Jorge Sanchez

• Aston University

Background Decentralizing HIV services is an evidence-based strategy recommended by the World Health Organization to expand healthcare access by shifting most HIV care from specialty (SHCs) to primary health centers (PHCs) with the goal of maximizing health outcomes. To accelerate Peru Ministry of Health’s 2020 priority to transition from specialty...

The Aedes aegypti cadherin-like protein (Aae-Cad) and the membrane-bound alkaline phosphatase (Aae-mALP) are membrane proteins identified as putative receptors for the larvicidal Cry toxins produced by Bacillus thuringiensis subsp. israelensis bacteria. Cry toxins are the most used toxins in the control of different agricultural pest and mosquitos....

Bacillus thuringiensis (Bt) produces crystals composed mainly of Cry pesticidal proteins with insecticidal activity against pests but are highly susceptible to degradation by abiotic factors. In this sense, encapsulation techniques are designed to improve their performance and lifetime. However, the effects of polymeric matrix encapsulation such as...

Background Injectable cabotegravir was superior to daily oral tenofovir disoproxil fumarate plus emtricitabine for HIV prevention in two clinical trials. Both trials had the primary aim of establishing the HIV prevention efficacy of long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) compared with tenofovir disoproxil fumarate plus...

Background: Tuberculosis infection (TBI) and tuberculosis disease (TBD) incidence remains poorly described following household contact (HHC) rifampin-/multidrug-resistant tuberculosis exposure. We sought to characterize TBI and TBD incidence at one-year in HHCs and to evaluate tuberculosis preventive therapy (TPT) use in high-risk groups. Methods...

BACKGROUND. Tenofovir-based daily oral HIV pre-exposure prophylaxis (HIV PrEP) is a highly efficacious HIV prevention modality, but sustained use over time isneeded for continued protection among individuals at high risk for HIV exposure. Suboptimal adherence and retention in care threaten to diminish theimpact of HIV PrEP on reducing HIV burden. P...

The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control...

Characterization of HIV risk factors among transwomen and men who have sex with men (MSM) should be assessed separately and independently. However, due to several constraints, these populations continue to be conflated in clinical research and data. There are limited datasets globally powered to make such comparisons. The study aimed to use one of...

The contribution of the HLA-E/NKG2X axis in NK-mediated control of HIV infection remains unclear. We have studied the relationship between HLA-E expression and phenotypical as well as functional characteristics of NK cells, in the context of chronic HIV infection and in an in vitro model of acute infection. High viremia in HIV+ individuals was rela...

Introduction: Characterization of HIV risk factors among transwomen and men who have sex with men (MSM) should be assessed separately and independently. However, due to several constraints, these populations continue to be conflated in clinical research and data. There are limited datasets globally powered to make such comparisons. The study aimed...

The entomopathogenic bacteria Bacillus thuringiensis (Bt) produce parasporal-crystal inclusions composed of different pesticidal proteins such as Cry, that show insecticidal activity against insect pests. Cry toxins are highly susceptible to degradation when exposed to adverse temperature and continuous sun-UV-light. Thus, encapsulation techniques...

Background Primary HIV is characterized by dynamic changes in viral load and innate and adaptive immune responses; it is unclear the extent to which time from acquisition to ART initiation and substance use impact these immunologic changes. Methods We studied plasma immune activation biomarkers, viral load, and CD4 + and CD8 + cell counts in parti...

Bacillus thuringiensis ( Bt ) are soil ubiquitous bacteria. They produce a great variability of insecticidal proteins, where certain of these toxins are used worldwide for pest control. Through their adaptation to diverse ecosystems, certain Bt strains have acquired genetic mobile elements by horizontal transfer, harboring genes that encode for dif...

Introduction Although pre-exposure prophylaxis (PrEP) is a remarkable biomedical advance to prevent HIV, ongoing research on PrEP contributes to and interacts with a legacy of HIV experimentation on marginalized communities in resource-limited settings. This paper explores the complexity of PrEP research mistrust among Peruvian transgender (trans)...

We conducted a pilot randomized controlled trial of a social network-based intervention to promote PrEP adherence among transgender women (TW) in Lima, Peru. We enrolled 89 TW from six social networks and cluster-randomized them 1:1 to standard of care (n = 44) or the TransPrEP intervention (n = 45). Core workshops discussed strategies to support P...

In Lima, Perú, HIV prevalence is estimated to be 15% among men who have sex with men (MSM) and 30% among transgender women (TW). We investigated timely linkage of MSM and TW to HIV care, as linkage to antiretroviral therapy (ART) is critical to protect the health of those living with HIV and to prevent onward transmission. We investigated linkage w...

The identification of new biomarkers is essential to predict responsiveness to vaccines. We investigated the whole-blood transcriptome and microbiome prior to immunization, in order to assess their involvement in induction of humoral responses two months later. We based our analyses on stool and skin microbiota, and blood transcriptome prior to imm...

It is largely unknown how post-translational protein modifications, including glycosylation, impacts recognition of self and non-self T cell epitopes presented by HLA molecules. Data in the literature indicate that O- and N-linked glycosylation can survive epitope processing and influence antigen presentation and T cell recognition. In this perspec...

The insecticidal Cry11Aa and Cyt1Aa proteins are produced by Bacillus thuringiensis as crystal inclusions. They work synergistically inducing high toxicity against mosquito larvae. It was proposed that these crystal inclusions are rapidly solubilized and activated in the gut lumen, followed by pore formation in midgut cells killing the larvae. In a...

Relative control of HIV-1 infection has been linked to genetic and immune host factors. In this study, we analyzed 96 plasma proteome arrays from chronic untreated HIV-1-infected individuals using the classificatory random forest approach to discriminate between uncontrolled disease (plasma viral load [pVL] >50,000 RNA copies/ml; CD4 counts 283 cel...

Background: We assessed sexual behavior and incidence of sexually transmitted infections (STIs) among men who have sex with men and transgender women participating in Sabes, a study of an expanded treatment as prevention strategy focused on early diagnosis and treatment of HIV infection in Lima, Peru (2013-2017). Methods: Sabes participants were...

Background Our previous work has demonstrated the benefits of transcutaneous immunization in targeting Langerhans cells and preferentially inducing CD8 T-cell responses. Methods In this randomized phase Ib clinical trial including 20 HIV uninfected volunteers, we compared the safety and immunogenicity of the MVA recombinant vaccine expressing HIV-...

Background: In Peru, as in the Americas overall, men who have sex with men (MSM) are disproportionately affected by HIV. Most research focuses on practices between cisgender men, while many MSM report male and female partners, cisgender, transgender, or both. Methods: Data for these analyses were from a treatment-as-prevention study in Lima (the...

Spodoptera frugiperda is an important worldwide pest of maize and rice crops that has evolved resistance to Cry1Fa-expressing maize in different countries. Therefore, identification of additional toxins with different modes of action is needed to provide alternative tools to control this insect pest. Bacillus thuringiensis (Bt) Cry1Ab and Cry1Ac to...

Cry proteins produced by Bacillus thuringiensis are pore-forming toxins that disrupt the membrane integrity of insect midgut cells. The structure of such pore is unknown, but it has been shown that domain I is responsible for oligomerization, membrane insertion and pore formation activity. Specifically, it was proposed that some N-terminal α-helice...

GWAS, immune analyses and biomarker screenings have identified host factors associated with in vivo HIV-1 control. However, there is a gap in the knowledge about the mechanisms that regulate the expression of such host factors. Here, we aimed to assess DNA methylation impact on host genome in natural HIV-1 control. To this end, whole DNA methylome...

Background: The identification of new biomarkers is essential to making it possible to predict the degree of protection following vaccination. Very few human studies have focused on baseline characteristics including microbiota and gene expression to underlie vaccine immune responsiveness. We investigated the host whole-blood transcriptome and micr...

Background: In addition to demonstrated public health benefits on reducing transmission, it remains unclear how early antiretroviral therapy (ART) must be started after HIV acquisition to maximize individual benefits. Methods: We conducted an open-label randomized clinical study in Lima, Peru among adult MSM and transgender women with acute (HIV...

Bacillus thuringiensis (Bt) Cyt1Aa toxin shows toxicity to mosquitoes, to certain coleopteran pests and also to red blood cells (RBC). However, its mode of action in the different target cells is not well defined. This protein is a single α-β domain pore-forming toxin, where a β sheet is wrapped by two α-helices layers. The Cyt1Aa α-helix hairpin i...

Accurate HIV risk assessment among men who have sex with men (MSM) is important to help providers assess risk, and target HIV prevention interventions. We sought to develop an evidence-based HIV risk assessment tool for US MSM that is inclusive of Black MSM. Data from four large longitudinal cohorts of MSM were used to develop (EXPLORE), and valida...

Background: Binge drinking (BD) is common in Peru, but may not be routinely detected by standard assessments of hazardous drinking. Objectives: We describe prevalence and risk behaviors of men who have sex with men (MSM) and transgender women (TW) in Peru who met criteria for BD as compared with those who met criteria for hazardous drinking. Method...

Background In Peru, there is an ongoing high-incidence HIV epidemic among men who have sex with men (MSM) and transgender women (TW). Sexual concurrency, or having sex with a partner in between two acts of sex with another partner, may be a key factor in onward HIV transmission. In this study, we quantify concurrency, evaluate factors associated wi...

Background We assessed sexual behavior and sexually transmitted disease risk among men who have sex with men and transgender women participating in Sabes, a study of an expanded treatment as prevention strategy focused on early diagnosis and treatment of HIV infection. Methods Sabes participants were tested monthly for HIV to identify acute or ear...

In Perú, men who have sex with men (MSM) and transgender women (TW) suffer rates of HIV 50 times greater than the general population. MSM or TW sex workers (SWs) are at especially high risk. Daily oral pre-exposure prophylaxis (PrEP) effectively prevents HIV infection if patients adhere to a daily or on-demand regimen. Necessary levels of adoption...

Background: Stigma differentially influences HIV and STI care among MSM, especially regarding partner notification practices. Recognizing the heterogeneous behaviors/identities within the category "MSM," we used mixed-methods to assess sexual risk behaviors among men who have sex with men only (MSMO) and behaviorally bisexual MSM (MSMW) with HIV a...

Objective While men who have sex with men (MSM) are disproportionately affected by Peru’s overlapping HIV and STI epidemics, there are few data on how partnership-level and network-level factors affect STI transmission in Peru. We explored partnership-level and network-level factors associated with gonorrhoea/chlamydia ( Neisseria gonorrhoeae and/o...

Background The Sabes study, a treatment as prevention intervention in Peru, tested the hypothesis that initiating antiretroviral therapy (ART) early in HIV infection when viral load is high, would markedly reduce onward HIV transmission among high-risk men who have sex with men (MSM) and transgender women (TW). We investigated the potential populat...

Background: We assessed multidrug-resistant tuberculosis (MDR-TB) cases and their household contacts (HHCs) to inform the development of an interventional clinical trial. Methods: We conducted a cross-sectional study of adult MDR-TB cases and their HHCs in eight high-TB-burden countries. HHCs underwent symptom screening, chest radiography (CXR),...

Background: Household contacts (HHCs) of individuals with multidrug-resistant tuberculosis (MDR-TB) are at high risk of infection and subsequent disease. There is limited evidence on the willingness of MDR-TB HHCs to take MDR-TB preventive therapy (TPT) to decrease their risk of TB disease. Methods: In this cross-sectional study of HHCs of MDR a...

BACKGROUND Public health strategies are urgently needed to improve HIV disparities among transgender women, including holistic intervention approaches that address those health needs prioritized by the community. Hormone therapy is the primary way many transgender women medically achieve gender identity affirmation. Peer navigation has shown to be...

Background: Public health strategies are urgently needed to improve HIV disparities among transgender women, including holistic intervention approaches that address those health needs prioritized by the community. Hormone therapy is the primary method by which many transgender women medically achieve gender affirmation. Peer navigation has been sh...

Helicoverpa armigera is a polyphagous pest sensitive to Cry1Ac protein from Bacillus thuringiensis (Bt). The susceptibility of the different larval instars of H. armigera to Cry1Ac protoxin showed a significant 45-fold reduction in late instars compared to early instars. A possible hypothesis is that gut surface proteins that bind to Cry1Ac differ...

SDS-PAGE electrophoresis of BBMV isolated from the midgut tissue of different larval instars of H. armigera. The samples were analyzed by SDS-PAGE stained with Coomassie blue. Molecular masses are indicated in kDa. (DOCX)

Purpose: Globally, transgender women (TGW) experience a high burden of adverse health outcomes, including a high prevalence of HIV and sexually transmitted infections (STIs) as well as psychiatric disorders and substance use disorders. To address gaps in HIV research in Peru focused specifically on TGW, this study presents characteristics of a sam...

Bacillus thuringiensis (Bt) Cry toxins are used worldwide for controlling insects. Cry1Ab is produced as a 130 kDa protoxin that is activated by proteolytic removal of an inert 500 amino-acids-long C-terminal region, enabling the activated toxin to bind to insect midgut receptor proteins and leading to its membrane insertion and pore formation. It...

Bacillus thuringiensis Cry1Ca is toxic to different Spodoptera species. The aim of this work was to identify the Cry1Ca binding proteins in S. frugiperda, to provide evidence on their participation in toxicity and to identify the Cry1Ca amino acid residues involved in receptor binding. Pull down assays using S. frugiperda brush border membrane vesi...

Bacillus thuringiensis insecticidal Cry toxins break down larval midgut-cells after forming pores. The 3D-structures of Cry4Ba and Cry5Ba revealed a trimeric-oligomer after cleavage of helices α-1 and α-2a, where helix α-3 is extended and made contacts with adjacent monomers. Molecular dynamic simulations of Cry1Ab-oligomer model based on Cry4Ba-co...

Background: Patient-initiated partner notification (PN) following the diagnosis of a sexually transmitted infection is a critical component of disease control in men who have sex with men (MSM) sexual networks. Both printed and internet-based technologies offer potential tools to enhance traditional partner notification approaches among MSM in res...

In Peru, HIV is concentrated among men who have sex with men (MSM) and transgender women (TGW). Between June 2015 and August 2016, 591 HIV-positive MSM and TGW were recruited at five clinical care sites in Lima, Peru. We found that 82.4% of the participants had achieved viral suppression (VS; VL < 200) and 73.6% had achieved maximal viral suppressi...

The Cyt and Cry toxins are different pore-forming proteins produced by Bacillus thuringiensis bacteria, and used in insect-pests control. Cry-toxins have a complex mechanism involving interaction with several proteins in the insect gut such as aminopeptidase N (APN), alkaline phosphatase (ALP) and cadherin (CAD). It was shown that the loop regions...

The Sabes study evaluates a treatment-as-prevention intervention in cis-gender men who have sex with men and transgender women in Lima, Peru, populations disproportionately affected by the HIV epidemic. The intervention is designed to prevent onward transmission of HIV by identifying HIV-negative, high-risk individuals, testing them monthly for the...

Background: Incidence of HIV infection is still increasing in men who have sex with men (MSM). Undiagnosed HIV-infections are an important factor contributing to this increase and preclude early treatment initiation. Objective: To provide data on incidence HIV infections in high-risk-MSM in an intensified screening program aimed at early diagnos...

Background: Gonorrhea (GC) and chlamydia (CT) disproportionately affect men who have sex with men (MSM), and public health implications vary by anatomic site and bacterial agent. Urethral and rectal GC and CT can increase risk of HIV transmission, while pharyngeal GC may be a reservoir for antimicrobial resistance. To define screening priorities in...

Transgender women (TW) represent a vulnerable population at increased risk for HIV infection in Peru. A mixed-methods study with 48 TW and 19 healthcare professionals was conducted between January and February 2015 to explore barriers and facilitators to implementing a model of care that integrates HIV services with gender-affirmative medical care...

Cell lines have been use extensively for the study of the mode of action of different pore forming toxins produced by different bacterial species. Bacillus thuringiensis Cry toxins are not the exception and their mechanism of action has been analyzed in different cell lines. Here we review the data obtained with different cell lines, including thos...

Objectives A detailed understanding of intentions and practices related to partner notification (PN) following STI diagnosis can improve control strategies. We assessed participant-level and partner-level factors guiding notification behaviour among men who have sex with men and/or with transgender women (MSM-TW) in Lima, Peru, including discordanc...

Bacillus thuringiensis three domain Cry toxins kill insects by forming pores in the apical membrane of larval midgut cells. Oligomerization of the toxin is an important step for pore formation. Domain I helix α-3 participates in toxin oligomerization. Here we identify an intra-molecular salt bridge within helix α-3 of Cry4Ba (D111-K115) that is con...

Condomless anal intercourse among transgender women (TW) in Peru has been shown to vary by the type of partner involved (e.g. primary vs. casual vs. transactional sex partner), but no previous studies have explored variations in partner-level patterns of condom use according to type of anal intercourse. We evaluated the relationship between partner...

In Peru, the HIV epidemic is concentrated in men who have sex with men (MSM) and transgender women (TGW). Multiple studies correlate alcohol use disorders (AUDs) with risky sexual behaviors among Peruvian MSM. Qualitative research was used to inform a clinical trial on the acceptability of medication-assisted therapies to assist management of AUDs...

Introduction Endemic rates of STIs like GC/CT and syphilis in Peru are only partially explained by individual behavioural or biological factors. Characterisation of sexual networks of MSM/TW with syphilis and/or GC/CT can provide critical data to inform prevention efforts. Methods We enrolled 917 MSM/TW as screening for 2 STI control trials in Lim...

Introduction Community acceptability and sustainability of new HIV prevention methods remain key barriers to curb high HIV incidence rates for transgender women (TW) in Peru. Improved understanding of how geography, culture, and socialisation influence HIV-associated risks and uptake of new prevention technologies is critical to address the HIV epi...

Introduction Partner notification (PN) is a key component of STI prevention efforts, yet, is underutilised by MSM, a population at-risk for STIs and HIV in Peru. To understand limiting mechanisms, we examined the dimensionality and latent factor structure of perceived STI and HIV stigma and attitudes towards PN among MSM in Lima, Peru. Methods Bet...

Introduction A detailed understanding of partner notification (PN) practices following STI diagnosis can improve PN strategies. Using data from 2 PN intervention trials in Lima, Peru, we assessed participant- and partner-level factors guiding partner-specific STI notification behaviour, including discordances between anticipated and actual notifica...

Cry1A insecticidal toxins bind sequentially to different larval gut proteins facilitating oligomerization, membrane insertion and pore formation. Cry1Ac interaction with cadherin triggers oligomerization. However, a mutation in an ABC transporter gene (ABCC2) is linked to Cry1Ac resistance in Plutella xylostella. Cry1AcMod, engineered to lack helix...

Background Syphilis in Peru is heavily concentrated in men who have sex with men (MSM) and transgender women (TGW). The aim of the present study was to understand the risk factors for active syphilis infection among MSM and TGW in Peru. Methods: Independent correlates suggestive of active syphilis infection were examined to better understand risk f...

Background: Expedited Partner Therapy (EPT) has been shown to improve treatment outcomes among heterosexual partners of individuals with curable sexually transmitted infections (STIs). Although the use of EPT with men who have sex with men (MSM) has been debated, due to the potential for missed opportunities to diagnose unidentified cases of HIV an...

Neurocognitive impairment (NCI) has been associated with poor clinical outcomes in various patient populations. This study used exploratory factor analysis (EFA) to examine the factor structure of the existing 95-item Neuropsychological Impairment Scale (NIS) to create a suitable NCI screening instrument for people living with HIV (PLH). In Lima, P...

Background: Growth hormone (GH)/insulin-like growth factor (IGF)-1 axis abnormalities have been associated with body composition changes among HIV-infected persons with wasting or lipodystrophy. Little is known of GH/IGF-1 axis alterations with ART initiation or differing ART therapies. Methods: The AIDS Clinical Trials Group Prospective Evaluat...

Introduction: In Peru, transgender women (TW) experience unique vulnerabilities for HIV infection due to factors that limit access to, and quality of, HIV prevention, treatment and care services. Yet, despite recent advances in understanding factors associated with HIV vulnerability among TW globally, limited scholarship has examined how Peruvian T...

Background: Peruvian men who have sex with men (MSM) and transgender women (TGW) experience the double burden of a highly concentrated HIV epidemic with a high prevalence of alcohol use disorders (AUDs). Recent research has associated both with risky sexual behaviors, including unprotected sex, having multiple sexual partners, engaging in sex work...

Objective: Tenofovir has in vitro activity against HSV-2 and reduced HSV-2 acquisition as pre-exposure prophylaxis. Whether tenofovir-containing antiretroviral therapy (ART) reduces HSV-2 acquisition is unknown. Design: Secondary analysis of ACTG A5175, a randomized, open-label study of three ART regimens among 1,571 participants. Methods: HSV...

Immediate antiretroviral therapy (ART) for acute HIV infection (AHI) may decrease HIV transmission in high-risk populations. This study evaluated knowledge of AHI and AHI testing program preferences in Lima, Peru through four semi-structured focus groups with high-risk men who have sex with men (MSM) ( n = 20) and transgender women (TW) ( n = 16)....

Background: Herpes simplex virus type-2 (HSV-2) may heighten immune activation and increase human immunodeficiency virus 1 (HIV-1) replication, resulting in greater infectivity and faster HIV-1 disease progression. An 18-week randomized, placebo-controlled crossover trial of 500 mg valacyclovir twice daily in 20 antiretroviral-naive women coinfect...

Background: We explored the association between alcohol use and condomless receptive (CRAI) and insertive (CIAI) anal intercourse within partnership contexts of men who have sex with men (MSM) and transgender women (TGW) in Lima, Peru. Methods: From 2012-2014, we surveyed men and TGW (n=1607) who reported anal intercourse with ≥1 male or TGW. Al...

Background: New strategies to support partner notification (PN) are critical for STD control and require detailed understanding of how specific individual and partnership characteristics guide notification decisions. Methods: From 2011 to 2012, 397 MSM and TW recently diagnosed with HIV, syphilis, or another STD completed a survey on anticipated...

Quantitative survey instrument. (DOCX)

Qualitative semi-structured interview script. (DOCX)

We investigated whether a 6-amino acid insertion/deletion polymorphism in the mucin domain of TIM-1 (T-cell immunoglobulin and mucin domain 1), modulates susceptibility to HIV-1 infection. The polymorphism was genotyped in three case/control cohorts of HIV-1 exposed seronegative individuals (HESN) and HIV-1 infected subjects from Italy, Peru, and C...

TREND Statement checklist. (DOCX)

HVTN 914: A cohort study in Lima, Peru to evaluate the feasibility of measuring immune responses and activation levels in the foreskin and rectosigmoid mucosa in HIV-negative, uncircumcised men who have sex with men and who are at high risk for HIV acquisition. (PDF)

Results from flow cytometry analysis comparing pre- and post-procedure expression of activation and migration markers in peripheral CD4+ T cells. (DOCX)

Gay, bisexual, and other men who have sex with men (MSM) continue to have disproportionately high burdens of HIV infection in countries of low, middle, and high income in 2016. 4 years after publication of a Lancet Series on MSM and HIV, progress on reducing HIV incidence, expanding sustained access to treatment, and realising human rights gains fo...

Bacillus thuringiensis produces insecticidal proteins that are active against different insect orders. In particular the family of the three domain-Cry toxins (3d-Cry) have important applications in controlling insect pests as spray products or in transgenic Bt-plants. At least three different models account for the mode of action of these proteins...

Insecticidal proteins from Bacillus thuringiensis (Bt) are used extensively in sprays and transgenic crops for pest control, but their efficacy is reduced when pests evolve resistance. Better understanding of the mode of action of Bt toxins and the mechanisms of insect resistance is needed to enhance the durability of these important alternatives t...

Scanning densitometry data for comparing oligomer formation in resistant (AZP-R) and susceptible (APHIS-S) strains of P. gossypiella. (DOCX)

Objectives Men who have sex with men (MSM) are in need of novel and acceptable HIV prevention interventions. In Peru, a Phase II clinical trial was recently completed evaluating rectally applied tenofovir gel among Peruvian MSM and transgender women. If deemed safe and acceptable, the product could move into efficacy testing, but acceptability data...

Background: The genetic bases of natural resistance to HIV-1 infection remain largely unknown. Recently, two genome-wide association studies suggested a role for variants within or in the vicinity of the CYP7B1 gene in modulating HIV susceptibility. CYP7B1 is an appealing candidate for this due to its contribution to antiviral immune responses. We...