HIV Drug Resistance Research Articles

HIV-1 drug resistance and genetic transmission networks among patients with sexually transmitted HIV in Ningxia, China

BackgroundOver the past decade, sexual transmission has become a dominant source of new HIV-1 infection in China. However, very few studies have been conducted to characterize the two sexual transmissions, homosexual and heterosexual transmission. This study was conducted to better understand the relationship between genotypes, drug resistance, and molecular transmission networks in two groups of sexually transmitted HIV-1 in Ningxia, China.MethodsPlasma samples were collected from sexually transmitted HIV/AIDS patients in Ningxia between 2020 and 2021 for RNA extraction followed by HIV-1 genome sequencing, genotype and drug resistance analyses. The TN93 model in HyPhy2.2.4 with 1.25% as the threshold, was used to calculate the gene distance, and Cytoscape3.7.0 was used to generate a visual molecular transmission network.ResultsA total of 269 samples were successfully sequenced, and 10 HIV-1 subtypes were detected. The two most common subtypes were CRF07_BC and CRF01_AE. All 10 subtypes were detected in heterosexually transmitted patients, and 7 subtypes were found in homosexually transmitted patients who were exclusively men sex with men (MSM). The drug resistance rates of heterosexual individuals and MSMs were 45.34 and 33.33%, respectively. Sequences from 120 patients entered the molecular transmission network, forming 35 clusters. The clustering rate for MSM (52.78%) was higher than that of heterosexual individuals (39.13%). Some MSM and HSTs were involved in the same cluster and might act as bridges for transmission between the two populations.ConclusionOur data showed that heterosexually transmitted HIV-1 was more likely to be a drug-resistant virus, whereas MSM was more likely to contract viruses through network connection. It is strongly recommended that resistance testing be conducted before ART to improve effective treatment and reduce the spread of resistant viruses. Molecular networks can help to identify transmission clusters and provide more precise interventions.

Incompletely closed HIV-1CH040 envelope glycoproteins resist broadly neutralizing antibodies while mediating efficient HIV-1 entry

HIV-1 envelope glycoproteins (Envs) mediate viral entry and are sole target of neutralizing antibodies. Thus, HIV-1 Envs must maintain a delicate balance between evading neutralizing antibodies while still preserving viral compatibility to mediate entry into target cells. Here, we studied the viral entry effeciency, fitness, and replication of an incompletely closed, transmitted/founder HIV-1 Envs (CH040), which are highly resistant to most bnAbs. CH040 Envs mediated HIV-1 entry to target cells as efficient as other primary Envs, suggesting that antibody resistance and efficient viral entry can develop independently. Expression of CH040 Envs was comparable to other Envs and most CH040 variants that were rationally engineered to increase bnAb resistance showed no significant decrease in their ability to mediate HIV-1 entry. We detected robust in vitro spread of SHIV CH040 in pig-tailed macaque lymphocytes that was comparable to efficient spread of other SHIVs. Our study provides insights into the relationship between bnAb resistance and efficient HIV-1 entry.

HIV Drug Resistance Profile in Clients Experiencing Treatment Failure After the Transition to a Dolutegravir-Based First-Line Antiretroviral Treatment Regimen in Mozambique

Real-world data on HIV drug resistance (HIVDR) after transitioning to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) are limited. We assessed HIVDR rates and patterns in clients with virological failure (VF) after switching from an NNRTI-based regimen to TLD. A cross-sectional study was conducted in Gaza, Mozambique (August 2021–February 2022), including adults on first-line ART for ≥12 months who transitioned to TLD and had unsuppressed viral load (VL) ≥ 1000 copies/mL six months post-transition. After three adherence counseling sessions, participants with VF underwent genotyping for drug resistance mutations (DRMs) using the Stanford HIVdb Program. Of 717 participants (median age 39.2 years, 70.7% female), 217 (30.2%) had VF, 193 (88.9%) underwent genotyping, with 183 (94.8%) successfully genotyped. Intermediate–high dolutegravir (DTG) resistance was found in 19.6% (36/183). Unsuppressed VL before DTG transition was independently associated with VF (aOR: 2.14). Resistance patterns included 33.3% (12/36; 95% CI: 14.6–46.3) to all three TLD drugs, 55.6% (20/36; 95% CI: 39.3–71.9) to DTG and 3TC, and 11% (4/36; 95% CI: 0.8–21.3) to DTG only. Major drug resistance mutations to DTG included G118R (9.3%), R263K (6.6%), and Q148H/R/K (4.4%). This study highlights the need to consider virologic status before transitioning PLHIV to TLD and suggests that adherence counseling may not prevent resistance in those with unknown or prior VF.

Detection of Antiretroviral Drug-Resistant Mutations and HIV-1 Subtypes in Circulation Among Men Who Have Sex With Men, SEM Females, and Female Sex Workers: Results of Vietnam's HIV Sentinel Surveillance Plus System, 2018-2020.

HIV drug resistance can reduce the effectiveness of antiretroviral drugs in preventing morbidity and mortality, limit options for treatment, and prevention. Our study aimed to assess HIV-1 subtypes and HIV drug resistance among key populations in HIV Sentinel Surveillance Plus Behavior in 2018 and 2020. One-stage venue-based cluster sampling was used to recruit participants at hotspots identified for men who have sex with men (MSM) in 7 provinces and sexual minority females and female sex workers (FSW) in 13 provinces. Participants completed a standard questionnaire about risk and preventive behaviors, and antiretroviral therapy history, and provided intravenous blood for HIV testing. HIV drug resistance testing was conducted on HIV-positive samples with viral load >1000 copies/mL. A total of 185 of 435 (42.5%) HIV-positive samples had viral load ≥1000 copies/mL, of which 130 of 136 from MSM and 26 of 49 from FSW were successfully sequenced. Six HIV-1 subtypes were detected (CRF01_AE, A, CRF07/08_BC, B, C, CRF25_cpx), with CRF01_AE (82.7%, 129/156) the most common. Drug resistance mutations were detected in 16.7% of participants overall (26/156), in 15.4% (20/130) of MSM, and in 23.1% (6/26) of FSW. Mutations associated with resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) were the most frequently detected (73.1%, 19/26). The high level of resistance was presented in NNRTI and nucleoside reverse transcriptase inhibitors classes. There are 10 major resistance mutations detected with nucleoside reverse transcriptase inhibitors (M184VI-25.0%, K65KR-50.0%, Y115F-25%), NNRTI (K103N-21.1%, E138A-10.5%, V106M-5.3%, K101E-5.3%, G190A-5.3%), protease inhibitors (L33F-40.0%, M46L-20.0%). Vietnam's HIV Sentinel Surveillance Plus system identified an emerging strain of HIV-1 and mutations associated with resistance to multiple drug classes among MSM and FSW.

Pretreatment HIV Drug Resistance to Integrase Strand Transfer Inhibitors Among Newly Diagnosed HIV Individuals — China, 2018–2023

Pretreatment HIV Drug Resistance to Integrase Strand Transfer Inhibitors Among Newly Diagnosed HIV Individuals — China, 2018–2023

VLPs Carring HIV-1 Env with Modulated Glycan Composition

Previously obtained highly immunogenic Env-VLPs ensure overcoming the natural resistance of HIV-1 surface proteins associated with their low level of incorporation and inaccessibility of conserved epitopes to induce neutralizing antibodies. We also adopted this technology to modify Env trimers of ZM53(T/F) strain to produce Env-VLPs by recombinant vaccinia viruses (rVVs). These rVVs expressing Env, Gag-Pol (HIV-1/SIV), as well as the cowpox virus hr gene allowing to avoid the restriction of vaccinia virus replication in CHO cells were used for VLP production. The CHO Lec1 engineered cell line lacking GlcNAc-TI was used for generating VLPs with Env proteins containing a cytoplasmic domain (CT) affecting on surface subunit (SU) conformation. This has created the opportunity to modulate the glycan composition, and refine the conditions for their production, and optimize approaches to overcoming HIV-1 resistance associated with abundant glycosylation.

Major role of dolutegravir in the emergence of the S147G integrase resistance mutation.

The S147G mutation is associated with high-level resistance to the integrase strand transfer inhibitor (INSTI) elvitegravir. In several poorly documented cases, it was also selected in patients on dolutegravir. Given the widespread use of dolutegravir, further studies of S147G are required. We consulted the HIV-1 resistance databases of French laboratories to identify all cases of S147G emergence. We collected immunological and virological parameters, history of treatment and INSTI resistance mutations. Mann-Whitney and Fisher's exact tests were performed. We retrospectively identified 88 cases of S147G selection, from 2015 to 2022, in 22 laboratories. The most frequent HIV-1 subtypes were Clade B (55.7%) and CRF02_AG (21.6%). At the time of resistance genotyping, the median viral load was 5860 copies/mL (IQR 1011-24 525) and the median CD4 cell count was 412 cells/mm3 (228-560). S147G emerged on dolutegravir (48%), elvitegravir (36%) and raltegravir (10%) treatments. S147G was associated with a larger median number of other INSTI mutations on dolutegravir than on elvitegravir [3.0 (2.0-4.0) versus 2.0 (1.0-2.0); P = 0.0002] and was never observed with G148H or G118R. On dolutegravir, S147G was associated principally with T97A (62%), N155H (59%), E138K (50%), L74I/M (38%) and Q148R (33%). In this French study, S147G emerged principally in patients on dolutegravir regimens, in association with up to five other INSTI resistance mutations. This accumulation of mutations suggests a replicative advantage on HIV strains under dolutegravir selection pressure, suggesting that caution is required when interpreting dolutegravir resistance in the presence of such S147G resistance patterns, even in patients prescribed dolutegravir twice daily.

Two-fold increased risk of cardiovascular events in people with MDR HIV: a matched cohort analysis with data from the PRESTIGIO registry.

Major adverse cardiovascular events (MACEs) may contribute to the high morbidity in people with four-class drug-resistant HIV (4DR-PWH). To explore the probability of MACEs in 4DR-PWH compared with non-4DR controls. This was a retrospective, propensity score-matched cohort study on 4DR-PWH (cases) and non-4DR-PWH (controls), on ART, without previous MACEs. Controls were matched with cases in a 4:1 ratio for age, sex-assigned-at-birth and ART duration. Incidence rates (IRs) and incidence rate ratio (IRR) of MACEs with 95% CIs were modelled by Poisson regression. Cumulative probabilities of the first incident MACE were estimated by Kaplan-Meier curves. A multivariable stepwise Cox proportional hazards model estimated predictors of incident MACEs among covariates with univariable P < 0.100. Overall, 223 4DR-PWH and 797 non-4DR-PWH were evaluated. During a median (IQR) follow-up of 8.2 (5.4-11.1) years [1833 person-years of follow-up (PY)], 23/223 (10.3%) 4DR-PWH developed 29 MACEs, IR = 1.6 (95% CI = 1.1-2.3)/100 PY. During a median follow-up of 8.4 (5.2-11.0) years (6450 PY), 42/797 (5.3%) non-4DR controls had 45 MACEs, IR = 0.7 (95% CI = 0.5-0.9)/100 PY, IRR (4DR/non-4DR) = 2.3 (95% CI = 1.4-3.6). The cumulative probabilities of the first MACE were more than doubled in 4DR-PWH (P = 0.006). At multivariable analysis, an increased risk of MACEs was associated with 4DR status [adjusted hazard ratio (aHR) = 1.9; 95% CI = 1.0-3.4], after adjusting for age, sex-assigned-at-birth, HIV load, CD4+ nadir, total cholesterol, HDL cholesterol, diabetes mellitus, statin use and baseline HCV serostatus. In PWH, MDR is significantly associated with a higher risk of cardiovascular events. Prompt implementation of prevention strategies is mandatory in this fragile population.

In-silico ADMET and molecular docking evaluation of an active cyclopeptide from a Saharan Streptomyces strain with anticancer, anti-HIV, and anti- SARS-CoV-2 activities

The emergence of new SARS-CoV-2 variants, HIV drug resistance, and the persistent burden of breast cancer have created an urgent need to identify new antiviral and anticancer drug candidates. In this investigation, we employed in-silico methods to evaluate the pharmacokinetic proprieties and toxicity, and the inhibitory potential of a cyclic peptide compound produced by a novel Streptomyces strain using target enzymes. In silico analysis of the ADMET profile indicates that the cyclic peptide cyclo(L-pro-L-tyr) has favorable physicochemical properties, good lipophilicity and water solubility, generally favorable pharmacokinetic characteristics, and low toxicity for the cyclic peptide. In addition, the docking studies of the compound showed strong binding affinities with HIV-1 integrase at -7.4 kcal/mol, HIV-1 reverse transcriptase at -8.1 kcal/mol, COVID-19 main protease at -8.5 kcal/mol, and SARS-CoV-2 spike glycoprotein at -7.7 kcal/mol compared to references inhibitors. Furthermore, it has a good binding affinity with estrogen receptor alpha associated with breast cancer at -6.8 kcal/mol compared to reference inhibitors. Therefore, the findings demonstrate the potential of cyclo(L-pro-L-tyr) as a novel bioactive compound with antiviral and anticancer properties. This means that it needs to be tested in more experiments and further developed as a lead compound for treating SARS-CoV-2 infections, HIV/AIDS, and breast cancer.

HIV/AIDS KNOWLEDGE IMPROVES ANTIRETROVIRAL DRUG COMPLIANCE

Antiretroviral (ARV) therapy compliance is very important for people living with HIV/AIDS (PLWHA) and their support group. Effective ARV medication was essential for HIV infected patients to improve their health, reduce progression, reduce HIV drug resistance, prolong patient life expectancy, and decrease risk of HIV/AIDS transmission to others. Many factors caused non-adherence to ARV drugs. This study aimed to determine the relationship between education, HIV/AIDS knowledge level and ARV compliance. This study was cross-sectional design using consecutive non-random sampling with total sample of 34 subjects. Data were collected using questionnaire. The number of subject conducted in Public Heatlh Center of Cibatu District, Cikarang, Indonesia from October to November 2018. Chi-Square and Fisher test was used to analysed data. Most of the respondents were males, 20-25 years old, intermediate education, HIV/AIDS knowledge level was high, and had good ARV compliance level. There was a significant relationship between education, HIV/AIDS knowledge and ARV medication compliance.

Heavily treatment-experienced patients with HIV: are new mechanisms of action enough?

Antiretroviral (ARV) drug resistance poses a threat to ending the HIV epidemic. As the rates of integrase resistance continue to increase globally, the availability of options for HIV treatment becomes limited. Heavily treatment-experienced (HTE) people with HIV (PWH) are limited to two or fewer available fully active ARV classes and are more likely to have an AIDS-defining event. Appropriate identification and management of HTE PWH is crucial to improving patient outcomes and reducing the future spread of drug-resistant HIV. As treatment options become more limited owing to drug resistance, the availability of more potent drugs with a marked increase in virologic suppression is needed in the current ART era. The purpose of this narrative review is to review the identification of HTE PWH, novel mechanisms of resistance, and management of HTE PWH in resource-rich and resource-limited settings using novel ARVs and combination ART.

EE621 Treatment Cost of Heavily Treatment-Experienced Adult Patients With Multi-Drug Resistant HIV-1 Infection in Brazil

EE621 Treatment Cost of Heavily Treatment-Experienced Adult Patients With Multi-Drug Resistant HIV-1 Infection in Brazil

Long Noncoding RNA LINC02453 Inhibits HIV-1 Replication by Binding With SEC13 to Regulate the Viral Productive Cycle.

Emerging evidence underscores the pivotal role of long noncoding RNAs (lncRNAs) as crucial regulators within the HIV life cycle. However, the precise functions and detailed mechanisms by which lncRNAs operate in HIV-1 highly exposed but persistently seronegative (HESN) individuals remain currently unknown. Through RNA sequencing analysis of the HESN individual and the matched control, we identified potential lncRNAs. Then, we conducted validation experiments at the population level, while cellular models of HIV-1 infection were constructed for functional experimental investigations in vitro. Subcellular localization of the identified lncRNA was determined, followed by an exploration of the specific regulatory mechanism underlying HIV resistance through some experiments, such as RNA pull-down, western blot and Hirt assays. LncRNA LINC02453 is highly expressed in HESN. Moreover, LINC02453 is identified as a novel lncRNA associated with heightened resistance to HIV-1. LINC02453 is predominantly localized in the nucleus and binds to SEC13, a component of the nuclear pore complex, leading to the inhibition of HIV-1 replication by regulating key processes such as late reverse transcription, nuclear import, and DNA integration. Our findings suggest that LINC02453 may serve as a prospective target for the development of innovative anti-HIV therapeutics.

Next-generation sequencing and drug resistance mutations of HIV-1 subtypes in people living with HIV in Sicily, Italy, 2021-2023.

HIV-1 infection continues to be a significant public health concern, notwithstanding the expanded utilization of antiretroviral treatment (ART), due to the emergence of drug resistance. The prevalence of transmitted drug resistance remains uncertain, particularly concerning integrase inhibitors. This study aimed to assess the extent of HIV resistance in both ART-naïve and experienced individuals living with HIV (PLHIV) at the University Hospital in Palermo, Italy. Genotyping and mutation analysis were performed on ART naïve and experienced PLHIV admitted from June 2021 to October 2023 by the NGS method. Mutations were detected by testing different NGS frequency cut-offs: ≥5%, ≥10%, and ≥20%. Demographic, clinical, virological, and immunological data were retrospectively collected. Of the PLHIV, 85 (70%) were ART-naïve, while 36 (30%) were ART-experienced with virological failure. The main HIV-1 subtype was B (54%), which was significantly associated with Italy-born (p < 0.001) and experienced PLHIV (p = 0.024). In the remaining cases, A1 (6%), C (3%), F1 (7%), G (2%), and Circulating Recombinant Forms (28%) were reported. At least one mutation for a drug class was detected in 39.7%, 45.4%, and 53.7% of cases at HIV-1 NGS thresholds of 20%, 10%, and 5%, respectively. Drug resistance was found in 18.2%, 25.6%, and 33.0%, by NGS cut-off of 20%, 10%, and 5 % respectively. The lowering of NGS cut-offs mainly increased the rates of integrase strand transfer inhibitor resistance. For overall resistance, no difference was observed between B and non-B subtypes for any NGS cut-offs.

Neuropathy among drug resistant HIV Patients treated in Jakarta

Introduction: Some people living with HIV (PLWH) receiving ART in Indonesia display poor clearance of replicating virus. This has been associated with HIV-associated sensory neuropathy. Here we assess whether treatment failure reflects the presence of drug resistance mutations. Methodology: PLWH were stratified by HIV RNA levels using a ≥ 1000 copies/mL cut-off after 5.3 (2-7.5) years on ART. Drug-resistance mutations were analyzed in seven of ten cases with a detectable viral load. The HIV pol gene was screened for mutations affecting resistance to nucleoside inhibitors (NRTI), non-nucleoside inhibitors (NNRTI) and protease inhibitors (PI). We recorded co-infections, transmission routes, and neuropathy based on the Brief Peripheral Neuropathy Screen Tool. Results: The primary HIV subtype was HIV-1 CRF01_AE, but one patient had subtype G. Polymorphisms affecting NRTI or NNRTI (6/7 cases) and protease inhibitors (1/7 cases) were identified. Three mutations affecting NRTI (M184V, M4IL, T215F), two for NNRTI (K103N, G190A) and five for protease inhibitors (M46I, I50V, I54V, V82A, N88NDGS) were evident. Subjects with resistance mutations were mostly intra-venous drug users (4/7) and had a higher risk of neuropathy (p = 0.016). Conclusions: Drug resistance mutations were present in most cases of treatment failure examined and were therefore indirectly a risk factor for peripheral neuropathy.

HIV-2 drug resistance genotyping and viral load among HIV-2 infected adults in Burkina Faso, West Africa.

HIV-2 infection although less virulent compared to HIV-1 is endemic in many parts of West Africa. In Burkina Faso, few data exist on HIV-2 genotypic resistance. The objective of this study was to assess HIV-2 genotypic resistance and viral load in adult patients infected with HIV-2 in Burkina Faso. This was a cross-sectional study that ran from February 2017 to March 2019. This study included 91 HIV-infected adult patients on ARV treatment. HIV and hepatitis B and C status were confirmed by serological tests. HIV-2 viral load and HIV-2 clusters were determined by in-house tests. The mean age was 58.99 ±8.66 years. Of the patients, 12.1% were HIV-1, 73.6% were HIV-2 and 14.3% were co-infected with HIV-1/HIV-2. Only 15% had a high viral load (more than 1000 copies/mL). Groups A and B were detected in this study with the majority being group A (23.75%). HIV-2 subtype CRF01_AB was found in 3.75% of HIV-2 patients. Of the 34 HIV-2 patients whose subtypes were determined, only 7 had reverse transcriptase and 3 had protease resistance mutations. The M184V mutation was the most detected. This study revealed recent data on the status of HIV-2 genotypic resistance in Burkina Faso. Although few HIV-2 infected patients on ARV treatment have developed resistance, it is important to establish a surveillance system for HIV-2 genotypic resistance.

Multiple third-generation recombinants formed by CRF55_01B and CRF07_BC in newly diagnosed HIV-1 infected patients in Shenzhen city, China

In the evolution landscape of HIV, the coexistence of multiple subtypes has led to new, complex recombinants, posing public health challenges. CRF55_01B, first identified among MSM in Shenzhen, China, has spread rapidly across China. In this study, 47 plasma samples from newly diagnosed HIV-1 CRF55_01B patients in Shenzhen, of which the genotype was only identified by the routine HIV drug resistance test, were collected. Multiple gene regions were acquired using Sanger and next-generation sequencing methods, followed by the phylogenetic reconstruction, recombination breakpoint scanning, Bayesian molecular clock, and the prediction of coreceptors. From 47 samples, we found seven new unique recombinants formed by CRF55_01B and CRF07_BC, which shared similar breakpoints in certain gene regions and primarily utilized CCR5 receptors. All of the most recent common ancestors of subregions for these recombinants were estimated to be later than CRF55_01B and CRF07_BC, potentially suggesting they are the third-generation recombinants formed by CRF55_01B and CRF07_BC as parents. The continuous emergence of new recombinants highlights the increasing complexity of circulating strains in Shenzhen, and also suggests that subtype analysis using partial pol gene may lead to an overestimation of the major subtype strains and an underestimation of new complex HIV recombinants. Consequently, to effectively address and mitigate the complex HIV epidemic, there is an urgent need for expanded monitoring and the optimization of testing methodologies.

Structural and Mechanistic Bases for Resistance of the M66I Capsid Variant to Lenacapavir.

Lenacapavir (LEN) is a highly potent and long-acting antiretroviral that works by a unique mechanism of targeting the viral capsid protein. The inhibitor is used in combination with other antiretrovirals to treat multi-drug-resistant HIV-1 infection in heavily treatment-experienced adults. Furthermore, LEN is in clinical trials for preexposure prophylaxis (PrEP) with interim results indicating 100 % efficacy to prevent HIV-1 infections. However, one notable shortcoming is a relatively low barrier of viral resistance to LEN. Clinical trials and cell culture experiments identified emergent resistance mutations near the inhibitor binding site on capsid. The M66I variant was the most prevalent capsid substitution identified in patients receiving LEN to treat muti-drug resistant HIV-1 infections. The studies described here elucidate the underlying mechanism by which the M66I substitution confers a marked resistance to the inhibitor. Furthermore, our structural findings will aid future efforts to develop the next generation of capsid inhibitors with enhanced barriers to resistance.

Booster-free anti-retroviral therapy for persons living with HIV and multidrug resistance (B-Free): protocol for a multicentre, multistage, randomised, controlled, non-inferiority trial

IntroductionAnti-retroviral therapy (ART) simplification strategies are needed for treatment-experienced people with HIV (PWH) and multidrug-resistant viruses. These individuals are commonly treated with boosted ART regimens and are thereby at risk...

Learning patterns of HIV-1 resistance to broadly neutralizing antibodies with reduced subtype bias using multi-task learning.

The ability to predict HIV-1 resistance to broadly neutralizing antibodies (bnAbs) will increase bnAb therapeutic benefits. Machine learning is a powerful approach for such prediction. One challenge is that some HIV-1 subtypes in currently available training datasets are underrepresented, which likely affects models' generalizability across subtypes. A second challenge is that combinations of bnAbs are required to avoid the inevitable resistance to a single bnAb, and computationally determining optimal combinations of bnAbs is an unsolved problem. Recently, machine learning models trained using resistance outcomes for multiple antibodies at once, a strategy called multi-task learning (MTL), have been shown to improve predictions. We develop a new model and show that, beyond the boost in performance, MTL also helps address the previous two challenges. Specifically, we demonstrate empirically that MTL can mitigate bias from underrepresented subtypes, and that MTL allows the model to learn patterns of co-resistance to combinations of antibodies, thus providing tools to predict antibodies' epitopes and to potentially select optimal bnAb combinations. Our analyses, publicly available at https://github.com/iaime/LBUM, can be adapted to other infectious diseases that are treated with antibody therapy.