 (4) 1129-36 BACKGROUND: HIV-1 RNA viral load (VL) levels are used for monitoring disease progression and antiretroviral therapy outcomes in HIV-infected patients. To assess the performance of laboratories conducting HIV-1 VL testing in resource-limited settings, the US Centers for Disease Control and Prevention implemented a voluntary, free-of-charge, external quality assurance program using dried tube specimens (DTSs). METHODS: DTS proficiency test (PT) panels consisting of 5 specimens were distributed between 2010 and 2012 at ambient temperature to participants. The results from participants (N ≥ 6) using the same assay were grouped, analyzed, and graded as acceptable within a group mean +/- 3SDs. Mean proficiency scores were calculated by dividing the combined PT scores with the number of testing cycles using a linear regression model. RESULTS: Between 2010 and 2012, the number of participants enrolled increased from 32 in 16 countries to 114 in 44 countries. 78.2% of participants reported results using 10 different VL assays. The rates of participants reporting acceptable results were 96.6% (Abbott), 96.3% (Roche COBAS), 94.5% (Roche Amplicor), 93.0% (Biocentric), and 89.3% (NucliSENS). The overall mean proficiency scores improved over time (p = 0.024). CONCLUSION: DTSs are a good alternative specimen type to plasma specimens for VL PT programs as they do not require cold chain transportation and can be used on polymerase chain reaction (PCR)-based assays. Our data suggest that the CDC HIV-1 VL PT program using DTSs positively impacts the testing performance of the participants which might translate into better and accurate VL testing services to patients. |
Limited utility of dried-blood- and plasma spot-based screening for antiretroviral treatment failure with Cobas Ampliprep/TaqMan HIV-1 version 2.0.
Sawadogo S , Shiningavamwe A , Chang J , Maher AD , Zhang G , Yang C , Gaeb E , Kaura H , Ellenberger D , Lowrance DW . J Clin Microbiol 2014 52 (11) 3878-83 The 2013 WHO antiretroviral therapy (ART) guidelines recommend dried blood spots (DBS) as an alternative specimen type for viral load (VL) monitoring. We assessed the programmatic utility of screening for ARV treatment failure (TF) at 5,000 and 1,000 copies/mL using DBS and dried plasma spots (DPS) with a commonly used VL assay, the Roche COBAS Ampliprep/COBAS TaqManV.2.0 (CAP/CTM). Plasma, DBS, and DPS were prepared from 839 whole-blood specimens collected from patients on ART ≥ six months at three public facilities in Namibia. VL was measured in plasma, DBS and DPS using the CAP/CTM and results were compared using plasma VL as the reference standard. The clinical sensitivity, specificity, Positive and Negative Predictive Value, (PPV and NPV) of DBS were 0.99, 0.55, 0.33 and 0.99, and 0.99, 0.26, 0.29 and 0.99 at ARV TF diagnostic thresholds of 5,000 copies/mL and 1,000 copies/mL, respectively; for DPS, they were 0.88, 0.98, 0.92 and 0.97, and 0.91, 0.96, 0.89, and 0.97 at TF diagnostic thresholds of 5,000 copies/mL and 1,000 copies/mL, respectively. TF prevalence in DBS was overestimated by 33% and 57% at the two thresholds, respectively. A high rate of false-positive results would occur if the CAP/CTM with DBS were used to screen for ARV TF. WHO recommendations for DBS-based VL monitoring should be specific to VL assay version and type. Despite the higher performance of DPS, the programmatic utility for TF screening may be limited by requirements for processing the whole blood at the collection site. |
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. |
Roof instability: what reportable noninjury roof falls in underground coal mines can tell us
Bajpayee TS , Pappas DM , Ellenberger JL . Prof Saf 2014 59 (3) 57-62 Roof falls are a major hazard in underground mining. Roof bolting is the primary means of supporting the mine roof in underground coal mines. Despite great strides in the design of support systems, roof falls continue to occur in bolted areas. Noninjury roof fall reports provide insight into the characteristics of roof falls. This study examined 11,600 noninjury roof fall reports to identify geological contributors to roof falls. The goal is to provide data that can help improve roof-fall-related safety by providing direction for the research and development of improved support systems and mine layout alternatives. |
Field evaluation of Abbott Real Time HIV-1 Qualitative Test for early infant diagnosis using dried blood spots samples in comparison to Roche COBAS Ampliprep/COBAS TaqMan HIV-1 Qual Test in Kenya
Chang J , Omuomo K , Anyango E , Kingwara L , Basiye F , Morwabe A , Shanmugam V , Nguyen S , Sabatier J , Zeh C , Ellenberger D . J Virol Methods 2014 204 25-30 Timely diagnosis and treatment of infants infected with HIV are critical for reducing infant mortality. High-throughput automated diagnostic tests like Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Qual Test (Roche CAPCTM Qual) and the Abbott Real Time HIV-1 Qualitative (Abbott Qualitative) can be used to rapidly expand early infant diagnosis testing services. In this study, the performance characteristics of the Abbott Qualitative were evaluated using two hundred dried blood spots (DBSs) samples (100 HIV-1 positive and 100 HIV-1 negative) collected from infants attending the antenatal facilities in Kisumu, Kenya. The Abbott Qualitative results were compared to the diagnostic testing completed using the Roche CAPCTM Qual in Kenya. The sensitivity and specificity of the Abbott Qualitative were 99.0% (95% CI: 95.0-100.0) and 100.0% (95% CI: 96.0-100.0), respectively, and the overall reproducibility was 98.0% (95% CI: 86.0-100.0). The limits of detection for the Abbott Qualitative and Roche CAPCTM Qual were 56.5 and 6.9copies/mL at 95% CIs (p=0.005), respectively. The study findings demonstrate that the Abbott Qualitative test is a practical option for timely diagnosis of HIV in infants. |
Impact of proficiency testing program for laboratories conducting early infant diagnosis of HIV-1 in low to middle-income countries
Garcia A , Subbarao S , Zhang G , Parsons L , Nkengasong J , Ou CY , Ellenberger D . J Clin Microbiol 2013 52 (3) 773-80 A voluntary, cost-free external quality assessment (EQA) program established by the U.S. Centers for Disease Control and Prevention (CDC) was implemented to primarily monitor the performance of laboratories conducting HIV Early Infant Diagnosis (EID) from dried blood spots (DBS) in low to middle-income countries since 2006. Ten blinded DBS proficiency test (PT) specimens and 100 known HIV-positive and negative DBS specimens (to be used as internal controls) were shipped tri-annually to participating laboratories with reports for the PT specimens due within 30 days. The participant's results and summary of the performance of all participating laboratories and each diagnostic method were provided after each test cycle. Enrollment in the CDC PT program expanded progressively from 17 laboratories from 11 countries in 2006 to include 136 laboratories from 41 countries at the end of 2012. Despite external pressures to test and treat more children while expanding EID programs, mean PT test scores significantly improved over time as demonstrated by the upward trend from mid-2006 to end of 2012 (P = 0.001) and increase in the percentage of laboratories scoring 100% (P =0.003). The mean test scores plateaued over the past 10 testing cycles, ranging between 98.2 and 99.7% and discordant test results still occur, but at a rate no higher than 2.6%. Analysis of these test results suggests a positive impact of proficiency testing on the testing performance of the participating laboratories and a continuous training program and proficiency testing participation may translate into laboratories improving their testing accuracy. |
Susceptibility to repeated, low-dose, rectal SHIVSF162P3 challenge is independent of TRIM5 genotype in rhesus macaques.
Butler K , Morgan JS , Hanson DL , Adams DR , Garcia-Lerma G , Heneine PW , Ellenberger D , Hendry RM , McNicholl JM , Johnson W , Kersh EN . AIDS Res Hum Retroviruses 2013 29 (7) 1091-4 Infections following repeated, low-dose (RLD), mucosal S(H)IV exposures of macaques are used to model sexual HIV exposures for biomedical prevention testing. Different susceptibilities among animals can complicate study designs. In rhesus macaques, TRIM5 alleles Q, CypA, and TFP, are resistance factors for infection with some S(H)IV strains, but not for SIVmac239 due to its capsid properties. SIVmac239-derived SHIVSF162P3 has been demonstrated to reproducibly infect mucosally in vaginal and rectal RLD models. To further test the suitability of SHIVSF162P3 for RLD models, we studied the influence of TRIM5 genotype on susceptibility to rectal RLD infection and on plasma viremia by analyzing 43 male Indian rhesus macaques from control arms of completed studies. The median number of exposures required for infection was: 3 (Q/Q, n=4) (TRIM5 alleles, number of macaques, respectively); 4 (Q/CypA, n=7), 3 (TFP/Q, n=15); 3 (TFP/TFP, n=15); 2 (TFP/CypA, n=2); TRIM5CypA/CypA was not represented in our study. Median peak viremia (log10 viral copies/mL) in infected animals was: 7.4 (Q/Q, n=4); 7.2 (Q/CypA, n=6), 7.3 (TFP/Q, n=13); 7.1 (TFP/TFP, n=15); 6.5 (TFP/CypA; n=2). Neither susceptibility nor peak viremia were significantly different (log-rank test, Kruskal Wallis test, respectively). Rhesus macaques' susceptibility to RLD SHIVSF162P3 is independent of TRIM5 TFP, CypA, and Q alleles, with the limitation that the power to detect any impact of CypA/CypA and TFP/CypA genotypes was nonexistent or low, due to absence or infrequency, respectively. The finding that TRIM5 alleles do not restrict mucosal infection or ensuing replication rates suggests that SHIVSF162P3 is indeed suitable for RLD experimentation. |
Generation of dried tube specimen for HIV-1 viral load proficiency test panels: a cost-effective alternative for external quality assessment programs
Ramos A , Nguyen S , Garcia A , Subbarao S , Nkengasong JN , Ellenberger D . J Virol Methods 2012 188 1-5 Participation in external quality assessment programs is critical to ensure quality clinical laboratory testing. Commercially available proficiency test panels for HIV-1 virus load testing that are used commonly in external quality assessment programs remain a financial obstacle to resource-limited countries. Maintaining cold-chain transportation largely contributes to the cost of traditional liquid proficiency test panels. Therefore, we developed and evaluated a proficiency test panel using dried tube specimens that can be shipped and stored at ambient temperature. This dried tube specimens panel consisted of 20mcl aliquots of a HIV-1 stock that were added to 2ml tubes and left uncapped for drying, as a preservation method. The stability of dried tube specimens at concentrations ranging from 10(2) to 10(6.5) RNA copies/ml was tested at different temperatures over time, showing no viral load reduction at 37 degrees C and a decrease in viral load smaller than 0.5 Log(10) at 45 degrees C for up to eight weeks when compared to initial results. Eight cycles of freezing-thawing had no effect on the stability of the dried tube specimens. Comparable viral load results were observed when dried tube specimen panels were tested on Roche CAPTAQ, Abbott m2000, and Biomerieux easyMAG viral load systems. Preliminary test results of dried proficiency test panels shipped to four African countries at ambient temperature demonstrated a low inter assay variation (SD range: 0.29-0.41 Log(10) RNA copies/ml). These results indicated that HIV-1 proficiency test panels generated by this methodology might be an acceptable alternative for laboratories in resource-limited countries to participate in external quality assessment programs. |
Evaluation of blood collection filter papers for HIV-1 DNA PCR.
Masciotra S , Khamadi S , Bile E , Puren A , Fonjungo P , Nguyen S , Girma M , Downing R , Ramos A , Subbarao S , Ellenberger D . J Clin Virol 2012 55 (2) 101-6 BACKGROUND: The collection of dried blood spots (DBS) on Whatman 903 cards has facilitated for years the detection of HIV-1 in infants by DNA PCR as early as 4-6 weeks after birth in resource-limited settings (RLS), but alternate blood collection devices are proving to be necessary. OBJECTIVES: The qualitative detection of HIV-1 DNA by PCR from DBS prepared on three commercially available blood collection cards was evaluated at the Centers for Disease Control and Prevention (CDC) and in four laboratories in Africa. STUDY DESIGN: DBS were prepared on Ahlstrom grade 226, Munktell TFN and Whatman 903, and stored under a variety of conditions. DBS were stored at ambient temperature (RT), 37 degrees C with high humidity, and -20 degrees C for varying lengths of time. The presence of HIV-1 DNA was tested using Roche Amplicor HIV-1 DNA (v 1.5) weekly for 4 weeks and at weeks 8 and 12 (RT and 37 degrees C), at weeks 4, 8, and 18 (-20 degrees C) of storage. DBS specimens were also tested after international shipment at RT. In addition, after nearly 3 years storage at -20 degrees C, DBS were also evaluated independently using the COBAS Ampliprep/TaqMan HIV-1 Qual and Abbott RealTime HIV-1 Qualitative tests. RESULTS: HIV-1 DNA was detected equally well on the three blood collection cards regardless of storage conditions and PCR assay. CONCLUSIONS: Ahlstrom 226 and Munktell TFN papers were comparable to Whatman 903 for HIV-1 DNA detection and may be considered as optional blood collection devices in resource-limited countries. |
Opportunities and challenges for cost-efficient implementation of new point-of-care diagnostics for HIV and tuberculosis
Schito M , Peter TF , Cavanaugh S , Piatek AS , Young GJ , Alexander H , Coggin W , Domingo GJ , Ellenberger D , Ermantraut E , Jani IV , Katamba A , Palamountain KM , Essajee S , Dowdy DW . J Infect Dis 2012 205 Suppl 2 S169-80 Stakeholders agree that supporting high-quality diagnostics is essential if we are to continue to make strides in the fight against human immunodeficiency virus (HIV) and tuberculosis. Despite the need to strengthen existing laboratory infrastructure, which includes expanding and developing new laboratories, there are clear diagnostic needs where conventional laboratory support is insufficient. Regarding HIV, rapid point-of-care (POC) testing for initial HIV diagnosis has been successful, but several needs remain. For tuberculosis, several new diagnostic tests have recently been endorsed by the World Health Organization, but a POC test remains elusive. Human immunodeficiency virus and tuberculosis are coendemic in many high prevalence locations, making parallel diagnosis of these conditions an important consideration. Despite its clear advantages, POC testing has important limitations, and laboratory-based testing will continue to be an important component of future diagnostic networks. Ideally, a strategic deployment plan should be used to define where and how POC technologies can be most efficiently and cost effectively integrated into diagnostic algorithms and existing test networks prior to widespread scale-up. In this fashion, the global community can best harness the tremendous capacity of novel diagnostics in fighting these 2 scourges. |
Evaluation of a high-throughput diagnostic system for detection of HIV-1 in dried blood spot samples from infants in Mozambique.
Jani IV , Sabatier J , Vubil A , Subbarao S , Bila D , de Sousa A , Mabunda N , Garcia A , Skaggs B , Ellenberger D , Ramos A . J Clin Microbiol 2012 50 (4) 1458-60 We performed a comparative analysis between Roche Amplicor HIV-1 DNA test and CAPTAQ assay for the detection of HIV in 830 dried blood spot (DBS) pediatric samples collected in Mozambique. Our results demonstrated no statistical difference between these assays. The CAPTAQ assay approached nearly 100% repeatability/accuracy. The increased throughput of testing with minimal operator interference in performing the CAPTAQ assay clearly demonstrated that this method is an improvement over the Roche Amplicor HIV-1 DNA test, version 1.5. |
Early diagnosis of HIV infection in the breastfed infant
Ou CY , Fiscus S , Ellenberger D , Parekh B , Korhonen C , Nkengasong J , Bulterys M . Adv Exp Med Biol 2012 743 51-65 More than 90% of the 370,000 pediatric human immunodeficiency virus type 1 (HIV-1) infections globally in 2009 were acquired through mother-to-child transmission (MTCT) [1], and most of these transmissions occurred in sub-Saharan Africa. MTCT of HIV-1 occurs either during late pregnancy, the intrapartum period, or breastfeeding [2, 3]. With the application of prophylactic antiretroviral (ARV) therapy and breastfeeding avoidance, MTCT is now observed in only 1–2% of at-risk infants in developed countries [4, 5]. The majority of pregnant women residing in high HIV-burden, resource-limited countries (RLCs) are still not aware of their infection status and do not receive timely intervention measures to prevent vertical transmission [6–11]. Untreated infected infants have high HIV-related morbidity and mortality. Approximately 33% of the untreated infected infants in RLCs die during their first year of life, and >50% die within their first 2 years [12]. Treating infants early greatly reduces mortality and morbidity [13]. Recognition of the importance of reducing infant HIV mortality has facilitated the development of methods to bring appropriate testing closer to pregnant and lactating mothers, to identify HIV-infected infants earlier, and to provide timely access to life-saving ARV treatment and care. New and accurate diagnostic methods have emerged in the last few years, and many of these methods have been field-validated. This diagnostic service should not comprise a stand-alone program but must be integrated into the overall mother and child health programs to achieve the goal of prevention of mother-to-child transmission (PMTCT) [14, 15]. In this chapter, we review currently available diagnostic methodologies, including their advantages and disadvantages, their testing algorithms, and their quality assurance requirements, with a particular focus on early HIV diagnosis in the breastfed infant. Further, we discuss efforts toward the development of simple, accurate, and rapid diagnostic applications. |
Pillar strength in underground stone mines in the United States
Esterhuizen GS , Dolinar DR , Ellenberger JL . Int J Rock Mech Min Sci 2011 48 (1) 42-50 Stone mines in the Eastern and Midwestern United States make use of the room-and-pillar method of mining to extract relatively flat-laying sedimentary formations. A survey of pillar performance was carried out to identify potential modes of instability. Pillars were found to have been successful in providing support to the overburden, but a small number of individual failed pillars were observed. Failure of the pillars was observed to be related to spalling of the hard brittle rocks, shearing along pre-existing angular discontinuities or progressive extrusion of soft infill materials on bedding planes. A method of estimating the pillar strength and selecting a safety factor for design was developed based on observations of stable and failed pillars, supplemented by numerical models. The developed pillar strength equation can be used to design stable stone mine pillars provided the rock conditions are similar to those included in the study. Published by Elsevier Ltd. |
Generation of a dual RT Env SHIV that is infectious in rhesus macaques
Smith JM , Dauner A , Li B , Srinivasan P , Mitchell J , Hendry M , Ellenberger D , Butera S , Otten RA . J Med Primatol 2010 39 (4) 213-23 BACKGROUND: The best current animal model for HIV infection and evaluation of antiviral compounds is the Simian-human immunodeficiency virus (SHIV)/macaque system. There are multiple recombinant SHIVs available, but these viruses have limitations in evaluating combination drug strategies for prevention. Drug combinations that target reverse transcriptase (RT, either nRTI or nnRTI) and envelope (entry or fusion inhibitors) have to be tested separately, which does not permit the assessment of additive, synergistic, or antagonistic effects of ARV combinations. We describe construction of a dual SHIV containing both HIV RT and a CCR5-specific HIV envelope gene in a simian immunodeficiency virus backbone. METHODS: The RT Env SHIV molecular clone was constructed using RT SHIV and SHIV162p3 sequences as templates to generate RT Env SHIV. RT Env SHIV was expanded in vitro in CD8-depleted macaque peripheral blood mononuclear cells (PBMC). Recombinant virus was used to infect a rhesus macaque (4.3 x 10(4) tissue culture infectious dose [TCID(50)], intravenously [IV]). A second passage in a macaque by IV transfer of 10 ml of blood obtained from the first infection was also done. The in vivo adapted virus stock from these macaques was used to produce high titer stocks in vitro and used to rectally infect an additional macaque. RESULTS: Peak viral load reached 6 x 10(5) vRNA copies/ml in plasma in both IV-exposed macaques and remained detectable in the one animal for 16 weeks after infection. A viral stock (1.68 x 10(4) TCID(50)) derived from the second macaque passage has been produced in CD8-depleted rhesus PBMC and was successfully used to demonstrate mucosal transmission. The resulting RT Env SHIV retained the sensitivity to HIV RT and entry inhibitors of its parental viruses. CONCLUSIONS: The objective of this study was to develop and characterize a SHIV recombinant virus for evaluating the efficacy of ART and microbicide products that target both HIV RT and/or Env-mediated entry. RT Env SHIV can productively infect macaques by both the IV and mucosal route, making it a valuable tool for transmission studies. |
Repeated rectal SHIVSF162P3 exposures do not consistently induce sustained T cell responses prior to systemic Infection in the repeat-low dose preclinical macaque model
Kersh EN , Luo W , Adams DR , Srinivasan P , Smith JM , Promadej-Lanier N , Ellenberger D , Garcia-Lerma JG , Butera S , Otten R . AIDS Res Hum Retroviruses 2009 25 (9) 905-17 The macaque model of repeated SHIV exposures is increasingly used as a preclinical tool to evaluate biomedical HIV intervention strategies. It is unclear whether multiple virus exposures induce immune responses in macaques, as documented in uninfected individuals repeatedly exposed to HIV. We here address whether repeated, rectal SHIV(SF162P3) exposures lead to systemic T cell activation in 12 rhesus macaques, and whether this is associated with increased infection resistance. Eight macaques became systemically infected after 2-7 exposures, three macaques were less susceptible (infection after 10-12 exposures), and one macaque remained uninfected after 14 exposures. PBMCs were retrospectively monitored for increases in T cell activation by analyzing the proportion of CD8(+) T cells, recently activated or proliferated T cells (markers CD38, Ki67), a marker for cytotoxicity (granzyme B), or T cell-produced plasma cytokines (IFN-gamma, RANTES, IL-2). Repeated virus exposures did not induce sustained, potent, or diverse T cell responses prior to systemic infection. Some changes occurred in the analyzed parameters during repeated virus exposures, but similar T cell activities were also observed in five SHIV-unexposed control macaques. Thus, we found no evidence that delayed infection or resistance to infection was associated with systemic, long-lasting, protective T cell responses to repeated rectal virus exposures. Our results provide further insights into the repeat exposure macaque model. We find that this model can be used for testing biomedical prevention strategies without concern of eliciting a systemic vaccination effect. |
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