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Objectives Early initiation of antiretroviral therapy (ART) during acute HIV infection is associated with favourable clinical and epidemiological outcomes. Barriers to prompt treatment initiation limit the benefits of universal access to ART in Mexico. We sought to create an algorithm for the immediate detection and treatment of patients with acute HIV infection. Methods A nationwide cohort of patients with acute HIV infection was created in 2015. In order to identify cases and treat them promptly at our centre, an interdisciplinary group coordinated through an instant-messaging tool using smart phones was established. When a probable case was detected, a discussion was initiated to confirm the diagnosis and facilitate the administrative processes to initiate ART as soon as possible. We compared time to ART initiation with that in a comparison group of patients with chronic HIV infection enrolled during the same period (May 2015 to February 2017) through routine care, using survival analysis estimators and log-rank tests. Results We recruited 29 patients with acute HIV infection. The median time to ART initiation was 2 days in these patients, in contrast to 21 days for patients with chronic infection. There were no significant differences in the percentages of patients engaged in care, on treatment or virologically suppressed at 1 year of follow-up. Conclusions Implementing immediate ART initiation programmes is feasible in Mexico, in spite of the substantial administrative barriers that exist in the country. More extensive replication of this model in other centres and in patients with chronic infection is warranted to evaluate its effect on the continuum of care.

Background The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283220SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine. Methodology/Principal findings We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78–30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4–76.2) / 96.2% (95% CI, 93.2–98.0) for IAHE, 91.3% (95% CI, 84.2–96.0) / 90.9% (95% CI, 87.0–94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0–95.3) / 92.3% (95% CI, 88.6–95.1) for MVHUALFA. The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3–72.5)/ 89.5% (95%CI, 86.0–93.0), 65.9% (95%CI, 56.0–75.8)/ 89.0% (95%CI, 85.2–92.9), 62.1% (95%CI, 44.4–79.7)/ 82.6% (95%CI, 71.7–93.6) and 34.9% (95%CI, 24.8–46.2)/ 67.3% (95%CI, 60.6–73.5) respectively; and 1281-1283220SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9–74.7)/ 58.8% (95%CI, 53.2–64.5), 70.8% (95%CI, 61.3–80.2)/ 52.9% (95%CI, 46.8–59.1), 71.4% (95%CI, 54.7–88.2)/ 40.4% (95%CI, 26.4–54.5) and 18.1% (95%CI, 10.5–28.1)/ 90.4% (95%CI, 85.5–94.0), respectively. Conclusions/Significance The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment., Author summary Histoplasmosis, an infection caused by Histoplasma capsulatum, is prevalent in the Americas, it is a common cause of pulmonary acute disease in cave explorers, speleologists, boy scouts and some other people in circumstantial risk, in most of these people the infection is commonly self-limited. However, in people living with HIV (PLWHIV) this infection might be acquired without specific exposition and it behaves like a severe disease with high fever, consumption, septic shock and death. Thus, there is a need for rapid and accurate methods for diagnosis in this population at risk. We tested five different methods for rapid diagnosis (three based on antigen detection in urine and two molecular assays based on PCR amplification, widely used) of disseminated histoplasmosis and we were able to demonstrate that two urine antigen detection tests (clarus Histoplasma GM Enzyme Immunoassay kit and MiraVista Histoplasma Urine Antigen LFA) showed excellent performance to diagnose of disseminated histoplasmosis in PLWHIV. The antigen detection tests have advantages over the PCR tests, their performance is higher, they are commercial standardized tests, easy to perform, and provide results in hours, therefore the integration of these tests in clinical laboratories will certainly impact on early diagnosis/treatment and consequently on the outcome of patients.

Background The Histoplasma urine antigen (HUAg) is the preferred method to diagnose progressive disseminated histoplasmosis (PDH) in HIV patients. In 2007, IMMY ALPHA Histoplasma EIA was approved for clinical for on-site use, and therefore useful for regions outside the United States. However, ALPHA-HUAg is considered inferior to the MVista-HUAg which is only available on referral. We aim to evaluate the diagnostic accuracy of ALPHA-HUAg. Methodology/Principal findings We conducted a multicenter, prospective, diagnostic test study in two secondary and eight tertiary-care facilities in Mexico. We included HIV patient with PDH suspicion and evaluated ALPHA-HUAg diagnostic accuracy using as reference standard the Histoplasma capsulatum growth on blood, bone marrow, and tissue cultures or compatible histopathologic exam (PDH–proven). We evaluated the results of 288 patients, 29.5% (85/288; 95% confidence interval [CI], 24.3–35.1) had PDH. The sensitivity of ALPHA-HUAg was 67.1% (95% CI, 56–76.8%) and the specificity was 97.5% (95% CI, 94.3%-99.1%). The positive likelihood ratio was 27.2 (95% CI; 11.6–74.4). In 10.5% of the PDH–proven patients, a co-existing opportunistic infection was diagnosed, mostly disseminated Mycobacterium avium complex infection. Conclusions/Significance We observed a high specificity but low sensitivity of IMMY-HUAg. The test may be useful to start early antifungals, but a culture-based approach is necessary since co-infections are frequent and a negative IMMY-HUAg result does not rule out PDH., Author summary Histoplasmosis is an endemic mycosis in many regions of Latin America. In the HIV population it manifests as progressive disseminated histoplasmosis (PDH), an entity hard to diagnose since the causative fungi—Histoplasma capsulatum—is slow growing and requires advance biosafety for its handling. As an alternative, the diagnosis can be made by detecting the histoplasma urinary antigen, but only one kit is commercially available outside the US. We evaluated this kit (IMMY ALPHA Histoplasma EIA) among HIV patients with suspected and found a high specificity but low sensitivity (i.e., a positive histoplasma urine antigen is almost unequivocal, but a negative result does not rule out the PDH). However, we believe the test is useful since the positive likelihood rates show that a patient with PDH is 27 times more likely to have an IMMY-HUAg positive result; this may allow early targeted treatment.

Background ARV treatment (ART) administered during acute HIV-infection presents several immunological benefits leading to a better CD4+ T-cell recovery and a diminished HIV reservoir. Methods Patients with acute HIV-infection, enrolled in the VIHIA cohort, had blood samples taken at diagnosis and at 2, 6 and 12 months after ART initiation. Flow-cytometry analysis was performed in fresh whole blood. Naïve-(Nv), central memory (CM), effector memory (EM) and terminally differentiated T-cells (TMRA), as well as activation markers were defined using CD3, CD4, CD8, CD45RA, CCR7, CD38, CD31 and HLA-DR markers. CD28 and CD57 were used to identify immunosenescent cells. Fox-P3, CD 25, CD127 and CD45RA were used to identify Regulatory T cells (Treg) and their subsets. To assess changes over time, Wilcoxon-matched-pairs signed rank test was used for each value between baseline and months 2 and 12 independently. Results Four patients were diagnosed at Fiebig stage II; 5 patients at Fiebig stage III, 24 patients at stage IV and 5 patients in stage V. All patients received treatment within the first 24 hours of HIV diagnosis. Only 13 patients had flow-cytometry data at baseline and 1 year of follow-up. All subjects were MSM with a mean age of 32 y.o. Mean CD4+ T-cell count was 439 cells/μL and mean viral load was 1.2 million copies/mL (23,379–10 × 106 copies/mL) at baseline. The change in T-cell differentiation patterns at 0 and 12 months is shown in Figure 1. Activation markers decreased in all studied subsets at 2 months and furthermore at 12 months. Total T-regs increased from 5.1% to 7.8% at 1 year of follow-up (Figure 2). Immunosenescence markers increased steadily throughout the study in all T-cell subsets, being statistically significant in the total T-cell CD8 population at 12 months of follow-up (Figure 3) unrelated to Fiebig stage. Conclusion It has been hypothesized that early ART decreases T-cell immunosenescence; however, in our cohort despite treatment during acute HIV, we observed that at 1 year follow-up immunosenescence markers increased despite a decrease in immune activation and a recovery of T-cell subsets. Disclosures All authors: No reported disclosures.

Objetivo. Determinar las características clínicas y epidemiológicas de los casos con tuberculosis (TB) activa en población de cárceles con VIH, que se ve especialmente afectada por ambas epidemias. La infección por VIH incrementa significativamente la probabilidad del desarrollo de TB. Material y métodos. Se realizó un estudio de cohorte en sujetos infectados por VIH e internados en un reclusorio de la Ciudad de México. Resultados. Se encontraron 172 pacientes con VIH, 28 con TB activa (16.3%) 21 (12.2%) con afección pulmonar con una tasa de incidencia de 7.7 por 100 sujetos/año para TB activa y de 4.7 por 100 sujetos/ año para TB pulmonar. No se encontró drogorresistencia. Dieciocho aislados fueron tipificados por RFLP, con una tasa de transmisión calculada de 11%. Conclusión. Se encontró una prevalencia de TB en esta población mil veces superior a la observada en la población general y datos sugerentes de transmisión al interior de la cárcel.

To determine the clinical and epidemiological characteristics of prison inmates with active tuberculosis in HIV-positive prison populations.We conducted a cohort study in HIV-infected subjects in a prison in Mexico City, with the aim of determining clinical and epidemiological characteristics of cases with active TB.We detected 172 HIV infected inmates and TB in 28 of them (16.3%) - 21 (12.2) with pulmonary TB--with an incidence rate of 7.7/100 persons/year for active TB and 4.7/100 persons/year for pulmonary TB. No drug resistance was found. Two clusters (4 and 2 subjects) were observed after RFLP-typing of 18 isolates, with a transmission rate of 11% by molecular and clinical analysis.The prevalence of active TB was found to be a thousand times greater than in the general population. Evidence of transmission inside the prison was also found.