Implementation of a rapid diagnostic assay package for cryptococcosis, histoplasmosis and tuberculosis in people living with HIV in Paraguay.

BACKGROUND: Opportunistic infections (OIs) are common causes of mortality among people living with HIV (PLHIV). We determined prevalence and 30-day mortality due to histoplasmosis, cryptococcosis, and TB in PLHIV with advanced HIV disease (AHD). METHODS: PLHIV 18 years and older, with a CD4 + T-cell count of less than 350 cells/mm3 newly diagnosed with HIV infection or re-engaged in care after being without ART for more than 90 days (Group A). The second group included symptomatic PLHIV regardless of ART status or CD4 + T-cell count (Group B); all followed for 30 days. Detection of Histoplasma Ag (HisAg) in urine was done by enzyme immunoassay (EIA), Cryptococcus antigen (CrAg) was detected in serum and cerebrospinal fluid (CSF) specimens by lateral flow assay (LFA), and lipoarabinomannan (LAM) detection in urine was by LFA (TB LAM) and in sputum by GeneXpert for diagnosis of Mycobacterium infections. RESULTS: From August 2021 to June 2022, 491 PLHIV were enrolled; 482 (98%) had a CD4 + T-cell result, and 381 patients (79%) were classified with AHD according to CD4 + T-cell count (< 200 CD4/mm3). Frequency of an OI was 38% (n = 145/381). Antigen test positivity rate was 16% (72/467) for TB-LAM, 9% (43/464) for HisAg, and 11% (51/484) for CrAg. Twenty-one of 34 (62%) patients receiving CSF CrAg tests were positive, confirming meningitis. Significant differences in 30-day mortality were observed in patients with an OI (16%) vs. no OI (7%) (p = 0.002). Mortality was highest in patients with histoplasmosis (25%), co-infection (22%), cryptococcosis (18% overall; 19% for cryptococcal meningitis), and TB (10%). CONCLUSIONS: TB and fungal OIs, including co-infection, were common in PLHIV in Paraguay and had high associated mortality. Laboratories and health facilities need access to CD4 + T-cell testing and rapid diagnostic assays.

Preference for long-acting injectable for ART and PrEP among people with and without HIV: a cross-sectional study in Argentina.

Background: Little is known about the preferences for antiretroviral therapy (ART) administration methods, such as oral daily pills or long-acting injectable (LAI) options, as well as preferences for pre-exposure prophylaxis (PrEP) administration methods among people without HIV in Latin America. Objectives: This study aimed to assess the preferences for ART administration methods among people with HIV and PrEP methods among those without HIV, as well as to examine the correlations and reasons for these preferences. Design: We conducted a cross-sectional web-based questionnaire between April and July 2021, using social media accounts of a HIV non-governmental organization. The questionnaire was open to all adults living in Argentina, irrespective of their sexual orientation or gender identity. Methods: The questionnaire included questions on substance use, depression, chronic treatment, previous experiences with injectable medication, and HIV status. Those with HIV answered questions about ART adherence and their preferences for ART methods, while those without HIV were asked about condom use, awareness of PrEP, and their preferences for PrEP methods. Results: Out of 1676 respondents, 804 had HIV, and 872 did not. Among those with HIV, 91.5% expressed a high preference for LAI-ART, with significantly higher preferences among participants with higher educational levels, cisgender gay, bisexual, and queer men, younger individuals, and those with prior injectable medication experience. Among those without HIV, 68% preferred LAI-PrEP, and this preference was positively associated with previous positive experiences with injectable medication. Conclusion: The strong preference for LAI-ART suggests the potential for improved adherence and well-being among people with HIV. Additionally, the preference for LAI-PrEP among those without HIV emphasizes the importance of considering this option for HIV prevention strategies. This study highlights the need to offer diverse methods for ART and prevention to accommodate different preferences and improve health care outcomes in Latin America.

First case report of a perinatally HIV-infected infant with HIV resistance to dolutegravir associated with tenofovir/lamivudine/dolutegravir use in mothers.

Perinatally HIV-infected infants can be infected with a drug-resistant virus or select for drug resistance by exposure to sub-therapeutic levels of maternal antiretroviral drugs present in breastmilk or from sub-therapeutic infant prophylaxis. We report a case of dolutegravir resistance detected in a treatment-naive perinatally HIV-infected infant whose mother was receiving tenofovir/lamivudine/dolutegravir. This case was detected during a national survey of HIV drug resistance in Haiti amongst infants testing positive for HIV through the national early infant diagnosis program between April 2020 and March 2021. This unique case underscores the need for prompt management of high viral loads in pregnant and breastfeeding women and supports HIV drug resistance surveillance efforts targeted at antiretroviral therapy-naive infants born to mothers in low-and middle-income countries.

[Comparative analysis of clinical characteristics, evolution and mortality of hospitalized patients with COVID-19 during the first and second wave of the pandemic (ECCOVID Study)]. / Análisis comparativo de las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola de la pandemia (Registro ECCOVID).

INTRODUCTION: Clinical features and outcomes of SARSCoV-2 infections may change between different waves of the pandemic. The objective of this study was to compare clinical characteristics and outcomes between two cohorts of patients hospitalized for COVID-19 during the first and second waves in Argentina. METHODS: Multicenter and prospective registry of patients =18 years old with a confirmed diagnosis of COVID-19 admitted to 18 hospitals in Argentina during the first wave (March to October 2020) and second wave (March to July 2021) of the pandemic. Demographics, clinical characteristics, and outcomes of these patients were compared. RESULTS: A total of 1691 patients were included (first wave n = 809, second wave n = 882). Hospitalized patients during the second wave were older (median 53 years vs. 61 years, p < 0.001), had more comorbidities (71% vs. 77%, p=0.007) and required more supplemental oxygen at admission (21% vs 62%, p < 0.001). During hospitalization, patients of the second wave required more supplemental oxygen (49% vs. 85%, p < 0.001), invasive ventilation (12% vs. 22%, p < 0.001) and had higher 30- day mortality (11% vs. 26%, p < 0.001). Comparing only patients who required supplemental oxygen during hospitalization, 30-day mortality was 20% and 30% p < 0.001 for the first and second wave, respectively. CONCLUSION: Compared to patients admitted during the first wave, patients admitted with SARS-CoV2 during the second wave in Argentina were more seriously ill and had a higher mortality.

Introducción: Las características clínicas y evolutivas de los pacientes con diagnóstico de COVID-19 pueden diferir entre las distintas olas de la pandemia. El objetivo de este estudio fue comparar las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola en Argentina. Métodos: Registro multicéntrico y prospectivo de pacientes = 18 años con diagnóstico confirmado de COVID-19 internados en 18 hospitales de Argentina durante la primera (marzo a octubre 2020) y la segunda ola (marzo a julio 2021) de la pandemia. Se compararon variables demográficas, características clínicas, y evolución a 30 días. Resultados: Se incluyeron un total de 1691 pacientes (primera ola n = 809, segunda ola n = 882). Los pacientes hospitalizados durante la segunda ola tenían mayor edad (mediana 53 años vs. 61 años, p < 0.001), comorbilidades (71% vs. 77%, p = 0.007) y requerimiento de oxígeno (21% vs. 62%, p < 0.001). Durante la hospitalización, los pacientes de la segunda ola requirieron más oxigenoterapia (49% vs. 85%, p < 0.001), asistencia mecánica respiratoria (12% vs. 22%, p < 0,001) y presentaron mayor mortalidad (11% vs. 26%, p < 0.001). Comparando únicamente a los que requirieron oxigenoterapia durante la hospitalización, la mortalidad a los 30 días fue de 20% y 30% p < 0.001 en la primera y segunda ola respectivamente. Conclusión: Comparados con los pacientes internados durante la primera ola, los internados durante la segunda ola de SARS-CoV-2 en Argentina presentaron mayor gravedad y mortalidad.

Análisis comparativo de las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola de la pandemia (REGISTRO ECCOVID) / Comparative analysis of clinical characteristics, evolu tion and mortality of hospitalized patients with COVID-19 during the first and second wave of the pandemic (ECCOVID STUDY)

Resumen Introducción : Las características clínicas y evolutivas de los pacientes con diagnóstico de COVID-19 pueden diferir entre las distintas olas de la pandemia. El objetivo de este estudio fue comparar las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola en Argentina. Métodos : Registro multicéntrico y prospectivo de pacientes ≥ 18 años con diagnóstico confirmado de COVID-19 internados en 18 hospitales de Argentina durante la primera (marzo a octubre 2020) y la segunda ola (marzo a julio 2021) de la pandemia. Se compararon variables demográficas, características clínicas, y evolu ción a 30 días. Resultados : Se incluyeron un total de 1691 pacien tes (primera ola n = 809, segunda ola n = 882). Los pa cientes hospitalizados durante la segunda ola tenían mayor edad (mediana 53 años vs. 61 años, p < 0.001), comorbilidades (71% vs. 77%, p = 0.007) y requerimiento de oxígeno (21% vs. 62%, p < 0.001). Durante la hospi talización, los pacientes de la segunda ola requirieron más oxigenoterapia (49% vs. 85%, p < 0.001), asistencia mecánica respiratoria (12% vs. 22%, p <0,001) y presen taron mayor mortalidad (11% vs. 26%, p < 0.001). Compa rando únicamente a los que requirieron oxigenoterapia durante la hospitalización, la mortalidad a los 30 días fue de 20% y 30% p < 0.001 en la primera y segunda ola respectivamente. Conclusión : Comparados con los pacientes interna dos durante la primera ola, los internados durante la segunda ola de SARS-CoV-2 en Argentina presentaron mayor gravedad y mortalidad.

Abstract Introduction : Clinical features and outcomes of SARS-CoV-2 infections may change between different waves of the pandemic. The objective of this study was to compare clinical characteristics and outcomes between two cohorts of patients hospitalized for COVID-19 during the first and second waves in Argentina. Methods : Multicenter and prospective registry of patients ≥18 years old with a confirmed diagnosis of COVID-19 admitted to 18 hospitals in Argentina during the first wave (March to October 2020) and second wave (March to July 2021) of the pandemic. Demographics, clinical characteristics, and outcomes of these patients were compared. Results : A total of 1691 patients were included (first wave n = 809, second wave n = 882). Hospitalized pa tients during the second wave were older (median 53 years vs. 61 years, p < 0.001), had more comorbidities (71% vs. 77%, p=0.007) and required more supplemental oxygen at admission (21% vs 62%, p < 0.001). During hos pitalization, patients of the second wave required more supplemental oxygen (49% vs. 85%, p < 0.001), invasive ventilation (12% vs. 22%, p < 0.001) and had higher 30- day mortality (11% vs. 26%, p < 0.001). Comparing only patients who required supplemental oxygen during hos pitalization, 30-day mortality was 20% and 30% p < 0.001 for the first and second wave, respectively. Conclusion : Compared to patients admitted during the first wave, patients admitted with SARS-CoV2 dur ing the second wave in Argentina were more seriously ill and had a higher mortality.

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

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.

Mental health, substance use, experiences of violence, and access to health care among transgender and non-binary people during the COVID-19 lockdown in Argentina.

Background: Lockdown measures are effective to control COVID-19 spread; however, concerns have increased regarding its impact on transgender and non-binary people. Aims: This study describes self-reported changes in mental health, substance use, experiences of violence, and access to health care and basic services among transgender and non-binary population from Argentina after two months of implementation of the lockdown. Methods: An online national survey was responded by 182 participants (72 transfeminine [TF], 66 transmasculine [TM], 44 non-binary [NB] people) between May and June 2020. The questionnaire was informed by the results of focus groups, reviewed by activists, and disseminated through social media. Descriptive statistics were used to summarize data. Results: The COVID-19 pandemic and the lockdown have had a general negative impact on the participants. TF participants reported a greater proportion of negative changes in the socioeconomic aspect, such as reduction in income and barriers to access basic services (housing, food, hygiene products and financial assistance). TM and NB participants reported higher proportions of adverse psychological impact, with high frequencies of intense negative emotions and suicidal ideation. A general reduction in substance use was observed in the three groups. The most frequent source of violence in the three groups was from a family member, especially among NB participants. Half of the TF and TM individuals reported difficulties to access or continue their hormone therapy. TM and NB participants reported considerable barriers to access mental health care. Conclusion: The COVID-19 pandemic and the prolonged lockdown have had a negative impact on the transgender and NB population, aggravating their preexisting situation of vulnerability and exclusion. Furthermore, this impact affected each subgroup differently in a particular and specific way.

Identifying the needs of older people living with HIV (≥ 50 years old) from multiple centres over the world: a descriptive analysis.

BACKGROUND: Older People Living with HIV (OPWH) combine both aging and HIV-infection features, resulting in ageism, stigma, social isolation, and low quality of life. This context brings up new challenges for healthcare professionals, who now must aid patients with a significant comorbidity burden and polypharmacy treatments. OPWH opinion on their health management is hardly ever considered as a variable to study, though it would help to understand their needs on dissimilar settings. METHODS: We performed a cross-sectional, comparative study including patients living with HIV aged ≥50 years old from multiple centers worldwide and gave them a survey addressing their perception on overall health issues, psychological problems, social activities, geriatric conditions, and opinions on healthcare. Data was analyzed through Chisquared tests sorting by geographical regions, age groups, or both. RESULTS: We organized 680 participants data by location (Center and South America [CSA], Western Europe [WE], Africa, Eastern Europe and Israel [EEI]) and by age groups (50- 55, 56-65, 66-75, >75). In EEI, HIV serostatus socializing and reaching undetectable viral load were the main problems. CSA participants are the least satisfied regarding their healthcare, and a great part of them are not retired. Africans show the best health perception, have financial problems, and fancy their HIV doctors. WE is the most developed region studied and their participants report the best scores. Moreover, older age groups tend to live alone, have a lower perception of psychological problems, and reduced social life. CONCLUSIONS: Patients' opinions outline region- and age-specific unmet needs. In EEI, socializing HIV and reaching undetectable viral load were the main concerns. CSA low satisfaction outcomes might reflect high expectations or profound inequities in the region. African participants results mirror a system where general health is hard to achieve, but HIV clinics are much more appealing to them. WE is the most satisfied region about their healthcare. In this context, age-specific information, education and counseling programs (i.e. Patient Reported Outcomes, Patient Centered Care, multidisciplinary teams) are needed to promote physical and mental health among older adults living with HIV/AIDS. This is crucial for improving health-related quality of life and patient's satisfaction.

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.

"If I'm at home, I do it at home": Qualitative study on HIV self-testing among transgender women in Argentina.

BACKGROUND: Evidence among key populations supports acceptability of HIV self-testing (HIVST) due to its privacy and convenience. However, insufficient research has been done among transgender women (TGW), especially in Latin America. Consequently, the aim of this study was to explore the acceptability, perceptions and recommendations for HIVST implementation among TGW in Buenos Aires. METHODS: A focus group was conducted in July 2019. Particpants were invited to touch and learn about a displayed HIVST kit. The following main topics were explored: acceptability, reasons for seeking self-testing, preferences for training, distribution, periodicity and recommendations for HIVST implementation. RESULTS: The sample consisted of 12 TGWs; mean age of 26 years (IQR = 22-28); 66% had history of sex-work. The main motivations for seeking HIVST were convenience, privacy, and usage to reduce stigma and discrimination by health-care providers. Recommendations for HIVST were: distribution from primary health centers and trans-sensitive centers; affordable price; assistance by peer health promoters; and the provision of clear written and video instructions. CONCLUSIONS: Tailored implementation of HIVST can increase HIV testing rates, early detection, and linkage to HIV-care in this high-prevalence group. This study provided community-driven suggestions to inform and adapt an HIVST feasibility pilot study and future implementation in Argentina.

Assessing the Underestimation of HIV Risk Infection among Young Men Who Have Sex with Men in Argentina.

The aim of this study is to describe the discordance between the self-perceived risk and actual risk of HIV among young men who have sex with men (YMSM) and its associated factors. An online, cross-sectional study was conducted with 405 men recruited from an Argentinian NGO in 2017. Risk discordance (RD) was defined as the expression of the underestimation of risk, that is, as a lower self-perception of HIV risk, as measured with the Perceived Risk of HIV Scale, than the current risk of HIV infection, as measured by the HIV Incidence Risk Index. Multivariate logistic regression models were used to analyze the associations between the RD and the explanatory variables. High HIV risk was detected in 251 (62%), while 106 (26.2%) showed high self-perceived risk. RD was found in 230 (56.8%) YMSM. The predictors that increased RD were consistent condom use with casual partners (aOR = 3.8 [CI 95:1.5-11.0]), the use of Growler to meet partners (aOR = 10.38 [CI 95:161-121.94]), frequenting gay bars (aOR = 1.9 [95% CI:1.1-3.5]) and using LSD (aOR = 5.44 [CI 95:1.32-30.29]). Underestimation of HIV risk in YMSM is associated with standard HIV risk behavior and modulated by psychosocial aspects. Thus, prevention campaigns aimed at YMSM should include these factors, even though clinical practice does not. Health professionals should reconsider adapting their instruments to measure the risk of HIV in YMSM. It is unknown what score should be used for targeting high-risk YMSM, so more research is needed to fill this gap. Further research is needed to assess what score should be used for targeting high-risk in YMSM.

A small cluster randomised clinical trial to improve health outcomes among Argentine patients disengaged from HIV care.

Background: Patients disengaged from HIV care, e.g., missed medication pick-ups, not attending physician visits, account for ≥70% of new HIV infections. Re-engaging and sustaining engagement is essential to controlling the HIV pandemic. This study tested a physician-delivered evidence-based intervention, Motivational Interviewing (MI), to improve health outcomes, adherence to antiretroviral therapy (ART), HIV virologic suppression, CD4+ count, retention in HIV care, and self-efficacy among patients disengaged from care in Argentina. Methods: Regional clinics (n = 6) were randomised to condition, MI Intervention or Enhanced Standard of Care (ESOC), and recruited N = 360 patients disengaged from HIV care. ART adherence, HIV RNA viral load, CD4+ count retention, and self-efficacy were assessed at baseline, 6, 12, 18, and 24-months. Indirect effects from condition to main outcomes were examined using patient-provider relationship as a mediator. The study was a cluster-randomised clinical trial entitled Conexiones y Opciones Positivas en la Argentina 2 (COPA2) and was registered at clinicaltrials.gov, NCT02846350. Findings: Participants were an average age of 39·15 (SD = 10·96), 51% were women; intervention participants were older (p = ·019), and more ESOC participants were women (60% vs. 42%, p = 0·001). Using mixed models, the intervention had no effect on ART adherence over time by condition on HIV RNA viral load, CD4+ count retention, or self-efficacy. However, analysing mediated paths, there was an indirect effect of condition on ART adherence (B = 0·188, p = 0·009), HIV viral load (B = -0·095, P = 0·027), and self-efficacy (B = 0·063, P = 0·001), suggesting the intervention was associated with improved patient-provider relationships, which was in turn associated with increased ART adherence, lower HIV viral load, and higher self-efficacy. Interpretation: These findings suggest that physician-delivered MI may enhance the patient-provider relationship, self-efficacy, and ART adherence, and reduced HIV viral load in patients disengaged from HIV care. However, these findings are preliminary due to the small number of clusters randomised, and replication is warranted. Funding: National Institutes of Health.

A Dynamic Interplay of Circulating Extracellular Vesicles and Galectin-1 Reprograms Viral Latency during HIV-1 Infection.

Combined Antiretroviral therapy (cART) suppresses HIV replication but fails to eradicate the virus, which persists in a small pool of long-lived latently infected cells. Immune activation and residual inflammation during cART are considered to contribute to viral persistence. Galectins, a family of ß-galactoside-binding proteins, play central roles in host-pathogen interactions and inflammatory responses. Depending on their structure, glycan binding specificities and/or formation of distinct multivalent signaling complexes, different members of this family can complement, synergize, or oppose the function of others. Here, we identify a regulatory circuit, mediated by galectin-1 (Gal-1)-glycan interactions, that promotes reversal of HIV-1 latency in infected T cells. We found elevated levels of circulating Gal-1 in plasma from HIV-1-infected individuals, which correlated both with inflammatory markers and the transcriptional activity of the reservoir, as determined by unspliced-RNA (US-RNA) copy number. Proinflammatory extracellular vesicles (EVs) isolated from the plasma of HIV-infected individuals induced Gal-1 secretion by macrophages. Extracellularly, Gal-1 interacted with latently infected resting primary CD4+ T cells and J-LAT cells in a glycan-dependent manner and reversed HIV latency via activation of the nuclear factor κB (NF-κB). Furthermore, CD4+ T cells isolated from HIV-infected individuals showed increased HIV-1 transcriptional activity when exposed to Gal-1. Thus, by modulating reservoir dynamics, EV-driven Gal-1 secretion by macrophages links inflammation with HIV-1 persistence in cART-treated individuals. IMPORTANCE Antiretroviral therapy has led to a dramatic reduction in HIV-related morbidity and mortality. However, cART does not eradicate the virus, which persists in resting CD4+ T cells as the main viral reservoir, consequently requiring lifelong treatment. A major question is how the functional status of the immune system during antiretroviral therapy determines the activity and size of the viral reservoir. In this study, we identified a central role for galectin-1 (Gal-1), a glycan-binding protein released in response to extracellular vesicles (EVs), in modulating the activity of HIV reservoir, thus shaping chronic immune activation in HIV-infected patients. Our work unveils a central role of Gal-1 in linking chronic immune activation and reservoir dynamics, highlighting new therapeutic opportunities in HIV infection.

HIV and aging, biological mechanisms, and therapies: What do we know?

Aging, a time-dependent loss of physiological function, and its drivers are turning into a significant topic of researchas the population's mean age increases. Epigenetic alterations, telomere shortening or dysfunction, mitogenic stress,oxidative stress, or accumulation of DNA damage can drive the cell to senescence a permanent cell cycle arrest sometimes associated with a secretory phenotype and inflammatory consequences in the surrounding tissue. The amount of senescent cellsgrows over time in older organisms and may induce tissue inflammation and threaten overall tissue homeostasis, favoring aging. Senolytic and senomorphic therapeuticsare an emerging approach to eliminate senescent cells or to block their secretoryphenotypes respectively. Given that people living with HIV suffer non-AIDS comorbidities in a higher prevalence than the general population, aging is accentuated among them. Inflammation biomarkers may be helpful to assess prognosis or act as surrogate endpoints for studies of strategies focused on reversal of HIV-associated accelerated aging. This review summarizes the latest findings in aging and its major drivers, under the light of HIV infection. Since the number of older PLWH is currently rising, it will be of great importance to address and treat their age-related conditions, as well as to better decipher their biological mechanisms.

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.

Prevention and Treatment of SARS-CoV2 Infection in People Living with HIV: The Need for Specific Data.

The HIV pandemic has led to close to 40 million people living with HIV (PLWH) worldwide. To date, SARS-CoV2 has affected > 220 million people, and unprecedented global efforts have resulted in almost 6000 million doses of SARS-CoV2 vaccines being administered. Although several specific COVID-19 antiviral and anti-inflammatory treatments and SARS-CoV2 vaccines have been approved, the data available to support their use in specific populations such as PLWH remain limited. PLWH includes a range of individuals from practically unaffected immunity to severely immunocompromised individuals, and preventive and therapeutic interventions should be tailored for these subgroups . However, in most randomized clinical trials regarding antivirals, immunomodulators and vaccines for COVID-19, PLWH have been excluded or only enrolled in small numbers leading to a paucity of data. We briefly discuss the current evidence for prevention and treatment of COVID-19 in PLWH and identify key areas where more information is required.