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Aim 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

Objectives We evaluated the HIV-1 capsid genetic variability and lenacapavir drug resistance-associated mutations (DRMs) among drug-naive individuals across HIV-1 clades. Methods A total of 2031 HIV-1 sequences from drug-naive patients were analysed for capsid amino acid modification and the prevalence of lenacapavir DRMs. Amino acid positions with Results Overall, 63% (148/232) of amino acid positions were conserved in the capsid protein. Of note, conservation was consistent in specific binding residues of cellular factors involved in viral replication [CypA (G89, P90), CPSF6 (Q4, N57, N74, A77, K182) and TRIM-NUP153 (R143)], while N183 (12.31%) was the only non-conserved lenacapavir binding residue. The overall prevalence (95% CI) of lenacapavir DRMs was 0.14% (0.05–0.44) (3/2031), with M66I (0.05%) and Q67H (0.05%) observed in subtype C, and T107N (0.05%) observed in CRF01_AE. Moreover, polymorphic mutations M66C (n = 85; 4.18%), Q67K (n = 78; 3.84%), K70R (n = 7; 0.34%), N74R (n = 57; 2.81%) and T107L (n = 82; 4.03%) were observed at lenacapavir resistance-associated positions. Conclusions The low level of lenacapavir DRMs (

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 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. 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 0.001), and viral load was higher (p 0.001) than in the post-GRT group. The estimated probability of VS in pre-GRT versus post-GRT group was 72.54% (CI

Objectives We evaluated natural resistance to the new antiretroviral fostemsavir and its potential association with other HIV-1 gp120 polymorphisms. Methods A total of 1997 HIV-1 B subtype gp120 sequences from the Los Alamos HIV Database were analysed for mutation prevalence at fostemsavir resistance-associated positions and potential association with other gp120 polymorphisms. The role of each fostemsavir resistance-related position and the correlated gp120 mutations, both in protein stability and in reducing the binding affinity between antibody and/or T cell lymphocyte epitopes and the MHC molecules, was estimated. Results The prevalence of fostemsavir resistance mutations was as follows: L116Q (0.05%), S375H/M/T (0.55%/1.35%/17.73%, the latter being far less relevant in determining resistance), M426L (7.56%), M434I (4.21%) and M475I (1.65%). Additionally, the M426R polymorphism had a prevalence of 16.32%. A significantly higher prevalence in X4 viruses versus R5 viruses was found only for S375M (0.69% versus 3.93%, P = 0.009) and S375T (16.60% versus 22.11%, P = 0.030). Some fostemsavirv resistance positions positively and significantly correlated with specific gp120 polymorphisms: S375T with I371V; S375M with L134W, I154V and I323T; M475I with K322A; and M426R with G167N, K192T and S195N. The topology of the dendrogram suggested the existence of three distinct clusters (bootstrap ≥0.98) involving these fostemsavir resistance mutations and gp120 polymorphisms. Interestingly, all clustered mutations are localized in class I/II-restricted T cell/antibody epitopes, suggesting a potential role in immune HIV escape. Conclusions A low prevalence of known fostemsavir resistance mutations was found in the HIV-1 B subtype. The detection of novel HIV-1 gp120 polymorphisms potentially relevant for fostemsavir resistance deserves new in-depth in vitro investigations.

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-naïve [DN] individuals; ii) 386 samples from drug-experienced but INI-naïve [IN] individuals; iii) 287 samples from INI-experienced [IE] individuals. Within the three groups, 76 amino acid positions were highly conserved (0.2% to =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.

Background COVID-19 has been the most important public health concern worldwide since 2020. Several vaccines are now available to help in controlling COVID-19 associated morbidity and mortality. This study will aim to provide the global and regional prevalence of SARS-CoV-2 infection as well as an estimate of disease severity among COVID-19 vaccinated individuals. Materials and methods In order to determine the global burden of SARS-CoV-2 infection among vaccinated individuals, we will systematically extract and review papers from PubMed/MEDLINE, Excerpta Medica database (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), Science direct and Cumulative Index to Nursing and Allied Health Literature (CINAHL). All the studies describing the prevalence and/or disease severity (hospitalization and case fatality rate) data of COVID-19 among individuals who received a partial or complete dose of WHO-approved COVID-19 vaccines will be eligible. A random effect model will be used to calculate the pooled prevalence and to estimate the disease severity. Subgroup analysis will be performed to explore the association between the number of vaccine doses received and the COVID-19 burdens. Discussion This systematic review and meta-analysis will provide the global estimate data on pooled prevalence, hospitalization and case fatality rates of COVID-19 among vaccinated individuals. Moreover, the factors associated with reinfection and disease severity will be equally investigated in the meta-analysis. The results of this study will contribute in the understanding and estimation of the global burden of COVID-19 among vaccinated individuals. Findings will provide meaningful information for the success of the current global rollout of COVID-19 vaccination strategies and pave the way for future interventions. Systematic review registration CRD42021273074.

Response to ritonavir-boosted-protease inhibitors (PI/r)-based regimen is associated with some Gag mutations among HIV-1 B-clade. There is limited data on Gag variants and their covariation with mutations in protease among HIV-1 non-B-clades at PI/r-based treatment failure. Thus, we characterized Gag variants present in isolates from HIV-1 infected individuals treated to a PI/r-regimen (n=143) and compared them to those obtained from individuals not treated to PI/r (ART-naïve [n=101] or RTI-treated [n=118]). The most frequent HIV-1 subtypes were CRF02_AG (54.69%), A (13.53%), D (6.35%) and G (4.69%). Eighteen Gag variants (distributed in three groups) showed a significantly higher prevalence in PI/r-treated isolates compared to ART-naïve (p

ObjectivesTo evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options.MethodsHIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) values. Cumulative resistance and drug activity were evaluated by Stanford algorithm.ResultsOverall, median (IQR) CD4 count (cells/mm3) nadir and at last genotypic resistance test (GRT) available were 98 (33–211) and 312 (155–517), respectively. Considering HIV-1 tropism, 30.5% had X4/dual-mixed strains (FPR ≤5%: 22.2%; FPR 5%–10%: 8.3%). By stratifying according to tropism, by decreasing FPR, a significant decrease of CD4 nadir and at last GRT was observed. The proportion of individuals with CD4 count ConclusionsOur findings showed that a small proportion of cART failing individuals have limited therapeutic options. However, tropism determination might help to identify people who have accumulated a high level of resistance and have a greater risk of advanced disease.

Scientometrics enables scholars to assess and visualize emerging research trends and hot-spots in the scientific literature from a quantitative standpoint. In the last decades, Africa has nearly doubled its absolute count of scholarly output, even though its share in global knowledge production has dramatically decreased. The still-ongoing COVID-19 pandemic has profoundly impacted the way scholarly research is conducted, published, and disseminated. However, the COVID-19-related research focus, the scientific productivity, and the research collaborative network of African researchers during the ongoing COVID-19 pandemic remain to be elucidated. This study aimed to clarify the COVID-19 research patterns among African researchers and estimate the strength of collaborations and partnerships between African researchers and scholars from the rest of the world during the COVID-19 pandemic, collecting data from electronic scholarly databases such as Web of Science (WoS), PubMed/MEDLINE and African Journals OnLine (AJOL), the largest and prominent platform of African-published scholarly journals. We found that COVID-19-related collaboration patterns varied among African regions. For instance, most of the scholarly partnerships occurred with formerly colonial countries (such as European or North-American countries). In other cases, scholarly ties of North African countries were above all with the Kingdom of Saudi Arabia. In terms of number of publications, South Africa and Egypt were among the most productive countries. Bibliometrics and, in particular, scientometrics can help scholars identify research areas of particular interest, as well as emerging topics, such as the COVID-19 pandemic. With a specific focus on the still-ongoing viral outbreak, they can assist decision- and policy-makers in allocating funding and economic-financial, logistic, organizational, and human resources, based on the specific gaps and needs of a given country or research area.

Background: More than one year after the beginning of the international spread of COVID- 19, the reasons explaining its apparently lower reported burden in Africa is still to be fully elucidated. Few studies previously investigated the potential reasons explaining this epidemiological observation using data at the level of a few African countries. However, an updated analysis considering the various epidemiological waves and variables across an array of categories, with a focus on African countries might help to better understand the COVID-19 pandemic on the continent. Thus, we investigated the potential reasons for the persistently lower transmission and mortality rates of COVID-19 in Africa. Methods: Data were collected from publicly available and well-known online sources. Cumulative numbers of COVID-19 cases and deaths per one million population reported by African countries up to February 2021 were used to estimate the transmission and mortality rates of COVID-19, respectively. Covariates were collected across several data sources: clinical/diseases data, health system performance, demographic parameters, economic indicators, climatic, pollution and radiation variables, and use of social media. Collinearities were corrected using variance inflation factor (VIF) and selected variables were fitted to a multiple regression model using the R statistical package. Results: Our model (adjusted R-squared: 0.7) found that the number of COVID-19 tests per one million population, GINI index, global health security (GHS) index and mean body mass index (BMI) were significantly associated (P

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

Virological response and resistance profile were evaluated in drug-naïve patients starting their first-line integrase inhibitors (INIs)-based regimen in a clinical setting.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.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 (100,000 vs. 100,000-500,000 vs.500,000 copies/mL), lower was the probability of VS (96.0 % vs. 95.2 % vs. 91.1 %, respectively, P0.001), and higher the probability of VR (10.2 % vs. 15.8 % vs. 16.6 %, respectively, P = 0.010). CD4 cell count200 cell/mmOur findings confirm that patients receiving an INI-based first-line regimen achieve and maintain very high rates of VS in clinical practice.

ObjectivesTo evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy.MethodsDynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999–2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm).ResultsAmong 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P ConclusionsA dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.

Background Thrombocytopenia is an abnormal decrease in blood platelets, which can affect the prognosis of people living with HIV (PLHIV). In order to limit the occurrence of this haematological disorder, we evaluated the frequency of thrombocytopenia according to antiretroviral drug combinations, viremia and the immune status of PLHIV. Methods A cross-sectional and analytical study was conducted from June-November 2016 among 310 PLHIV at the “Chantal BIYA” International Reference Centre for research on HIV/AIDS prevention and management (CIRCB), Yaoundé, Cameroon. Thrombocytopenia was assessed by blood count on Mindray BC 3000 plus, then categorized as mild (50,000-149,999 platelets/μL), moderate (20,000-49,999) and severe 3log10 RNA/ml. Overall rate of thrombocytopenia was 19.0% (59/310), with 17.4% (54/310) mild, 1.6% (5/310) moderate and 0.0% severe. Following ART-exposure, rate of thrombocytopenia was 64.6% (42/65) versus 6.9% (17/245) in naïve versus treated patients respectively, p3 log10 RNA/ml (p=0.03; r=-0.12). As concerns CD4-count, rate of thrombocytopenia was 16.2% (42/259) in those with ≥200 CD4/mm3 versus 33.3% (17/51) with