SUNScholar - Browsing by Author "Preiser, Wolfgang"

Browsing by Author "Preiser, Wolfgang"

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38 years after its discovery, Ebola virus spins out of control
(South African Centre for Epidemiological Modelling and Analysis (SACEMA), 2014-09) Preiser, Wolfgang
The evolutionary origin of Ebolaviruses is not very clear. The simple notion that these viruses have been circulating for many millennia in wildlife in tropical parts of Africa, occasionally spilling over into human populations, often brought on by human activities, may not be correct or at least incomplete. Over time a number of Ebola disease outbreaks reported and a pattern in the outbreak response seemed to have been established. A lot was also learnt about Ebola viruses, their epidemiology and ecology. However, the 2014 Ebola outbreak challenges our understanding in many respects.
Academic publishing in pandemic times
(ASSAf, 2020-09-21) Preiser, Wolfgang; Preiser, Rika
ENGLISH ABSTRACT: Even though it tends to feel like ages, it has not been that long since the final days of 2019, when cases of severe respiratory illness (now known as COVID-19), caused by a previously unknown coronavirus (since named SARSCoV- 2), were reported from China. The ongoing COVID-19 pandemic has brought unprecedented disruption to almost every area of our daily and professional lives. Science has not been spared, nor has scientific publishing. Most researchers have been unable to continue with their work, and many had to all but re-invent their teaching. Quite a few have re-invented themselves as coronavirus researchers.1 As biomedical researchers, we are astonished to see how much interest the public is taking in our findings. For no other disease do members of the public so fervently seek out reports in traditional and social media about the latest research findings. These reports often trigger controversial discussions, mostly on social media platforms, about rather complicated aspects of epidemiology, diagnostics, pathogenesis or therapy. Many of these issues are matters outside the realm of everyday life and normally left to experts to assess the evidence and translate it into practice.
Antibody responses to vaccination among South African HIV-exposed and unexposed uninfected infants during the first 2 years of life
(American Society for Microbiology, 2013-01) Reikie, Brian A.; Naidoo, Shalena; Ruck, Candice E.; Slogrove, Amy L.; De Beer, Corena; La Grange, Heleen; Adams, Rozanne C. M.; Ho, Kevin; Smolen, Kinga; Speert, David P.; Cotton, Mark F.; Preiser, Wolfgang; Esser, Monika; Kollmann, Tobias R.
HIV-exposed but uninfected (HEU) infants born to HIV-infected mothers from areas in the world with a high burden of infectious disease suffer higher infectious morbidity and mortality than their HIV unexposed uninfected (HUU) peers. Vaccination provides protection from infection. The possibility exists that altered response to vaccination contributes to the higher rate of infection in HEU than in HUU infants. While short-term, cross-sectional studies support this notion, it is unclear whether or not HEU infants develop long-term protective immune responses following theWHOextended program on immunization (EPI). Vaccine-specific antibody responses were compared between HEU and HUU infants from 2 weeks until 2 years of age in a longitudinal South African cohort. Total IgG and antibodies specific for Bordetella pertussis, Haemophilus influenzae type b (Hib), tetanus toxoid, hepatitis B virus (HepB), and measles virus were measured at multiple time points throughout the first 2 years of life. Prevaccine antibodies (maternal antibodies passively acquired) specific for tetanus were lower in HEU than in HUU infants, while prevaccine antibodies to HepB were higher in HEU than in HUU infants. Both groups responded similarly to tetanus, Hib, and HepB vaccination. HEU demonstrated stronger pertussis vaccine responses, developing protective titers 1 year earlier than HUU patients, and maintained higher anti-tetanus titers at 24 months of age. Vaccine-induced antibodies to measles virus were similar in both groups at all time points. Our results suggest that the current EPI vaccination program as practiced in South Africa leads to the development of vaccine-specific antibody responses that are equivalent in HEU and HUU infants. However, our data also suggest that a large fraction of both HEU and HUU South African infants have antibody titers for several infectious threats that remain below the level of protection for much of their first 2 years of life.
Close Relative of Human Middle East Respiratory Syndrome Coronavirus in Bat, South Africa
(Centers for Disease Control and Prevention (CDC), 2013-10) Ithete, Ndapewa Laudika; Stoffberg, Samantha; Corman, Victor Max; Cottontail, Veronika M.; Richards, Leigh Rosanne; Schoeman, M. Corrie; Drosten, Christian; Drexler, Jan Felix; Preiser, Wolfgang
We now report the identification of a South Africa bat derived CoV that has an even closer phylogenetic relationship with MERS-CoV.
Construction of a high titer infectious HIV-1 subtype C proviral clone from South Africa
(MDPI, 2012-09-24) Jacobs, Graeme Brendon; Bock, Stefanie; Schuch, Anita; Moschall, Rebecca; Schrom, Eva-Maria; Zahn, Juliane; Reuter, Christian; Preiser, Wolfgang; Rethwilm, Axel; Engelbrecht, Susan; Kerkau, Thomas; Bodem, Jochen
The Human Immunodeficiency Virus type 1 (HIV-1) subtype C is currently the predominant subtype worldwide. Cell culture studies of Sub-Saharan African subtype C proviral plasmids are hampered by the low replication capacity of the resulting viruses, although viral loads in subtype C infected patients are as high as those from patients with subtype B. Here, we describe the sequencing and construction of a new HIV-1 subtype C proviral clone (pZAC), replicating more than one order of magnitude better than the previous subtype C plasmids. We identify the env-region for being the determinant for the higher viral titers and the pZAC Env to be M-tropic. This higher replication capacity does not lead to a higher cytotoxicity compared to previously described subtype C viruses. In addition, the pZAC Vpu is also shown to be able to down-regulate CD4, but fails to fully counteract CD317.
COVID-19 : getting ahead of the epidemic curve by early implementation of social distancing
(Health & Medical Publishing Group, 2020) Preiser, Wolfgang; Van Zyl, Gert; Dramowski, Angela
The response to the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has largely been reactive. There are a few exceptions of countries taking proactive measures. Some countries in Asia, including Taiwan and Singapore, were able to limit the spread despite close links to China,[1,2] and South Korea and China were able to mobilise to contain an initial rapidly spreading epidemic through mass testing and early interventions.[2,3] As COVID-19 has now reached Africa, South Africa (SA) could be a regional leader in its response and reduce the impact of the disease on its population by acting early.
Delays in HIV-1 infant polymerase chain reaction testing may leave children without confirmed diagnoses in the Western Cape province, South Africa
(AOSIS, 2022-06) Mahlakwane, Kamela L.; Preiser, Wolfgang; Nkosi, Nokwazi; Naidoo, Nasheen; Van Zyl, Gert
Background: Early diagnosis and confirmation of HIV infection in newborns is crucial for expedited initiation of antiretroviral therapy. Confirmatory testing must be done for all children with a reactive HIV PCR result. There is no comprehensive data on confirmatory testing and HIV PCR test request rejections at National Health Laboratory Service laboratories in South Africa. Objective: This study assessed the metrics of routine infant HIV PCR testing at the Tygerberg Hospital Virology Laboratory, Cape Town, Western Cape, South Africa, including the proportion of rejected test requests, turn-around time (TAT), and rate of confirmatory testing. Methods: We retrospectively reviewed laboratory-based data on all HIV PCR tests performed on children ≤ 24 months old (n = 43 346) and data on rejected HIV PCR requests (n = 1479) at the Tygerberg virology laboratory over two years (2017–2019). Data from sample collection to release of results were analysed to assess the TAT and follow-up patterns. Results: The proportion of rejected HIV PCR requests was 3.3%; 83.9% of these were rejected for various pre-analytical reasons. Most of the test results (89.2%) met the required 96-h TAT. Of the reactive initial test results, 53.5% had a follow-up sample tested, of which 93.1% were positive. Of the initial indeterminate results, 74.7% were negative on follow-up testing. Conclusion: A high proportion of HIV PCR requests were rejected for pre-analytical reasons. The high number of initial reactive tests without evidence of follow-up suggests that a shorter TAT is required to allow confirmatory testing before children are discharged.
Diagnostic virology : excessive expenditure or essential contribution to health care?
(Stellenbosch : University of Stellenbosch, 2009) Preiser, Wolfgang; Editor: SU Language Centre
Inaugural address delivered by Prof Wolfgang Preiser on 15 September 2009.
Effects of prednisolone on disease progression in antiretroviral-untreated HIV infection : a 2-year randomized, double-blind placebo-controlled clinical trial
(Public Library of Science, 2016) Kasang, Christa; Kalluvya, Samuel; Majinge, Charles; Kongola, Gilbert; Mlewa, Mathias; Massawe, Irene; Kabyemera, Rogatus; Magambo, Kinanga; Ulmer, Albrecht; Klinker, Hartwig; Gschmack, Eva; Horn, Anne; Koutsilieri, Eleni; Preiser, Wolfgang; Hofmann, Daniela; Hain, Johannes; Müller, Andreas; Dölken, Lars; Weissbrich, Benedikt; Rethwilm, Axel; Stich, August; Scheller, Carsten
Background: HIV-disease progression correlates with immune activation. Here we investigated whether corticosteroid treatment can attenuate HIV disease progression in antiretroviral-untreated patients. Methods: Double-blind, placebo-controlled randomized clinical trial including 326 HIV-patients in a resource-limited setting in Tanzania (clinicaltrials.gov NCT01299948). Inclusion criteria were a CD4 count above 300 cells/μl, the absence of AIDS-defining symptoms and an ART-naïve therapy status. Study participants received 5 mg prednisolone per day or placebo for 2 years. Primary endpoint was time to progression to an AIDS-defining condition or to a CD4-count below 200 cells/μl. Results: No significant change in progression towards the primary endpoint was observed in the intent-to-treat (ITT) analysis (19 cases with prednisolone versus 28 cases with placebo, p = 0.1407). In a per-protocol (PP)-analysis, 13 versus 24 study participants progressed to the primary study endpoint (p = 0.0741). Secondary endpoints: Prednisolone-treatment decreased immune activation (sCD14, suPAR, CD38/HLA-DR/CD8+) and increased CD4-counts (+77.42 ± 5.70 cells/μl compared to -37.42 ± 10.77 cells/μl under placebo, p < 0.0001). Treatment with prednisolone was associated with a 3.2-fold increase in HIV viral load (p < 0.0001). In a post-hoc analysis stratifying for sex, females treated with prednisolone progressed significantly slower to the primary study endpoint than females treated with placebo (ITT-analysis: 11 versus 21 cases, p = 0.0567; PP-analysis: 5 versus 18 cases, p = 0.0051): No changes in disease progression were observed in men. Conclusions: This study could not detect any significant effects of prednisolone on disease progression in antiretroviral-untreated HIV infection within the intent-to-treat population. However, significant effects were observed on CD4 counts, immune activation and HIV viral load. This study contributes to a better understanding of the role of immune activation in the pathogenesis of HIV infection.
The epidemiology of hepatitis B virus infection in HIV-infected and HIV-uninfected pregnant women in the Western Cape, South Africa
(Elsevier, 2013-11) Andersson, M. I.; Maponga, T. G.; Ijaz, S.; Barnes, J.; Theron, G. B.; Meredith, S. A.; Preiser, Wolfgang; Tedder, R. S.
OBJECTIVES: Persistent hepatitis B virus (HBV) infection is a major cause of morbidity and mortality in sub-Saharan Africa. The HIV epidemic has the potential to affect its biology. Immunisation protocols established in the pre-HIV era are based upon data showing predominantly horizontal infant transmission. This study aimed to determine whether HIV co-infection will change the epidemiology of HBV both by increasing infectivity and by favouring the escape of viruses bearing phenotypically altered HBsAg. METHODS: This retrospective cross-sectional study used antenatal samples from the 2008 Antenatal Sentinel HIV and Syphilis Prevalence Survey in the Western Cape, South Africa. All HIV-infected women were age and race-matched to HIV-uninfected women. Samples were tested for serological markers of HBV and HDV infection. HBV viral load, consensus sequencing and genotyping were performed. Luminex technology was used to determine HBsAg phenotype. All samples from HIV-infected women were tested for traces of antiretroviral drugs by mass spectrometry. RESULTS: This study showed a trend toward loss of immune control of HBV in HIV-infected women with 3.4% of samples containing HBsAg, 18.9% contained HBeAg. In contrast, 2.9% of samples from HIV-uninfected women contained HBsAg and 17.1% of these HBeAg. The median HBV load in the HIV-infected group was 9.72×10(7)IU/ml and in the HIV-uninfected group 1.19×10(6)IU/ml. Genotyping showed 63/68 samples belonged to genotype A and the remainder genotype D. Mutations in the precore region were found in 35% and 33% of samples from HIV-infected and HIV-uninfected respectively. Although no major epitope ablation was found, marked variation in HBsAg profiles in HIV-infected group was demonstrated. No HDV infection was detected. CONCLUSION: HIV-HBV co-infected women exhibit a degree of immune escape. One in six HBV-infected pregnant women, irrespective of HIV status is HBeAg seropositive. HBV immunization of newborns in sub-Saharan Africa should be implemented.
From easing lockdowns to scaling up community-based coronavirus disease 2019 screening, testing, and contact tracing in Africa-shared approaches, innovations, and challenges to minimize morbidity and mortality
(Oxford University Press, 2020-05) Nachega, Jean B.; Grimwood, Ashraf; Mahomed, Hassan; Fatti, Geoffrey; Preiser, Wolfgang; Kallay, Oscar; Mbala, Placide K.; Muyembe, Jean-Jacques T.; Rwagasore, Edson; Nsanzimana, Sabin; Ngamije, Daniel; Condo, Jeanine; Sidat, Mohsin; Noormahomed, Emilia V.; Reid, Michael; Lukeni, Beatrice; Suleman, Fatima; Mteta, Alfred; Zumla, Alimuddin
The arrival of coronavirus disease 2019 (COVID-19) on the African continent resulted in a range of lockdown measures that curtailed the spread of the infection but caused economic hardship. African countries now face difficult choices regarding easing of lockdowns and sustaining effective public health control measures and surveillance. Pandemic control will require efficient community screening, testing, and contact tracing; behavioral change interventions; adequate resources; and well-supported, community-based teams of trained, protected personnel. We discuss COVID-19 control approaches in selected African countries and the need for shared, affordable, innovative methods to overcome challenges and minimize mortality. This crisis presents a unique opportunity to align COVID-19 services with those already in place for human immunodeficiency virus, tuberculosis, malaria, and non communicable diseases through mobilization of Africa's interprofessional healthcare workforce. By addressing the challenges, the detrimental effect of the COVID-19 pandemic on African citizens can be minimized.
From easing lockdowns to scaling-up community-based COVID-19 screening, testing, and contact tracing in Africa : shared approaches, innovations, and challenges to minimize morbidity and mortality
(Oxford University Press, 2020) Nachega, Jean B.; Grimwood, Ashraf; Mahomed, Hassan; Fatti, Geoffrey; Preiser, Wolfgang; Kallay, Oscar; Mbala, Placide K.; Muyembe, Jean-Jacques T.; Rwagasore, Edson; Nsanzimana, Sabin; Ngamije, Daniel; Condo, Jeanine; Sidat, Moshin; Noormahomed, Emilia V.; Reid, Michael; Lukeni, Beatrice; Suleman, Fatima; Mteta, Alfred; Zumla, Alimuddin
The arrival of COVID-19 to the African continent resulted in a range of locally relevant lockdown measures, which curtailed the spread of SARS-CoV-2 but caused economic hardship for large sections of the population. African countries now face difficult choices regarding easing of lockdowns and sustaining effective public health control measures and surveillance. Control of the COVID-19 pandemic will require efficient community screening, testing, contact tracing, and behavioral change interventions, adequate resources, and a well-supported, community-based team of trained, protected personnel. We discuss COVID-19 screening-testing-contact tracing approaches used in selected African countries and the need for shared, affordable, innovative methods to overcome challenges and minimize mortality rates. This crisis presents a unique opportunity to align COVID-19 services with those already in place for HIV, TB, Malaria, and other non-communicable diseases (NCDs) through mobilization of Africa's inter-professional healthcare workforce to contain the pandemic. By addressing the challenges, the detrimental effect of the COVID-19 pandemic on African citizens can be minimized.
HBV and HIV viral load but not microbial translocation or immune activation are associated with liver fibrosis among patients in South Africa
(BioMed Central, 2018-05-08) Maponga, Tongai Gibson; Andersson, Monique I.; Van Rensburg, Christoffel J.; Arends, Joop E.; Taljaard, Jantjie; Preiser, Wolfgang; Glashoff, Richard H.
Background: Co-infection with HIV negatively impacts the progression of chronic hepatitis B virus (HBV) infection, including causing rapid progression to liver fibrosis. Sub-Saharan Africa represents arguably the most important intersection of high endemicity of both chronic hepatitis B virus (HBV) infection and HIV infection. Methods: We recruited 46 HBV/HIV-co-infected; 47 HBV-monoinfected; 39 HIV-monoinfected; and 37 HBV/HIV-uninfected patients from Tygerberg Hospital, Cape Town, South Africa. All HIV-infected patients were on antiretroviral therapy for ≥3 months. Liver stiffness measurements were assessed using the Fibroscan (Fibroscan 402, Echosens). Cell-based immunomarkers were measured by flow cytometry. Soluble serum/plasma immunomarkers were measured by Luminex technology and enzyme immunoassays. HIV (COBAS/Ampliprep TaqMan HIV-1) and HBV viral loads (in-house assay) were also performed. Results: HBV/HIV co-infected patients showed significantly higher levels of immune activation %CD8+/HLA-DR+/CD38+ (median 30%, interquartile range: 17–53) and %CD8+/PD-1 (median 22%, interquartile range: 15–33), p ≤ 0.01 compared to all other study groups. Despite this, the HBV-mono-infected group had the highest proportion of patients with advanced liver fibrosis (≥13 kPa) as measured by Fibroscan (18%). HBV mono-infected patients showed highest expression of most cytokines including IL-17 and basic fibroblastic growth factor. There was significant positive correlation between detectable HIV and HBV viral replication and liver fibrosis but not immune activation or gut translocation. Discussion: Highly-active antiretroviral therapy, including tenofovir, is effective against both HIV and HBV. Earlier therapy in the co-infected patients may therefore have controlled viral replication leading to better fibrosis scores when compared to HBV mono-infection in this study. On-going HBV and HIV viraemia, rather than microbial translocation or immune activation, appear to be the drivers of liver fibrosis. Moderate to advanced liver fibrosis in HBV-mono-infection may well indicate poor access to screening and treatment of HBV infection.
Hepatitis B virus drug resistance mutations in HIV/HBV co-infected children in Windhoek, Namibia
(Public Library of Science, 2020-09-11) Tchuem, Cynthia Raissa Tamandjou; Brandt, Laura; Nel, Etienne De la Rey; Cotton, Mark Fredric; Matthews, Philippa; Kaindjee-Tjituka, Francina; Preiser, Wolfgang; Andersson, Monique Ingrid
ENGLISH ABSTRACT: In patients who are HIV infected, hepatitis B virus (HBV) infection is an important co-morbidity. However, antiretroviral options for HIV/HBV co-infected children are limited and, at the time of this study, only included lamivudine. These children may remain on this regimen for many years until late adolescence. They are at high risk of developing HBV drug resistance and uncontrolled HBV disease. The aim of this study was to characterize HBV infection in HIV/HBV co-infected children. Known HIV-infected/HBsAg-positive children, previously exposed to lamivudine monotherapy against HBV, and their mothers were recruited at the Katutura Hospital paediatric HIV clinic in Windhoek, Namibia. Dried blood spot and serum samples were collected for HBV characterization and serological testing, respectively. Fifteen children and six mothers participated in the study. Eight of the 15 children (53.3%) tested HBV DNA positive; all eight children were on lamivudine-based ART. Lamivudine-associated resistance variants, together with immune escape mutants in the surface gene, were identified in all eight children. Resistance mutations included rtL80I, rtV173L, rtL180M, rtM204I/V and the overlapping sE164D, sW182*, sI195M and sW196LS variants. HBV strains belonged to genotypes E (6/8, 75%) and D3 (2/8, 25%). Further analysis of the HBV core promoter region revealed mutations associated with reduced expression of HBeAg protein and hepatocarcinogenesis. All six mothers, on HBV-active ART containing tenofovir and lamivudine, tested HBV DNA negative. This study confirms the importance of screening HIV-infected children for HBV and ensuring equity of drug access to effective HBV treatment if co-infected.
Hepatitis B virus infection in HIV-exposed infants in the Western Cape, South Africa
(Elsevier, 2015-07) Chotun, Nafiisah; Nel, Etienne; Cotton, Mark F.; Preiser, Wolfgang; Andersson, Monique I.; Pathology: Medical Virology
Hepatitis B virus infection (HBV) is a significant public health problem in sub-Saharan Africa. Universal infant vaccination with the hepatitis B (HB) vaccine has been implemented within the South African Expanded Programme of Immunization since April 1995 with concomitant reduction in HBV infection in children. However, the first vaccine dose is only administered at six weeks of age. This delay may lead to a failure to reduce the risk of perinatal HBV transmission to infants born to HIV/HBV co-infected women, in whom HBV infection is often upregulated. The aim of this study was to determine the prevalence of HBV infection in babies born to HIV-infected mothers in the Western Cape, South Africa. HBV serological markers were tested in all infant serum samples and following HB viral load testing, sequencing and genotyping were also performed. Three of 1000 samples screened tested positive for HBsAg and HBV DNA. An additional infant tested positive for HBV DNA alone. All babies had received the HB vaccine at 6, 10 and 14 weeks. The prevalence of HBV infection was therefore 4/1000 (0.4%; 95% CI, 0.01–0.79%). Three of four infants and all four mothers were followed-up. Two infants were persistently positive for HBsAg with viral loads above 108 International Units per millilitre. All four maternal samples were positive for HBsAg and HBeAg and one was also positive for anti-HBe. Sequencing analysis of two mother–child HBV pairs showed 100% sequence identity. This study demonstrates HBV infection in HIV-exposed infants despite HB vaccination from 6 weeks of age. A more strategic approach is needed to prevent mother to child transmission of HBV, including screening of pregnant women, HBV-targeted antiviral therapy and HB birth dose vaccine.
Hepatitis B virus-associated hepatocellular carcinoma in South Africa in the era of HIV
(BMC (part of Springer Nature), 2020-07-13) Maponga, Tongai Gibson.; Glashoff, Richard H.; Vermeulen, Hannali; Robertson, Barbara; Burmeister, Sean; Bernon, Marc; Omoshoro-Jones, Jones; Ruff, Paul; Neugut, Alfred I.; Jacobson, Judith S.; Preiser, Wolfgang; Andersson, Monique I.
Background: Patients co-infected with hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are at risk of developing hepatocellular carcinoma (HCC). In sub-Saharan Africa, the overlap between high HIV and HBV prevalence may increase the incidence of HCC. This study investigated the impact of HBV/HIV co-infection on age at presentation and survival of HCC. Methods: Ethical approval was obtained to recruit, following informed written consent, patients diagnosed with HCC at oncology units at four South African hospitals. Between December 2012 and August 2015, patients newly diagnosed with HCC were recruited and provided demographic and clinical data and blood specimens. Patients were tested for HBV, hepatitis C virus (HCV) and HIV. Survival data was available for a subset of patients. Results: Of 107 HCC cases, 83 (78%) were male. Median age was 46 years (range 18 to 90 years), 68/106 (64%) were HBsAg-positive, and 22/100 (22%) were HIV infected. Among HBV surface antigen (HBsAg)-positive HCC cases, 18/66 (27%) were HIV-infected compared to 3/34 (9%) among those that were HBsAg-negative (p = 0.04). A greater proportion of HBV/HIV co-infected cases were female than HBV mono-infected (6/18, 33% vs 6/47, 13%; p = 0.005). In addition, HBV/HIV co-infected females presented at a younger mean age (36.8 years) than HBV mono-infected women (50.5 years) (p = 0.09). Median survival was 82 days among the HIV-infected HCC patients compared to 181 days among those without HIV (p = 0.15). Conclusions: HCC is an important complication in the HIV/HBV infected patient. HIV-positive patients presented with HCC at a younger age than HIV-negative patients, this effect appears to be greater in women. These data provide more evidence supporting the call to address. HCC as a cause of morbidity and mortality in the HBV/HIV co-infected patient population. (281 words).
High positive HIV serology results can still be false positive
(Elsevier, 2019) Reid, Joanna; Van Zyl, Gert; Linstrom, Michael; Korsman, Stephen; Marais, Gert; Preiser, Wolfgang
ENGLISH ABSTRACT: The consequences of falsely reactive HIV test results can be significant, for patients and healthcare providers. This case describes a diagnostic investigation of a patient with pronounced discordant HIV serological results, to determine HIV status. The fourth generation serological screening assay (Roche COBAS Elecsys HIV combiPT) had high positive results but confirmatory testing was negative (Abbott HIV Ag/Ab Combo). Five separate samples over 13 days were tested using multiple fourth generation HIV immunoassays and molecular tests for HIV-1 and HIV-2. Potential causes of falsely reactive serological results were investigated. Samples were sent to the manufacturer for analysis. The screening assay was positive on all samples with a very high signal to cut-off ratio (S/CO) of greater than 400. However, multiple serological and molecular assays did not detect HIV-1 or HIV-2 specific antibodies, antigen or nucleic acid. A recombinant immunochromatographic assay had faint reactivity to gp41 peptide and the manufacturer investigation reported cross-reactivity to one of the screening assay’s synthetic peptides. Possible causes of the false positive result include cross reactivity to other antigens, including prior schistosomiasis infection, or the patient’s previously excised ameloblastoma (a rare germ cell tumor of the jaw). This is a rare case of false high positive results on fourth-generation HIV serology testing due to high level non-specific reactivity to an isolated synthetic peptide component of the assay. It highlights the need for confirmatory testing even in settings with HIV high prevalence and awareness that false-positive serological results may have a high S/CO.
HIV Drug Resistance (HIVDR) in antiretroviral therapy-naive patients in Tanzania not eligible for WHO Threshold HIVDR survey is dramatically high
(Public Library of Science (PLoS), 2011-08-19) Kasang, Christa; Kalluvya, Samuel; Majinge, Charles; Stich, August; Bodem, Jochen; Kongola, Gilbert; Jacobs, Graeme Brendon; Mlewa, Mathias; Mildner, Miriam; Hensel, Irina; Horn, Anne; Preiser, Wolfgang; Van Zyl, Gert; Klinker, Hartwig; Koutsilieri, Eleni; Rethwilm, Axel; Scheller, Carsten; Weissbrich, Benedikt; Kallas, Esper Georges
BACKGROUND: The World Health Organization (WHO) has recommended guidelines for a HIV drug resistance (HIVDR) survey for resource-limited countries. Eligibility criteria for patients include age below 25 years in order to focus on the prevalence of transmitted HIVDR (tHIVDR) in newly-infected individuals. Most of the participating sites across Africa have so far reported tHIVDR prevalences of below 5%. In this study we investigated whether the rate of HIVDR in patients <25 years is representative for HIVDR in the rest of the therapy-naïve population. Methods and Findings HIVDR was determined in 88 sequentially enrolled ART-naïve patients from Mwanza, Tanzania (mean age 35.4 years). Twenty patients were aged <25 years and 68 patients were aged 25–63 years. The frequency of HIVDR in the study population was 14.8% (95%; CI 0.072–0.223) and independent of NVP-resistance induced by prevention of mother-to-child transmission programs. Patients >25 years had a significantly higher HIVDR frequency than younger patients (19.1%; 95% CI 0.095–0.28) versus 0%, P = 0.0344). In 2 out of the 16 patients with HIVDR we found traces of antiretrovirals (ARVs) in plasma. Conclusions ART-naïve patients aged over 25 years exhibited significantly higher HIVDR than younger patients. Detection of traces of ARVs in individuals with HIVDR suggests that besides transmission, undisclosed misuse of ARVs may constitute a significant factor in the generation of the observed high HIVDR rate. The current WHO tHIVDR survey that is solely focused on the transmission of HIVDR and that excludes patients over 25 years of age may therefore result in substantial underestimation of the prevalence of HIVDR in the therapy-naïve population. Similar studies should be performed also in other areas to test whether the so far reported optimistic picture of low HIVDR prevalence in young individuals is really representative for the rest of the ART-naïve HIV-infected population.
HIV-1 RNA testing of pooled dried blood spots is feasible to diagnose acute HIV infection in resource limited settings
(Medpharm Publications, 2018) Dowling, Wentzel; Veldsman, Kirsten; Katusiime, Mary Grace; Maritz, Jean; Bock, Peter; Meehan, Sue-Ann; Schalkwyk, Marije Van; Cotton, Mark F.; Preiser, Wolfgang; Van Zyl, Gert U.
Objectives: Rapid human immunodeficiency virus (HIV) antibody tests, routinely used for diagnosis in adults and older children in resource-limited settings (RLS), do not detect early HIV infections prior to seroconversion or when antibody levels are still low. Nucleic acid amplification to detect HIV-1 RNA is the most sensitive method for acute HIV infection diagnosis, but is costly. We therefore investigated HIV- 1 RNA testing of pooled dried blood spots (DBS) to diagnose acute HIV infection. Design: Laboratory-based investigation. Methods: DBS were collected from HIV-1 Voluntary Counselling and Testing (HVCT) clients who tested negative on the Advanced QualityTM HIV antibody rapid test. DBS samples from five participants were pooled and tested on the COBAS AmpliPrep/COBAS TaqMan HIV-1 (CAP/CTM) Test v2. Individual DBS were tested when pools tested positive (> 200 RNA copies/ml). Acute infection was confirmed by HIV viral load testing, two fourth-generation HIV serological assays, and Geenius™ HIV 1/2 Assay for antibody band identification. Results: Of 482 participants who were tested, one (0.2%) had acute HIV infection: Fourth generation serology was low-level positive, the plasma HIV viral load was 15 929 HIV-1 RNA copies/ml, gp160 and gp41 antibody bands were positive and the p31 band was negative, indicating a Fiebig Stage 5 infection. Conclusions: Pooled DBS HIV-1 RNA testing is efficient compared to individual testing for acute HIV infection diagnosis. Early identification of participants with acute HIV infection facilitates immediate initiation of antiretroviral therapy to improve immune recovery and prevent transmission to others.
HIV-1 viral load assays for resource-limited settings : clades matter
(Public Library of Science Medicine, 2006-12) Preiser, Wolfgang; Drexler, Jan Felix; Drosten, Christian

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