Increase in False Positive Fourth Generation HIV Tests in Patients with COVID-19 Disease.

BACKGROUND: We observed an increase in the frequency of false positive (FP) HIV test results correlating with SARS-CoV-2 prevalence, which led us to measure FP rates of a laboratory-based fourth generation HIV antigen/antibody test among those with polymerase-chain reaction (PCR)-confirmed infection with SARS-CoV-2 compared to the FP rate of those testing PCR-negative for SARS-CoV-2. METHODS: All those PCR tested for SARS-CoV-2 result within 2 weeks of a HIV fourth generation assay were selected. Positive HIV fourth generation assays were independently reviewed and divided into groups of FP, true positives (TP), and presumptive negatives (PN). Variables included age, race, ethnicity, gender, pregnancy, and COVID-19 immunization status. Associations with positive SARS-CoV-2 tests were assessed using linear logistic regression. A multivariate logistic regression was used to assess sets of variables. RESULTS: There were 31,910 medical records that met criteria. The frequency of SARS-CoV-2 positive tests was then calculated in groups of HIV TP, FP, and PN. In total, 31,575 patients had a PN HIV test result, 248 patients had a TP, and 87 patients had a FP. Those with HIV FP tests had the highest percentage of COVID-19 positive test results at 19.5%, which was significantly higher than HIV PN (11.3%; p = 0.016) and HIV TP (7.7%; p = 0.002). After adjustment for all covariates, only FP HIV was significantly associated with COVID-19 (odds ratio 4.22; p = 0.001). CONCLUSIONS: This study reveals those patients with positive SARS-CoV-2 PCR tests are significantly more likely to have a FP fourth generation HIV test than those with negative SARS-CoV-2 PCR tests.

Screening of potential donors for immunoglobulins M and G to new coronavirus infection

This study presents the results of the examination of potential donors of blood and its components for immunoglobulins M and G to patients with coronavirus disease 2019 (COVID-19) living in St. Petersburg. A total of 6782 people aged 18-24 years were evaluated, which accounted for 2.07% of the region's population (326 760 people) of this age group. The study was carried out in the spring and autumn of 2020. A negative result (absence of antibodies) was obtained in 93.5% of the participants. The rates of immunoglobulins M and M + G were 0.58% and 4.18%, respectively, in the spring and autumn. Moreover, the number of participants who had immunoglobulins M and G + M in the autumn period was four times higher than the indicators of the spring period, which indicated greater infection activities in the population during this period. This is most likely due to the active movement of the population in the summer. When comparing the rates of COVID-19 infection and the frequency of occurrence in donors of the same age, markers of human immunodeficiency virus 1 and 2 and hepatitis B and C in 2020 (0.024, 0.012 and 0.13%, respectively) indicate the urgency of the problem of donor selection during blood services, especially during a difficult epidemiological situation because of COVID-19. Along with organizational measures for the selection of donors (e.g., attracting individuals from organized groups in which there are no signs of an unfavorable epidemiological situation to donation), mandatory testing of potential donors for immunoglobulins M and G should be considered.

Resource and infrastructure challenges on the RESIST-2 Trial: an implementation study of drug resistance genotype-based algorithmic ART switches in HIV-2-infected adults in Senegal.

BACKGROUND: Second-line treatment of HIV-2 in resource-limited settings (RLS) is complicated by a lack of controlled trial data, limited availability of HIV-2-active antiretroviral drugs, and inadequate access to drug resistance testing. We conducted an implementation trial of a dried blood spot- (DBS) based, drug resistance genotype-informed antiretroviral therapy (ART) switching algorithm for HIV-2-infected patients in Senegal. METHODS: HIV-2-infected adults initiating or receiving ART through the Senegalese national AIDS program were invited to participate in this single-arm trial. DBS from participants with virologic failure (defined as viral load (VL) > 250 copies/mL after > 6 months on the current ART regimen) were shipped to Seattle for genotypic drug resistance testing. Participants with evidence of drug resistance in protease or reverse transcriptase were switched to new regimens according to a pre-specified algorithm. Participant clinical and immuno-virologic outcomes were assessed, as were implementation challenges. RESULTS: We enrolled 152 participants. Ten were initiating ART. The remainder were ART-experienced, with 91.0% virologically suppressed (< 50 copies/mL). Problems with viral load testing capability resulted in obtaining VL results for only 227 of 613 (37.0%) participant-visits. Six of 115 participants (5.2%) with VL available after > 6 months on current ART regimen experienced virologic failure, with per-protocol genotypic testing attempted. One additional test was performed for a participant with a VL of 222 copies/mL. Genotypes from three participants showed no evidence of major drug resistance mutations, two showed nucleoside reverse transcriptase inhibitor (NRTI) resistance, one showed both NRTI and protease inhibitor resistance, and one test failed. No integrase inhibitor resistance was observed. Five of six successfully-tested participants switched to the correct regimen or received additional adherence counseling according to the algorithm; the sixth was lost to follow-up. Follow-up VL testing was available for two participants; both of these were virally suppressed (< 10 copies/mL). The trial was terminated early due to the COVID-19 pandemic (which prevented further VL and genotypic testing), planned rollout of dolutegravir-based 1st-line ART, and funding. CONCLUSIONS: The RESIST-2 trial demonstrated that a DBS-based genotypic test can be used to help inform second-line ART decisions as part of a programmatic algorithm in RLS, albeit with significant implementation challenges. TRIAL REGISTRATION: ClinicalTrials.gov NCT03394196 . Registered on January 9, 2018.

Non-Canonical Translation Initiation Mechanisms Employed by Eukaryotic Viral mRNAs.

Viruses exploit the translation machinery of an infected cell to synthesize their proteins. Therefore, viral mRNAs have to compete for ribosomes and translation factors with cellular mRNAs. To succeed, eukaryotic viruses adopt multiple strategies. One is to circumvent the need for m7G-cap through alternative instruments for ribosome recruitment. These include internal ribosome entry sites (IRESs), which make translation independent of the free 5' end, or cap-independent translational enhancers (CITEs), which promote initiation at the uncapped 5' end, even if located in 3' untranslated regions (3' UTRs). Even if a virus uses the canonical cap-dependent ribosome recruitment, it can still perturb conventional ribosomal scanning and start codon selection. The pressure for genome compression often gives rise to internal and overlapping open reading frames. Their translation is initiated through specific mechanisms, such as leaky scanning, 43S sliding, shunting, or coupled termination-reinitiation. Deviations from the canonical initiation reduce the dependence of viral mRNAs on translation initiation factors, thereby providing resistance to antiviral mechanisms and cellular stress responses. Moreover, viruses can gain advantage in a competition for the translational machinery by inactivating individual translational factors and/or replacing them with viral counterparts. Certain viruses even create specialized intracellular "translation factories", which spatially isolate the sites of their protein synthesis from cellular antiviral systems, and increase availability of translational components. However, these virus-specific mechanisms may become the Achilles' heel of a viral life cycle. Thus, better understanding of the unconventional mechanisms of viral mRNA translation initiation provides valuable insight for developing new approaches to antiviral therapy.

Short Communication: Impact of COVID-19 on Case Reporting for HTLV and HIV-2 in Spain.

The medical demand imposed by COVID-19 has distracted proper care of other illnesses. Herein, we report the impact on new diagnoses of HTLV-1, HTLV-2, and HIV-2 in Spain, where these infections are mostly driven by immigration flows from endemic regions. As expected, case reporting declined for all three retroviral infections with respect to prior years. Furthermore, late presentations were more common. The two major reasons for these observations were significant declines in the arrival of foreigners from endemic regions and a shift in medical resources to prioritize COVID-19.