International Anal Neoplasia Society's consensus guidelines for anal cancer screening.

The International Anal Neoplasia Society (IANS) developed consensus guidelines to inform anal cancer screening use among various high-risk groups. Anal cancer incidence estimates by age among risk groups provided the basis to identify risk thresholds to recommend screening. Guided by risk thresholds, screening initiation at age 35 years was recommended for men who have sex with men (MSM) and transgender women (TW) with HIV. For other people with HIV and MSM and TW not with HIV, screening initiation at age 45 years was recommended. For solid organ transplant recipients, screening initiation beginning from 10 years post-transplant was recommended. For persons with a history of vulvar precancer or cancer, screening initiation was recommended starting within 1 year of diagnosis of vulvar precancer or cancer. Persons aged ≥45 years with a history of cervical/vaginal HSIL or cancer, perianal warts, persistent (>1 year) cervical HPV16, or autoimmune conditions could be considered for screening with shared decision-making, provided there is adequate capacity to perform diagnostic procedures (high-resolution anoscopy [HRA]). Anal cytology, high-risk (hr) human papillomavirus (HPV) testing (including genotyping for HPV16), and hrHPV-cytology co-testing are different strategies currently used for anal cancer screening that show acceptable performance. Thresholds for referral for HRA or follow-up screening tests are delineated. These recommendations from IANS provide the basis to inform management of abnormal screening results, considering currently available screening tools. These guidelines provide a pivotal foundation to help generate consensus among providers and inform the introduction and implementation of risk-targeted screening for anal cancer prevention.

Exploring the Decision-Making Process of People Living with HIV Enrolled in Antiretroviral Clinical Trials: A Qualitative Study of Decisions Guided by Trust and Emotions.

The informed consent is an ethical and legal requirement for potential participants to enroll in a study. There is ample of evidence that understanding consent information and enrollment is challenging for participants in clinical trials. On the other hand, the reasoning process behind decision-making in HIV clinical trials remains mostly unexplored. This study aims to examine the decision-making process of people living with HIV currently participating in antiretroviral clinical trials and their understanding of informed consent. We conducted a qualitative socio-constructivist study using semi-structured interviews. Eleven participants were selected by purposive sampling in Argentina until data saturation was reached. A content analysis was performed. The findings highlight the fact that some participants decided to enroll on the spot, while others made the decision a few days later. In all cases, the decision was based on different aspects of trust (in doctors, in the clinical research site, in the clinical trials system) but also on emotions associated with HIV and/or treatment. Moreover, while people living with HIV felt truly informed after the consent dialogue with a researcher, consent forms were unintelligible and unfriendly. The immediacy of patient decision-making has rarely been described before. Enrollment in an HIV clinical trial is mainly a trust-based decision but this does not contradict the ethical values of autonomy, voluntariness, non-manipulation, and non-exploitation. Thus, trust is a key issue to be included in reshaping professional practices to ensure the integrity of the informed consent process.

The effect of non-AIDS-defining cancers on people living with HIV.

Non-AIDS-defining cancers are a growing source of morbidity for people with HIV globally. Although people living with HIV have a disproportionately increased risk of developing virally mediated cancers, cancer burden for common non-AIDS-defining cancers that are not virally associated and are linked to ageing, such as prostate cancer, is becoming higher than for virally mediated cancers. Ageing, behavioural, and HIV-specific factors drive the incidence and affect the outcomes of non-AIDS-defining cancers, presenting different challenges for addressing global morbidity and mortality from non-AIDS-defining cancer. Although large population-based studies have shown that people living with HIV with non-AIDS-defining cancers have poorer cancer outcomes than do people without HIV, current guidelines emphasise that people living with HIV with non-AIDS-defining cancers should receive standard, guideline-based treatment, and infectious disease and oncology providers should work closely to address potential drug interactions between antiretroviral therapy and antineoplastic treatment. Most trials target preventive measures focusing on non-AIDS-defining cancers. However, treatment trials for the optimal management of people living with HIV and non-AIDS-defining cancer, including interventions such as immunotherapies, are needed to improve non-AIDS-defining cancer outcomes.

The HIV care cascade in Buenos Aires, Argentina: results in a tertiary referral hospital.

OBJECTIVE: To determine rates of retention, antiretroviral therapy (ART) use, and viral suppression in an adult cohort from a public tertiary referral hospital in the city of Buenos Aires, Argentina. METHODS: HIV-positive ART-naïve patients ≥ 18 years old starting care 2011-2013 contributed data until the end of 2014. Three outcomes were assessed in 2014: retention in care, ART use, and viral suppression. Patient characteristics associated with each outcome were assessed through logistic regression. RESULTS: A total of 1 031 patients were included. By the end of 2014, 1.5% had died and 14.8% were transferred to a different center. Of the remaining 859 patients, 563 (65.5%) were retained in 2014. Among those retained, 459 (81.5%) were on ART in 2014. Of those 459 on ART, 270 (58.8%) were virologically suppressed. Younger age was associated with lower retention (OR (odds ratio): 0.67; 95% CI (confidence interval): 0.44-0.92 for ≥ 35 vs. < 35 years), but unrelated with ART use or viral suppression. Low CD4 count at first visit was associated with ART use (OR: 35.72 for CD4 < 200, 7.13 for CD4 200-499 vs. ≥ 500, P < 0.001) and with virologic suppression (OR: 2.17 for CD4 < 200, 2.46 for CD4 200-499 vs. ≥ 500, P: 0.023). CONCLUSIONS: Our hospital in Buenos Aires is still below the recommended 90-90-90 targets of the Joint United Nations Programme on HIV/AIDS (UNAIDS) for ART use and viral suppression. We found a major gap in retention in care. Identifying younger age as being associated with worse retention will help in the design of targeted interventions.

Temporal Trends in Age at HIV Diagnosis in Cohorts in the United States, the Caribbean, and Central and South America.

In the United States (USA), the age of those newly diagnosed with HIV is changing, particularly among men who have sex with men (MSM). A retrospective analysis included HIV-infected adults from seven sites in the Caribbean, Central and South America network (CCASAnet) and the Vanderbilt Comprehensive Care Clinic (VCCC-Nashville, Tennessee, USA). We estimated the proportion of patients <25 years at HIV diagnosis by calendar year among the general population and MSM. 19,466 (CCASAnet) and 3,746 (VCCC) patients were included. The proportion <25 years at diagnosis in VCCC increased over time for both the general population and MSM (p < 0.001). Only in the Chilean site for the general population and the Brazilian site for MSM were similar trends seen. Subjects <25 years of age at diagnosis were less likely to be immunocompromised at enrollment at both the VCCC and CCASAnet. Recent trends in the USA of greater numbers of newly diagnosed young patients were not consistently observed in Latin America and the Caribbean. Prevention efforts tailored to young adults should be increased.

Treatment as prevention: are Argentinean HIV care providers willing to adopt earlier antiretroviral therapy?

HIV guidelines increasingly recommend antiretroviral therapy (ART) initiation at a higher CD4 levels. The extent to which these evolving standards are translated into routine clinical care has not been evaluated in Argentina. During October 2012, we conducted an online survey among Argentinean HIV clinicians to assess their attitudes and practices toward ART initiation and its potential use for HIV prevention. Of the 280 physicians included, 61% would prescribe ART at CD4 ≤ 500 cells/µL for asymptomatic patients. Although, only 11% would recommend ART irrespective of CD4 cell count, 72% would do it for serodiscordant couples, and 75% for sex workers. Most participants agreed that they would consider earlier initiation of ART if transmission risk exists, and that expansion of ART could help decrease HIV incidence. These results suggest that a large proportion of Argentinean HIV care providers are willing to adopt the recently updated Argentinean guidelines recommending earlier ART, especially when high HIV transmission risk exists.

Cancer in People with HIV.

We review the intersection of human immunodeficiency virus (HIV) and cancer globally, including the complex interplay of oncogenic infections, chronic inflammation, and behavioral and other factors in increasing cancer risk among people with HIV (PWH). We discuss current cancer screening, prevention, and treatment recommendations for PWH. Specific interventions include vaccination, behavioral risk reduction, timely HIV diagnosis and treatment, screening for specific cancer sites, and multifaceted treatment considerations unique to PWH including supportive care and drug interactions. Finally, the potential of novel therapies and the need for inclusive cancer clinical trials are highlighted. Collaborative multidisciplinary efforts are critical for continued progress against cancer among PWH.

Transcriptome and microbiome-immune changes across preinvasive and invasive anal cancer lesions.

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy linked to high-risk Human papillomavirus (HPV) infection, which develops from precursor lesions like Low-Grade Squamous Intraepithelial Lesions (LGSIL) and High-Grade Squamous Intraepithelial Lesions (HGSIL). ASCC incidence varies across populations, posing increased risk for People Living with HIV (PLWH). Our investigation focused on transcriptomic and metatranscriptomic changes from Squamous Intraepithelial Lesions (SILs) to ASCC. Metatranscriptomic analysis highlighted specific bacterial species (e.g., Fusobacterium nucleatum, Bacteroides fragilis) more prevalent in ASCC than precancerous lesions. These species correlated with gene encoding enzymes (Acca, glyQ, eno, pgk, por) and oncoproteins (FadA, dnaK), presenting potential diagnostic or treatment markers. Unsupervised transcriptome analysis identified distinct sample clusters reflecting histological diagnosis, immune infiltrate, HIV/HPV status, and pathway activities, recapitulating anal cancer progression's natural history. Our study unveiled molecular mechanisms in anal cancer progression, aiding in stratifying HGSIL cases based on low- or high-risk progression to malignancy.

Benznidazole treatment of chagasic encephalitis in pregnant woman with AIDS.

We report a case of chagasic meningoencephalitis reactivation in a pregnant woman co-infected with Trypanosoma cruzi and HIV that was successfully managed with benznidazole and highly active antiretroviral therapy. Early diagnosis enabled rapid specific treatment that improved the health of the patient and her baby.

Retention among transgender women treated with dolutegravir associated with tenofovir/lamivudine or emtricitabine in Argentina: TransViiV study.

In Argentina, transgender women (TGW) have a high HIV prevalence (34%). However, this population shows lower levels of adherence, retention in HIV care and viral suppression than cisgender patients. The World Health Organization (WHO) recommends the transition to dolutegravir (DTG)-based regimens to reduce adverse events and improve adherence and retention. The purpose of this study was to determine retention, adherence and viral suppression in naïve TGW starting a DTG-based first-line antiretroviral treatment (ART) and to identify clinical and psychosocial factors associated with retention. We designed a prospective, open-label, single-arm trial among ART-naïve HIV positive TGW (Clinical Trial Number: NCT03033836). Participants were followed at weeks 4, 8, 12, 24, 36 and 48, in a trans-affirmative HIV care service that included peer navigators, between December, 2015 and May, 2019. Retention was defined as the proportion of TGW retained at week 48 and adherence was self-reported. Viral suppression at <50 copies/mL was evaluated using snapshot algorithm and as per protocol analysis. Of 75 TGW screened, 61 were enrolled. At baseline, median age was 28 y/o., HIV-1-RNA (pVL) 46,908 copies/mL and CD4+ T-cell count 383 cells/mm3. At week 48, 77% were retained and 72% had viral suppression (97% per protocol). The regimen was well tolerated and participants reported high adherence (about 95%). Eleven of the fourteen TGW who discontinued or were lost to follow-up had undetectable pVL at their last visit. Older age was associated with better retention. DTG-based treatment delivered by a trans-competent team in a trans-affirmative service was safe and well tolerated by TGW and associated with high retention, high adherence and high viral suppression at 48 weeks among those being retained.

Latin American and the Caribbean Code Against Cancer 1st edition: Infections and cancer.

About 13% of all cancers around the world are associated with infectious agents, particularly in low-resource settings. The main infectious agents associated with cancer are Helicobacter pylori (H. pylori), that causes gastric cancer, human papillomavirus (HPV) that causes cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancer, hepatitis B and C viruses that cause liver cancer, and human immunodeficiency virus (HIV), associated with cancers of the cervix, Kaposi sarcoma (KS) and non-Hodgkin´s lymphoma. In Latin America and the Caribbean (LAC), about 150,000 cancer cases are caused annually by infections. The LAC Cancer Code Against Cancer consists of a set of 17 evidence-based and individual-level cancer prevention recommendations targeted to the general population, suited to the epidemiological, socioeconomic, and cultural conditions of the region, and tailored to the availability and accessibility of health-care systems. The recommendations with respect to infection-driven malignancies include testing and treating for H. pylori in the context of specific public health programs, vaccination against HPV and Hepatitis B Virus (HBV) and detection and treatment of chronic infections with HBV, Hepatitis C virus (HCV) and HIV, in addition to the promotion of safe sex and use of condoms to prevent sexually transmitted infections (STI). Countries, policy makers, health care systems and individuals should consider the adoption of these recommendations to help reduce the incidence and mortality of infection-related cancers in LAC, to improve quality of life of individuals and reduce the costs of cancer care in the region.

Oral and anal microbiome from HIV-exposed individuals: role of host-associated factors in taxa composition and metabolic pathways.

Evidence indicates that the microbiome plays a significant role in HIV immunopathogenesis and associated complications. This study aimed to characterize the oral and anal microbiome of Men who have Sex with Men (MSM) and Transgender Women (TGW), with and without HIV. One hundred and thirty oral and anal DNA-derived samples were obtained from 78 participants and subjected to shotgun metagenomics sequencing for further microbiome analysis. Significant differences in the microbiome composition were found among subjects associated with HIV infection, gender, sex behavior, CD4+ T-cell counts, antiretroviral therapy (ART), and the presence of HPV-associated precancerous anal lesions. Results confirm the occurrence of oncogenic viromes in this high HIV-risk population. The oral microbiome in HIV-associated cases exhibited an enrichment of bacteria associated with periodontal disease pathogenesis. Conversely, anal bacteria showed a significant decrease in HIV-infected subjects (Coprococcus comes, Finegoldia magna, Blautia obeum, Catenibacterium mitsuokai). TGW showed enrichment in species related to sexual transmission, which concurs that most recruited TGW are or have been sex workers. Prevotella bivia and Fusobacterium gonidiaformans were positively associated with anal precancerous lesions among HIV-infected subjects. The enrichment of Holdemanella biformis and C. comes was associated with detectable viral load and ART-untreated patients. Metabolic pathways were distinctly affected by predominant factors linked to sexual behavior or HIV pathogenesis. Gene family analysis identified bacterial gene signatures as potential prognostic and predictive biomarkers for HIV/AIDS-associated malignancies. Conclusions: Identified microbial features at accessible sites are potential biomarkers for predicting precancerous anal lesions and therapeutic targets for HIV immunopathogenesis.

Redesigning an Electronic Health Record in Argentina to Improve Comprehensive Health Care and Clinical Research.

Updating electronic health record systems to meet new clinic needs and government regulations presents an ongoing challenge for health care organizations. To redesign an existing system for two HIV clinics in Argentina, we employed a three-phase approach of exploration, participatory design, and prototyping. The process and resulting architecture of the HIV-centered "RedClin" electronic health record may inform electronic health records at other clinics in Latin America and worldwide.

Design and Development of an Electronic Health Record According to Argentine Gender Identity Law.

Health information systems face the challenge of collecting data on patients' gender identity. The absence of this information may lead the patients to situations of vulnerability and discrimination. The objective of this study is to describe the process of designing and developing an Electronic Health Record according to the Argentine Gender Identity Law. This health record allows clinics to record legal names and surnames, other social names, gender identity, sex at birth, and legal sex.

Decision-making in HIV clinical trials: a study with patients enrolled in antiretroviral trials.

OBJECTIVE: To explore the decisional process of people living with human immunodeficiency virus (HIV) currently enrolled in antiretroviral clinical trials. METHOD: Cross-sectional retrospective study. Outcome variables were reasons to participate, perceived decisional role (Control Preference Scale), the Decisional Conflict Scale and the Decisional Regret Scale. Descriptive statistics were calculated, and associations among these variables and with sociodemographic and clinical characteristics were analyzed with non-parametric techniques. RESULTS: Main reasons to participate were gratitude towards Fundación Huesped (47%), the doctor's recommendation (32%), and perceived difficulty to access treatment in a public hospital (28%). Most patients thought that they made their decision alone (54.8%) or collaboratively with the physician (43%). Decisional conflict was low, with only some conflict in the support subscale (median=16.67). Education was the only significant correlate of the total decisional conflict score (higher in less educated patients; p=0.018), whereas education, recent diagnosis, living alone, lower age, being man and doctor's recommendation to go to Fundación Huésped related to higher conflict in different subscales. Nobody regretted to participate. CONCLUSIONS: The decision making regarding participation in HIV trials, from the perspective of participants, was made respecting their autonomy and with very low decisional conflict. Currently, patients show no signs of regret. However, even in this favorable context, results highlight the necessity of enhancing the decision support in more vulnerable patients (e.g., less educated, recently diagnosed or with less social support), thus warranting equity in the quality of the decision making process.

Antiretroviral therapy and Kaposi's sarcoma trends and outcomes among adults with HIV in Latin America.

INTRODUCTION: Kaposi's sarcoma (KS) remains the most frequent malignancy in persons living with HIV (PWH) in Latin America. We examined KS trends and outcomes from Latin American clinical sites in the era of increased access to antiretroviral therapy (ART). METHODS: Cohorts in Brazil, Peru, Mexico, Honduras, Argentina and Chile contributed clinical data of PWH ≥16 years old from 2000 to 2017, excluding patients with KS diagnosed before clinic enrolment. We compared KS incidence over time using multivariable incidence rate ratios. Predictors of KS before/at or after ART initiation and of mortality after KS were examined using Cox regression. RESULTS: Of 25 981 PWH, 481 had incident KS, including 200 ART-naïve and 281 ART-treated patients. From 2000 to 2017, the incidence of KS decreased from 55.1 to 3.0 per 1000 person-years. In models adjusting for CD4 and other factors, the relative risk for KS decreased from 2000 to 2008. Since 2010, the adjusted risk of KS increased in the periods before and ≤90 days after ART initiation but decreased >90 days after ART. In addition to low CD4 and male-to-male sex, KS risk after ART was associated with age and history of other AIDS-defining illnesses. Mortality after KS (approximately 25% after five years) was not associated with either year of KS diagnosis nor timing of diagnosis relative to ART initiation. CONCLUSIONS: KS incidence in Latin America has remained stable in recent years and risk is highest before and shortly after ART initiation. Early diagnosis of HIV and ART initiation remain critical priorities in the region.

Association between HIV-1 RNA level and CD4 cell count among untreated HIV-infected individuals.

OBJECTIVES: We examined the significance of plasma HIV-1 RNA levels (or viral load alone) in predicting CD4 cell decline in untreated HIV-infected individuals. METHODS: Data were obtained from the British Columbia Centre for Excellence in HIV/AIDS. Participants included all residents who ever had a viral load determination in the province and who had never taken antiretroviral drugs (N = 890). We analyzed a total of 2074 viral load measurements and 2332 CD4 cell counts. Linear mixed-effects models were used to predict CD4 cell decline over time. RESULTS: Longitudinal viral load was strongly associated with CD4 cell decline over time; an average of 1 log(10) increase in viral load was associated with a 55-cell/mm(3) decrease in CD4 cell count. CONCLUSIONS: Our results support the combined use of CD4 cell count and viral load as prognostic markers in HIV-infected individuals before the introduction of antiretroviral therapy.

Impact of HIV-ART on the restoration of Th17 and Treg cells in blood and female genital mucosa.

The aim of this study was to evaluate the effectiveness of antiretroviral treatment (ART) on the proportion and functions of Th17 and Treg cells in peripheral blood and female genital tract (FGT) respectively. To this aim, samples from 41 HIV-neg, 33 HIV+ ART-naïve and 32 HIV+ ART+ subjects were obtained. In peripheral blood, altered Th17 and Th17/Treg proportions were normalized in HIV+ ART+, but certain abnormal Treg and activated T-cell proportions were still observed. In FGT, abnormal patterns of secretion for Th17-related cytokines were observed in cervical mononuclear cells (CMCs) from HIV+ women, even in those from HIV+ ART+, compared to the HIV-neg group. Moreover, these altered patterns of secretion were associated with diminished levels of CXCL5 and CXCL1 chemokines and with an immunoregulatory skew in the CCL17/CCL20 ratio in ectocervix samples of these women. Finally, ART did not restore proportions of Th17-precursor cells with gut-homing potential in PBMCs, and positive correlations between these cells and the levels of IL-17F and IL-21 production by CMCs may suggest that a better homing of these cells to the intestine could also imply a better restoration of these cells in the female genital tract. These results indicate that antiretroviral treatment did not restore Th17-related immune functions completely at the female mucosal level.

Fostemsavir: a new CD4 attachment inhibitor.

PURPOSE OF REVIEW: Even in the era of modern HAART, antiretroviral (ARV) failure and emergence of drug resistance is still a problem worldwide. New classes with different mechanisms of action are needed to overcome this challenge. After the integrase inhibitors were launched, more than a decade ago, no new classes were added to the ARV armamentarium. RECENT FINDINGS: Fostemsavir (FTR) is an attachment inhibitor, active regardless of viral tropism, without cross-resistance to any of the existing ARV compounds. A phase 3 study showed a reduction in plasma viral RNA of 1.21-1.73 log10 copies/ml from baseline after 8 days of functional monotherapy; at 48 weeks, up to 82% of patients treated with FTR and an optimized background ARV regimen achieved virological suppression below 50 copies/ml. SUMMARY: FTR is an investigational HIV drug with a novel mechanism of action that demonstrates virologic activity in HIV-infected treatment-experienced individuals.