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.

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.

Biterapia con atazanavir/ritonavir más raltegravir versus terapia triple en segunda línea: Ensayo ARTE / ATV/r+RAL (DT) after failure with NNRTI

Antecedentes: La terapia dual ha surgido como un nuevo concepto para el tratamiento del VIH. Este estudio tenía como objetivo comparar un régimen dual basado en ATV/r + RAL (TD) frente a estándar de tres drogas con ATV/r + TDF/FTC (TT) luego del fracaso de un primer esquema ba-sado en INNTR.ClinicalTrials.gov, Número: NCT01829802.Método: Estudio piloto abierto, multicéntrico y aleatoriza-do. Resultado primario: proporción de sujetos con ARN del VIH-1 menor a 50 copias/mL en semana 48 (S48). Resulta-dos secundarios: discontinuaciones asociadas a eventos adversos (EA), tiempo transcurrido hasta la supresión viral, desarrollo de mutaciones de resistencia a la integrasa y proteasa, cambio en recuento de CD4. Resultados: De los 57 participantes seleccionados, 34 fue-ron asignados aleatoriamente para recibir: TD (n: 18) o TT (n: 16). En semana 48, 67% (n: 12/18) en TD tuvo respues-ta virológica y 88% (n: 14/16) en rama según el análisis FDA, intención de tratamiento/expuestos (p = NS) y 73% (TD) y 93% (TT) según análisis por protocolo (p = NS). El cambio de CD4 entre basal - S48: +119 y +52 células/µL en DT y TT, respectivamente. Cuatro participantes en TD y uno en TT presentaron fracaso virológico en la semana 48. Un participante desarrolló una mutación de resistencia a integrasa (155H).Conclusión: ATV/r+RAL como terapia dual de segunda línea mostró una tendencia al fracaso virológico más frecuente, en comparación con TT, aunque el estudio piloto no tenía potencia para demostrar esta diferencia. Este estudio está registrado en ClinicalTrials.gov, Número: NCT01829802

Background: Dual therapy has emerged as a novel concept for HIV treatment. This study was aimed at comparing a nucleoside-sparing dual regimen consisting of ATV/r + RAL (DT) vs standard therapy of ATV/r + TDF/FTC (TT) among individuals failing first NNRTI-containing treatment.Methods: Randomized multicenter open-label pilot study. Primary outcome: proportion of subjects with plasma HIV-1 RNA below the limit of detection (<50 copies/mL) at 48 weeks (W48). Secondary outcomes: proportion of discontinuation due to adverse events (AEs), time until viral suppression, time until loss of virological response, development of integrase resistance mutations, and absolute change in CD4 counts. The primary outcome was analyzed using the FDA snapshot analysis.Results: Out of 57 participants screened, 34 were randomized to receive: DT (n: 18) or TT (n: 16). At W48, virological response was achieved in 67% (n: 12/18) of participants receiving DT and 88% (n: 14/16) receiving TT by FDA snapshot analysis (p = NS) and 73% and 93% by per-protocol analysis (p = NS). CD4 cell count median change from baseline to W48 was +119 and + 52 cell/µL in DT and TT, respectively. Four participants receiving DT and one TT presented virological failure at W48, with low pVL. One participant developed an integrase resistance mutation (155H) and suppressed later on TT.Conclusion: ATV/r+RAL as second-line therapy showed a trend to more frequent virological failure, compared to TT, although the study was unpowered to prove this difference. No major differences were seen in tolerance or toxicity.This study is registered with ClinicalTrials.gov, Number: NCT01829802

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.

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.

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.

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.

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.

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.

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.

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.

Infección por HPV de alto riesgo y lesiones intraepiteliales anales en hombres HIV positivos que tienen sexo con hombres / High Risk GPV infection and anal Intraepithelial lesions in HIV positive men who have sex whit men

Introducción: El cáncer anal, asociado a la infección con virus de papiloma humano de alto riesgo (HPV-AR), es muy frecuente en hombres que tienen sexo con hombres (HSH) HIV+. Objetivo: Evaluar frecuencia de infección por HPV-AR, genotipos y lesiones asociadas, y factores asociados.Materiales y métodos: Estudio en HSH HIV+ (septiembre 2012-marzo 2014, Hospital Fernández). Se recogió información demográfica, de HIV, HPV y prácticas sexuales. Se realizó citología anal, detección de HPV-AR (HC2 High-Risk HPV DNA, Digene®) y genotipificación en las muestras HPV-AR+ (Inno Lipa®, Fujirebio). Los pacientes firmaron consentimiento informado. Se indicó tratamiento según resultados. Resultados: Completaron el estudio 57 pacientes. Mediana de edad: 40 años (rango intercuartil [RIC]: 29-45); de CD4: 444 cels/mm3 (RIC: 345-568); 77% recibían tratamiento antirretroviral, 68% con carga viral no detectable. Citologías: negativas (24%); lesión intraepitelial de bajo grado (54%); lesión intraepitelial de alto grado (20%); ASCUS (2%). El 80% fue HPV-AR+. Los pacientes con diagnóstico de HPV-AR (p=0,006) y de lesión intraepitelial tuvieron CD4 <500 cels/mm3 con más frecuencia (p=0,030). Los pacientes con HPV-AR tuvieron mayor frecuencia de carga viral detectable (p=0,020, prueba de Fisher). El porcentaje de pacientes con uso consistente de preservativo fue mayor entre los pacientes sin lesión citológica (p=0,026). Genotipos de alto riesgo más frecuentes: HPV-16 (51%), HPV-31 (44%) y HPV-51 (40%); de bajo riesgo: HPV-6 (47%) y HPV-44 (35%).Conclusiones: Se encontró elevada frecuencia de lesión citológica (76%) y de HPV-AR (80%). Es necesario establecer estrategias de prevención en esta población incluyendo tamizaje, vacunación y promoción de sexo seguro.Palabras clave: HIV, lesión intraepitelial anal, HPV, citología anal, tamizaje de cáncer anal, hombres que tienen sexo con hombre

ntroduction: Anal cancer, associated with the infection with high risk Human Papillomavirus (HR-HPV), is very frequent among HIV+ men who have sex with men (MSM). Objective: To evaluate the frequency of HR-HPV infection, presence of HPV genotypes and HPV- associated lesions and associated factors.Methods: Study in HIV+ MSM (September 2012- March 2014, Hospital Fernández). Demographical, HIV, HPV and sexual behaviour information was collected. Cytology, HR-HPV detection (HC2 High-Risk HPV DNA, Digene ®) and genotyping was performed on samples positive for HR-HPV (Inno Lipa®, Fujirebio). All patients signed informed consent. Treatment was provided according to results.Results: Fifty-seven patients completed the study. Median age was 40 years old (interquartile range [IQR]: 29-45); median CD4 cell count: 444 cels/mm3 (IQR: 345-568); 77% were under ARV treatment, 68% with undetectable viral load. Cytology results: 24% negative, 54% low grade intraepithelial lesion, 20% high grade intraepithelial lesion, 2% ASCUS. Eighty percent were HR-HPV+. Patients with HR-HPV (p=0,006) and diagnosis of intraepithelial lesion had more frequent CD4 <500 cels/mm3 (p=0,030). Patients diagnosed with HR-HPV had a higher frequency of detectable viral load (p=0,020, prueba de Fisher). The percentage of patients with consistent condom use was higher among patients without cytological lesion (p=0,026).Most frequent high risk genotypes: HPV-16 (51%), HPV-31 (44%) and HPV-51 (40%); low risk genotypes HPV-6 (47%) and HPV-44 (35%).Conclusions: There was high frequency of cytological lesions (76%) and HR-HPV (80%). It is necessary to promote prevention strategies in this population including screening, vaccine and safe sex promotion

Survival after cancer diagnosis in a cohort of HIV-positive individuals in Latin America.

BACKGROUND: This study aimed to evaluate trends and predictors of survival after cancer diagnosis in persons living with HIV in the Caribbean, Central, and South America network for HIV epidemiology cohort. METHODS: Demographic, cancer, and HIV-related data from HIV-positive adults diagnosed with cancer ≤ 1 year before or any time after HIV diagnosis from January 1, 2000-June 30, 2015 were retrospectively collected. Cancer cases were classified as AIDS-defining cancers (ADC) and non-AIDS-defining cancers (NADC). The association of mortality with cancer- and HIV-related factors was assessed using Kaplan-Meier curves and Cox proportional hazards models stratified by clinic site and cancer type. RESULTS: Among 15,869 patients, 783 had an eligible cancer diagnosis; 82% were male and median age at cancer diagnosis was 39 years (interquartile range [IQR]: 32-47). Patients were from Brazil (36.5%), Argentina (19.9%), Chile (19.7%), Mexico (19.3%), and Honduras (4.6%). A total of 564 ADC and 219 NADC were diagnosed. Patients with NADC had similar survival probabilities as those with ADC at one year (81% vs. 79%) but lower survival at five years (60% vs. 69%). In the adjusted analysis, risk of mortality increased with detectable viral load (adjusted hazard ratio [aHR] = 1.63, p = 0.02), age (aHR = 1.02 per year, p = 0.002) and time between HIV and cancer diagnoses (aHR = 1.03 per year, p = 0.01). CONCLUSION: ADC remain the most frequent cancers in the region. Overall mortality was related to detectable viral load and age. Longer-term survival was lower after diagnosis of NADC than for ADC, which may be due to factors unrelated to HIV.

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.

The HIV care cascade in Buenos Aires, Argentina: results in a tertiary referral hospital / La cascada en la atención de la infección por el VIH en Buenos Aires, Argentina: resultados en un hospital de referencia de atención terciaria

ABSTRACT 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.

RESUMEN Objetivo Determinar las tasas de retención, uso de tratamiento antirretroviral (TAR) y supresión viral en una cohorte adulta de un hospital público de referencia de atención terciaria en la ciudad de Buenos Aires (Argentina). Métodos Pacientes de 18 años de edad o mayores seropositivos al VIH que no habían recibido tratamiento con antirretrovirales y que comenzaron a ser atendidos entre el 2011 y el 2013 aportaron datos hasta finales del 2014. En el 2014 se evaluaron tres resultados: la retención de los pacientes en los servicios de atención, el uso de TAR y la supresión viral. Se usó la regresión logística para evaluar las características de los pacientes asociadas con cada resultado. Resultados Se estudió a 1 031 pacientes. A finales del 2014, 1,5% habían fallecido y 14,8% fueron transferidos a otro centro. De los 859 pacientes restantes, en el 2014 se retuvieron en los servicios a 563 (65,5%). Entre los que siguieron asistiendo a los servicios, 459 (81,5%) recibieron tratamiento antirretroviral ese año. De esos 459 que recibieron tratamiento antirretroviral, se alcanzó la supresión viral en 270 (58,8%). Se determinó que una menor edad estaba asociada a una menor tasa de retención (razón de posibilidades (OR): 0,67; intervalo de confianza de 95% (IC): 0,44-0,92 para ≥ 35 frente a < 35 años), pero no con el uso de tratamiento antirretroviral o la supresión viral. También se determinó que un bajo nivel de CD4 en la primera consulta estaba asociado al uso de tratamiento antirretroviral (OR: 35,72 para CD4 < 200, 7,13 para CD4 200-499 frente a ≥ 500, P < 0,001) y a la supresión viral (OR: 2,17 para CD4 < 200, 2,46 para CD4 200-499 frente a ≥ 500, P: 0,023). Conclusiones Nuestro hospital en Buenos Aires todavía está por debajo de las metas 90‑90‑90 recomendadas por el Programa Conjunto de las Naciones Unidas sobre el VIH/SIDA (ONUSIDA) para el uso de terapia antirretroviral y la supresión viral. Encontramos una brecha importante en la retención de los pacientes en los servicios de atención. La asociación de una menor edad con peores tasas de retención será útil en el diseño de intervenciones destinadas a poblaciones específicas.

Time to HAART Initiation after Diagnosis and Treatment of Opportunistic Infections in Patients with AIDS in Latin America.

BACKGROUND: Since 2009, earlier initiation of highly active antiretroviral therapy (HAART) after an opportunistic infection (OI) has been recommended based on lower risks of death and AIDS-related progression found in clinical trials. Delay in HAART initiation after OIs may be an important barrier for successful outcomes in patients with advanced disease. Timing of HAART initiation after an OI in "real life" settings in Latin America has not been evaluated. METHODS: Patients in the Caribbean, Central and South America network for HIV Epidemiology (CCASAnet) ≥18 years of age at enrolment, from 2001-2012 who had an OI before HAART initiation were included. Patients were divided in an early HAART (EH) group (those initiating within 4 weeks of an OI) and a delayed HAART (DH) group (those initiating more than 4 weeks after an OI). All patients with an AIDS-defining OI were included. In patients with more than one OI the first event reported was considered. Calendar trends in the proportion of patients in the EH group (before and after 2009) were estimated by site and for the whole cohort. Factors associated with EH were estimated using multivariable logistic regression models. RESULTS: A total of 1457 patients had an OI before HAART initiation and were included in the analysis: 213 from Argentina, 686 from Brazil, 283 from Chile, 119 from Honduras and 156 from Mexico. Most prevalent OI were Tuberculosis (31%), followed by Pneumocystis pneumonia (24%), Invasive Candidiasis (16%) and Toxoplasmosis (9%). Median time from OI to HAART initiation decreased significantly from 5.7 (interquartile range [IQR] 2.8-12.1) weeks before 2009 to 4.3 (IQR 2.0-7.1) after 2009 (p<0.01). Factors associated with starting HAART within 4 weeks of OI diagnosis were lower CD4 count at enrolment (p-<0.001), having a non-tuberculosis OI (p<0.001), study site (p<0.001), and more recent years of OI diagnosis (p<0.001). DISCUSSION: The time from diagnosis of an OI to HAART initiation has decreased in Latin America coinciding with the publication of evidence of its benefit. We found important heterogeneity between sites which may reflect differences in clinical practices, local guidelines, and access to HAART. The impact of the timing of HAART initiation after OI on patient survival in this "real life" context needs further evaluation.

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.

Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study.

BACKGROUND: Access to combination antiretroviral therapy (ART) is expanding in Latin America (Mexico, Central America, and South America) and the Caribbean. We assessed the incidence of and factors associated with regimen failure and regimen change of initial ART in this region. METHODS: This observational cohort study included antiretroviral-naive adults starting ART from 2000 to 2014 at sites in seven countries throughout Latin America and the Caribbean. Primary outcomes were time from ART initiation until virological failure, major regimen modification, and a composite endpoint of the first of virological failure or major regimen modification. Cumulative incidence of the primary outcomes was estimated with death considered a competing event. FINDINGS: 14,027 patients starting ART were followed up for a median of 3.9 years (2.0-6.5): 8374 (60%) men, median age 37 years (IQR 30-44), median CD4 count 156 cells per µL (61-253), median plasma HIV RNA 5.0 log10 copies per mL (4.4-5.4), and 3567 (28%) had clinical AIDS. 1719 (12%) patients had virological failure and 1955 (14%) had a major regimen change. Excluding the site in Haiti, which did not regularly measure HIV RNA, cumulative incidence of virological failure was 7.8% (95% CI 7.2-8.5) 1 year after ART initiation, 19.2% (18.2-20.2) at 3 years, and 25.8% (24.6-27.0) at 5 years; cumulative incidence of major regimen change was 5.9% (5.3-6.4) at 1 year, 12.7% (11.9-13.5) at 3 years, and 18.2% (17.2-19.2) at 5 years. Incidence of major regimen change at the site in Haiti was 10.7% (95% CI 9.7-11.6) at 5 years. Virological failure was associated with younger age (adjusted hazard ratio [HR] 2.03, 95% CI 1.68-2.44, for 20 years vs 40 years), infection through injection drug use (vs infection through heterosexual sex; 1.60, 1.02-2.52), and initiation in earlier calendar years (1.28, 1.13-1.46, for 2002 vs 2006), but was not significantly associated with boosted protease inhibitor-based regimens (vs non-nucleoside reverse transcriptase inhibitor; 1.17, 1.00-1.36). INTERPRETATION: Incidence of virological failure in Latin America and the Caribbean was generally lower than that reported in North America or Europe. Our results suggest the need to design strategies to reduce failure and major regimen change in young patients and those with a history of injection drug use. FUNDING: US National Institutes of Health.