COVID-19 considerations and strategy for a safe return to international football competitions : an African perspective

The COVID-19 pandemic has affected many aspects of life worldwide—educational, economic, cultural, social and sporting. To limit the spread of COVID-19, initial containment strategies included proper mask wearing, respiratory and hand hygiene, social/physical distancing and different levels of lockdown to limit social interaction. While competitive sport has also been impacted by these measures, risk mitigation protocols have allowed competitions at the national, international and professional levels to resume in some countries around the world. However, additional barriers exist on the African continent to safely resume sport that may not exist elsewhere. These include cost and resource limitations to facilitate player and staff education, safe team transport, hotel and club sanitisation, regular COVID-19 PCR testing with short result turnaround times and access to vaccinations. This commentary outlines practical recommendations for a scientifically valid COVID-19 risk mitigating strategy to enhance safety for teams and spectators at African football competitions that accommodate regional challenges.http://bjsm.bmj.comhj2023Sports Medicin

Virological response and resistance profile in highly treatment-experienced HIV-1-infected patients switching to dolutegravir plus boosted darunavir in clinical practice

Objectives: We evaluated the virological response and resistance profile in combined antiretroviral therapy (cART)-experienced HIV-1-infected patients starting a dual therapy with dolutegravir (DTG) and boosted darunavir (bDRV) for the first time. Methods: Survival analyses were used to evaluate virological success (VS) and virological rebound (VR) in viraemic and virologically suppressed patients, respectively. Major resistance mutations (MRMs) and genotypic susceptibility score (GSS) were evaluated at baseline and after switch. Results: Overall, 130 patients [62 (47.7%) viraemic; 68 (52.3%) virologically suppressed] were retrospectively analysed. At the moment of switch, 81.5% accumulated one or more MRM [protease inhibitor (PI), 35.7%; nucleoside(t)ide reverse transcriptase inhibitor (NRTI), 77.5%; non-NRTI, 69.0%; integrase inhibitor (INI), 10.1%), but 77.7% harboured strains fully susceptible to DTG + bDRV. In viraemic patients, the overall probability of VS by 12 months of treatment was 91.7%. In virologically suppressed patients, the overall probability of VR was 10.5% by 24 months after therapy start. Patients with previous time under virological suppression ≤ 6 months showed a higher VR probability compared with others (37.5% vs. 6.7%, P < 0.002). Among 13 non-responding patients for whom a genotypic resistance test result at failure was available, only two (15.4%) accumulated further resistance in integrase (Y143C/H/R; S147G and N155H) and protease (V32I, L33F, I54L). Conclusions: In highly treatment-experienced patients, the use of dual therapy based on DTG + bDRV appears to be a very good regimen for switch therapy, with a high rate of virological control in both viraemic and virologically suppressed patients. Among non-responding patients, the selection of further resistance is a rare event

Evaluation of HIV-1 integrase variability by combining computational and probabilistic approaches

This study aimed at updating previous data on HIV-1 integrase variability, by using effective bioinformatics methods combining different statistical instruments from simple entropy and mutation rate to more specific approaches such as Hellinger distance. A total of 2133 HIV-1 integrase sequences were analyzed in: i) 1460 samples from drug-naive [DN] individuals; ii) 386 samples from drug-experienced but INI-naive [IN] individuals; iii) 287 samples from INI-experienced [IE] individuals. Within the three groups, 76 amino acid positions were highly conserved (<= 0.2% variation, Hellinger distance: <0.25%), with 35 fully invariant positions; while, 80 positions were conserved (>0.2% to <1% variation, Hellinger distance: <1%). The H12-H16-C40-C43 and D64D116-E152 motifs were all well conserved. Some residues were affected by dramatic changes in their mutation distributions, especially between DN and IE samples (Hellinger distance >= 1%). In particular, 15 positions (D6, S24, V31, S39, L74, A91, S119, T122, T124, T125, V126, K160, N222, S230, C280) showed a significant decrease of mutation rate in IN and/or IE samples compared to DN samples. Conversely, 8 positions showed significantly higher mutation rate in samples from treated individuals (IN and/or IE) compared to DN. Some of these positions, such as E92, T97, G140, Y143, Q148 and N155, were already known to be associated with resistance to integrase inhibitors; other positions including S24, M154, V165 and D270 are not yet documented to be associated with resistance. Our study confirms the high conservation of HIV-1 integrase and identified highly invariant positions using robust and innovative methods. The role of novel mutations located in the critical region of HIV-1 integrase deserves further investigation

Early versus delayed antiretroviral therapy based on genotypic resistance test: Results from a large retrospective cohort study

Rapid start of antiretroviral therapy (ART) pending genotypic resistance test (GRT) has been recently proposed, but the effectiveness of this strategy is still debated. The rate of virological success (VS), defined as HIV-RNA\u2009<\u200950 copies/ml, with and without GRT was compared in drug-na\uefve individuals enrolled in the Italian ARCA cohort who started ART between 2015 and 2018. 521 individuals started ART: 397 without GRT (pre-GRT group) and 124 following GRT (post-GRT group). Overall, 398 (76%) were males and 30 (6%) were diagnosed with AIDS. In the pre-GRT group, baseline CD4+\u2009cell counts were lower (p\u2009<\u20090.001), and viral load was higher (p\u2009<\u20090.001) than in the post-GRT group. The estimated probability of VS in pre-GRT versus post-GRT group was 72.54% (CI95 : 67.78-76.60) versus 66.94% (CI95 : 57.53-74.26) at Week 24 and 92.40% (CI95 : 89.26-94.62) versus 92.92% (CI95 : 86.35-96.33) at Week 48, respectively (p\u2009=\u20090.434). At Week 48, VS was less frequent among individuals with baseline CD4+\u2009cell counts <200 versus >500 (90.33% vs. 97.33%), log viral load <5.00 versus >5.70 log10 cps/ml (97.17% vs 78.16%; p\u2009<\u20090.001), and those treated with protease inhibitors or non-nucleoside reverse transcriptase inhibitors versus those treated with integrase strand transfer inhibitors (p\u2009<\u20090.001). The rate of VS does not seem to be affected by an early ART initiation pending GRT results, but it could be influenced by the composition of the ART regimen, as well as immuno-virological parameters

Baseline integrase drug resistance mutations and conserved regions across HIV-1 clades in Cameroon: implications for transition to dolutegravir in resource-limited settings

Background: Transition to dolutegravir-based regimens in resource-limited settings (RLS) requires prior understanding of HIV-1 integrase variants and conserved regions. Therefore, we evaluated integrase drug resistance mutations (DRMs) and conserved regions amongst integrase strand transfer inhibitor (INSTI)-naive patients harbouring diverse HIV-1 clades in Cameroon. Methods: A cross-sectional study was conducted amongst 918 INSTI-naive patients from Cameroon (89 ART-naive and 829 ART-experienced patients). HIV-1 sequences were interpreted regarding INSTI-DRMs using the Stanford HIVdb v8.9-1 and the 2019 IAS-USA list. Amino acid positions with <1% variability were considered as highly conserved. Subtyping was performed by phylogeny. Results: Overall prevalence (95% CI) of INSTI-DRMs was 0.8% (0.4-1.7), with 0.0% (0.0-4.0) amongst ART-naive versus 0.9% (0.5-1.9) amongst ART-experienced patients; P = 0.44. Accessory mutations (95% CI) were found in 33.8% (30.9-37.0), with 38.2% (28.1-49.1) amongst ART-naive versus 33.4% (30.4-36.7) amongst ART-experienced patients; P = 0.21. Of 288 HIV-1 integrase amino acid positions, 58.3% were highly conserved across subtypes in the following major regions: V75-G82, E85-P90, H114-G118, K127-W132, E138-G149, Q168-L172, T174-V180, W235-A239 and L241-D253. Wide genetic diversity was found (37 clades), including groups M (92.3%), N (1.4%), O (6.2%) and P (0.1%). Amongst group M, CRF02_AG was predominant (47.4%), with a significantly higher frequency (95% CI) of accessory mutations compared with non-AG [41.4% (36.8-46.0) versus 27.1% (23.3-31.2) respectively; P < 0.001]. Conclusions: The low baseline of INSTI-DRMs (<1%) in Cameroon suggests effectiveness of dolutegravir-based regimens. In spite of high conservation across clades, the variability of accessory mutations between major circulating strains underscores the need for monitoring the selection of INSTI-DRMs while scaling up dolutegravir-based regimens in RLS

po 8397 viral suppression among cameroonian adults adolescents and children receiving antiretroviral therapy in the test treat era

BackgroundGlobal efforts in meeting the 90–90–90 targets reveal that 70% of infected people know their HIV status, 77% of these are receiving antiretroviral therapy (ART) and 82% of treated patients have viral suppression. Since launching the 'test and treat' strategy and wider access to drugs that bring down the viral load (VL), evaluating viral suppression would help to identify those requiring interventions and to make progress towards meeting the targets in Cameroon.MethodsA study was conducted from October 2015 to August 2017 amongst adults (≥20 years), adolescents (10–19) and children (0–9) at 12, 24, 36 and ≥48 months on ART, monitored at the Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management (CIRCB) in Yaoundé, Cameroon. VL was established using Abbott m2000RT-PCR. VS was defined as VL <1000 copies/ml; with p<0,05 considered significant.ResultsA total of 1979 patients (70% female) were enrolled (1825 adults, 112 adolescents, 42 children); 1865 were on first-line (NNRTI-based, duration: 48 [IQR 24–48] months) vs. 114 on second-line (PI/r-based, duration: 48 [IQR 36–48] months); with 19%(368) at Month2, 14%(274) at Month24, 10%(207) at Month36% and 54% (1130) at ≥Month48. Overall, viral suppression was 79.4%, and 64.3% had controlled viral replication (VL <40). On first-line, viral suppression was 79.7% (1487) vs. 72.2%(83) on second-line (p=0,076). By ART duration, viral suppression was 83.4%(Month12), 85.8%(Month24), 74.9%(Month36) and 77.3% (≥Month48); p=0,0011. By age-range, viral suppression was 76.2% in children, 54.5% in adolescents, and 80.9% in adults (p<0,0001). By age and ART-regimen, viral suppression on first vs. second line was: children 76.5% vs. 60%; adolescents 51.7% vs. 65.2%; and adults 81.2% vs. 74.7%.ConclusionAbout 80% of Cameroonian patients might be experiencing viral suppression, with a declining performance at adolescence and by 3 years of ART experience. Thus, meeting the viral suppression target by 2020 requires a closer VL monitoring strategy and an adapted adherence support mechanism for adolescents living with HIV in resource-limited settings sharing similar challenges

Evaluation of virological response and resistance profile in HIV-1 infected patients starting a first-line integrase inhibitor-based regimen in clinical settings

Background: Virological response and resistance profile were evaluated in drug-naïve patients starting their first-line integrase inhibitors (INIs)-based regimen in a clinical setting. Study design: Virological success (VS) and virological rebound (VR) after therapy start were assessed by survival analyses. Drug-resistance was evaluated at baseline and at virological failure. Results: Among 798 patients analysed, 38.6 %, 27.1 % and 34.3 % received raltegravir, elvitegravir and dolutegravir, respectively. Baseline resistance to NRTIs, NNRTIs, PIs and INIs was: 3.9 %, 13.9 %, 1.6 % and 0.5 %, respectively. Overall, by 12 months of treatment, the probability of VS was 95 %, while the probability of VR by 36 months after VS was 13.1 %. No significant differences in the virological response were found according to the INI used. The higher pre-therapy viremia strata was (&lt;100,000 vs. 100,000-500,000 vs. &gt; 500,000 copies/mL), lower was the probability of VS (96.0 % vs. 95.2 % vs. 91.1 %, respectively, P &lt; 0.001), and higher the probability of VR (10.2 % vs. 15.8 % vs. 16.6 %, respectively, P = 0.010). CD4 cell count &lt;200 cell/mm3 was associated with the lowest probability of VS (91.5 %, P &lt; 0.001) and the highest probability of VR (20.7 %, P = 0.008) compared to higher CD4 levels. Multivariable Cox-regression confirmed the negative role of high pre-therapy viremia and low CD4 cell count on VS, but not on VR. Forty-three (5.3 %) patients experienced VF (raltegravir: 30; elvitegravir: 9; dolutegravir: 4). Patients failing dolutegravir did not harbor any resistance mutation either in integrase or reverse transcriptase. Conclusions: Our findings confirm that patients receiving an INI-based first-line regimen achieve and maintain very high rates of VS in clinical practice

Virological response and resistance profile in highly treatment‐experienced HIV‐1‐infected patients switching to dolutegravir plus boosted darunavir in clinical practice

Objectives: We evaluated the virological response and resistance profile in combined antiretroviral therapy (cART)-experienced HIV-1-infected patients starting a dual therapy with dolutegravir (DTG) and boosted darunavir (bDRV) for the first time. Methods: Survival analyses were used to evaluate virological success (VS) and virological rebound (VR) in viraemic and virologically suppressed patients, respectively. Major resistance mutations (MRMs) and genotypic susceptibility score (GSS) were evaluated at baseline and after switch. Results: Overall, 130 patients [62 (47.7%) viraemic; 68 (52.3%) virologically suppressed] were retrospectively analysed. At the moment of switch, 81.5% accumulated one or more MRM [protease inhibitor (PI), 35.7%; nucleoside(t)ide reverse transcriptase inhibitor (NRTI), 77.5%; non-NRTI, 69.0%; integrase inhibitor (INI), 10.1%), but 77.7% harboured strains fully susceptible to DTG&nbsp;+&nbsp;bDRV. In viraemic patients, the overall probability of VS by 12&nbsp;months of treatment was 91.7%. In virologically suppressed patients, the overall probability of VR was 10.5% by 24&nbsp;months after therapy start. Patients with previous time under virological suppression&nbsp;≤&nbsp;6&nbsp;months showed a higher VR probability compared with others (37.5% vs. 6.7%, P&nbsp;&lt;&nbsp;0.002). Among 13 non-responding patients for whom a genotypic resistance test result at failure was available, only two (15.4%) accumulated further resistance in integrase (Y143C/H/R; S147G and N155H) and protease (V32I, L33F, I54L). Conclusions: In highly treatment-experienced patients, the use of dual therapy based on DTG&nbsp;+&nbsp;bDRV appears to be a very good regimen for switch therapy, with a high rate of virological control in both viraemic and virologically suppressed patients. Among non-responding patients, the selection of further resistance is a rare event

Predictors of Virological Failure Among People Living with HIV Switching from an Effective First-Line Antiretroviral Regimen

15noneAim of this study was to assess the predictors of virological failure (VF) among patients living with HIV (PLWHIV) switching from an effective first-line antiretroviral therapy (ART) regimen, and to evaluate the emergence of resistance-associated mutations. All adult patients enrolled in the Antiviral Response Cohort Analysis cohort who started ART after 2010, with at least 6 months of virological suppression (VS) before ART switch and with an available genotypic resistance test (GRT) at baseline were included. Thirty-two patients out of the 607 PLWHIV included (5.3%) experienced VF after a median of 11 months from ART switch. Younger age (adjusted Hazard Ratio [aHR] 0.96, 95% confidence interval [CI] 0.92-0.99, p = .023), being male who have sex with male (aHR 0.15, 95% CI 0.03-0.69, p = .014), and longer time from VS to ART switch (aHR 0.97, 95% CI 0.95-1.00, p = .021) resulted protective toward VF, while receiving a first-line regimen containing a backbone other than ABC/3TC or TXF/FTC (aHR 3.61, 95% CI 1.00-13.1, p = .050) and a boosted protease inhibitor as anchor drug (aHR 3.34, 95% CI 1.20-9.28, p = .021) were associated with higher risk of VF. GRT at the moment of VF was available only for 13 patients (40.6%). ART switch in patients with stable control of HIV infection is a safe practice, even if particular attention should be paid in certain cases of patients switching from regimens containing low-performance backbones or protease inhibitors.noneMagnasco, Laura; Pincino, Rachele; Pasculli, Giuseppe; Bouba, Yagai; Saladini, Francesco; Bavaro, Davide Fiore; De Vito, Andrea; Lattanzio, Rossana; Corsini, Romina; Zazzi, Maurizio; Incardona, Francesca; Rossetti, Barbara; Bezenchek, Antonia; Borghi, Vanni; Di Biagio, AntonioMagnasco, Laura; Pincino, Rachele; Pasculli, Giuseppe; Bouba, Yagai; Saladini, Francesco; Bavaro, Davide Fiore; De Vito, Andrea; Lattanzio, Rossana; Corsini, Romina; Zazzi, Maurizio; Incardona, Francesca; Rossetti, Barbara; Bezenchek, Antonia; Borghi, Vanni; Di Biagio, Antoni

Early versus delayed antiretroviral therapy based on genotypic resistance test: Results from a large retrospective cohort study

Introduction: Rapid start of antiretroviral therapy (ART) pending genotypic resistance test (GRT) has been recently proposed, but the effectiveness of this strategy is still debated. Patients and methods: The rate of virological success (VS), defined as HIV-RNA &lt;50 copies/ml, with and without GRT was compared in drug-naïve individuals enrolled in the Italian ARCA cohort who started ART between 2015 and 2018. Results: 521 individuals started ART: 397 without GRT (pre-GRT group) and 124 following GRT (post-GRT group). Overall, 398 (76%) were males and 30 (6%) were diagnosed with AIDS. In the pre-GRT group, baseline CD4+ cell counts were lower (p&lt;0.001), and viral load was higher (p&lt;0.001) than in the post-GRT group. The estimated probability of VS in pre-GRT vs. post-GRT group was 72.54% [CI95: 67.78–76.60] vs. 66.94% [CI95: 57.53–74.26] at week 24 and 92.40% [CI95: 89.26-94.62] vs. 92.92% [CI95: 86.35–96.33] at week 48, respectively (p=0.434). At week 48, VS was less frequent among individuals with baseline CD4+ cell counts &lt;200 vs. &gt;500 (90.33% vs. 97.33%), log viral load &lt;5.00 vs. &gt;5.70 log10 cps/mL (97.17% vs 78.16%) (p&lt;0.001). and those treated with protease inhibitors or non-nucleoside reverse transcriptase inhibitors vs. those treated with integrase strand transfer inhibitors (p&lt;0.001). Conclusions: The rate of VS does not seem to be affected by an early ART initiation pending GRT results, but it could be influenced by the composition of the ART regimen, as well as immuno-virological parameters