Characteristics and outcomes of people living with HIV hospitalised at tertiary healthcare institutions during the COVID-19 pandemic in Mexico City.

BACKGROUND: While existing research on people living with HIV (PWH) during the COVID-19 pandemic primarily focused on their clinical outcomes, a critical gap remains in understanding the implications of COVID-19 delivery of in-hospital care services to PWH. Our study aimed to describe the characteristics and outcomes of PWH hospitalised during 2020 in Mexico City, comparing patients admitted due to COVID-19 vs. patients admitted due to other causes. METHODS: All PWH hospitalised for ≥ 24 h at four institutions in Mexico City from January 1st to December 31st, 2020 were included. Patients were classified into two groups according to the leading cause of their first hospitalisation: COVID-19 or non-COVID-19. Characteristics among groups were compared using chi-square and Kruskal tests. A Cox model was used to describe the risk of death after hospitalisation and the characteristics associated with this outcome. Mortality and hospitalisation events were compared to data from 2019. RESULTS: Overall, we included 238 PWH hospitalised in 2020. Among them, 42 (18%) were hospitalised due to COVID-19 and 196 (82%) due to non-COVID-19 causes, mainly AIDS-defining events (ADE). PWH hospitalised due to COVID-19 had higher CD4 + cell counts (380 cells/mm3 [IQR: 184-580] vs. 97 cells/mm3 [IQR: 34-272], p < 0.01) and a higher proportion of virologic suppression (VS) compared to those hospitalised due to non-COVID-19 causes (92% vs. 55%, p < 0.01). The adjusted hazard ratio (aHR) for AIDS was 3.1 (95%CI: 1.3-7.2). COVID-19 was not associated with death (aHR 0.9 [95%CI: 0.3-2.9]). Compared to 2019, mortality was significantly higher in 2020 (19% vs. 9%, p < 0.01), while hospitalisations decreased by 57%. CONCLUSIONS: PWH with COVID-19 had higher VS and CD4 + cell counts and lower mortality compared to those hospitalised due to non-COVID-19-related causes, who more often were recently diagnosed with HIV and had ADEs. Most hospitalisations and deaths in 2020 in PWH were related to advanced HIV disease. The increased mortality and decreased hospitalisations of PWH during 2020 evidence the impact of the interruption of health services delivery for PWH with advanced disease due to the pandemic. Our findings highlight the challenges faced by PWH during 2020 in a country where advanced HIV remains a concern.

The vaginal microbiota of women living with HIV on suppressive antiretroviral therapy and its relation to high-risk human papillomavirus infection.

BACKGROUND: Few studies have investigated the vaginal microbiota (VM) in women living with HIV (WLWH) in the context of high-risk human papillomavirus (HR-HPV) infection, even though WLWH are at an increased risk of HPV-related malignancies, including cervical cancer. To explore the impact of HIV and HPV infection on the VM in WLWH, we determined the prevalence of HR-HPV infection and cervical cytologic abnormalities in a cohort of 44 WLWH and 39 seronegative-women (SNW), characterized the vaginal microbiota by 16S sequencing, assessed genital inflammation and systemic immune activation by multiplex bead assay and flow cytometry, respectively. Finally, we explored relationships between bacterial richness and diversity, the top 20 bacterial genera, genital inflammation and systemic immune activation. RESULTS: We found that HR-HPV prevalence was similar between WLWH and SNW. High-grade squamous intraepithelial lesions (HSIL) were only detected in WLWH negative for HR-HPV infection. In regression analyses, no risk factors were identified. Women co-infected with HIV and HR-HPV had the highest level of systemic immune activation, and these levels were significantly different compared with SNW without HR-HPV infection. Lactobacillus iners was the dominant Lactobacillus species in WLWH and SNW alike. CONCLUSION: We found no evidence of differences in vaginal microbial richness and diversity, microbial community structure, and genital inflammation by HIV, HPV, or HIV and HPV status.

Double-Negative T Cell Number and Phenotype Alterations Before and After Effective Antiretroviral Treatment in Persons Living with HIV.

Double-negative (DN) T cells represent a small and phenotypically heterogeneous population that display regulatory functions. In HIV infection, DN T cells are decreased in peripheral blood and have been negatively associated with T cell activation. This study was aimed at describing the dynamics and phenotypic characteristics of DN T cells in peripheral blood of people living with HIV (PLHIV) before and after antiretroviral therapy (ART) initiation. We included 41 newly diagnosed, ART-naive individuals with advanced HIV infection, who were followed up for 6 months after ART initiation. The control group included 34 people without HIV (PWHIV), on preexposure prophylaxis for HIV infection. DN T cells in peripheral blood were characterized by flow cytometry. The absolute counts of DN T cells were lower in PLHIV than in PWHIV (p = 0.0223), and were particularly low in individuals with advanced HIV disease (p = 0.0311). Activation of DN T cells before ART initiation was directly associated with viral load (VL) (p = 0.0081, r = 0.4083) and inversely associated with CD4+ T cell counts (p = 0.0004, r = -0.4041). Compared with PWHIV, DN T cells of PLHIV expressed higher levels of CD57 (p = 0.0019), Ki67 (p = 0.0065), PD-1 (p = 0.0187), and CD38/HLA-DR (p < 0.0001). After 6 months on ART, expression of Ki67, PD-1, and CD38/HLA-DR on DN T cells returned to similar levels to those observed in PWHIV (p > 0.05 in all cases). However, expression of CD57 decreased only in individuals that start ART with high VL (p = 0.0127). DN T cell counts are decreased in HIV infection. Low DN T cell counts remained despite ART-induced immune reconstitution and viremia control. DN T cell phenotype is altered during chronic untreated infection with a high proportion of proliferating, activated, exhausted, and senescent cells. Most markers return to levels similar to those observed in PWHIV after ART. The impact of altered phenotype of DN T and their regulatory functions warrants further exploration.

Characterization of CD31 expression in CD4+ and CD8+T cell subpopulations in chronic untreated HIV infection.

BACKGROUND: The platelet endothelial cell adhesion molecule-1 (PECAM-1) or CD31 has been involved in regulation of T-cell tolerance, activation, survival and homing in mice cells. However, there is limited knowledge about the expression pattern and role of this molecule in human T cells, particularly in conditions of chronic immune activation. OBJECTIVES: We explored CD31 expression in T cell differentiation subsets of individuals with untreated HIV infection and in non-HIV-infected controls. We also assessed phenotypic differences between CD31+ and CD31- subsets in memory and terminally differentiated (TEMRA) CD4+ and CD8 + T cells. METHODS: Forty-one individuals with untreated HIV infection and 34 non-HIV-infected controls were included in the study. We compared the expression of CD31 in CD4+ and CD8 + T cells across stages of differentiation in the two study groups by flow cytometry. We also analyzed the expression of CD57 (a marker of senescence), Ki67 (a marker of cycling cells), PD-1 (a marker of exhaustion), and CD38/HLA-DR (a marker of immune activation) on memory and TEMRA CD31+ and CD31- T cells. RESULTS: CD31 expression was significantly higher in CD8 + T cells than in CD4 + T cells, measured as frequency, absolute numbers and median fluorescence intensity (MFI), in both study groups (p < 0.0001 in all cases). Intermediate differentiation subsets of CD4+ and CD8 + T cells expressed higher levels of CD31 in the context of HIV infection (p < 0.001 in all cases). CD31 expression frequency decreased with cellular differentiation of CD4+ and CD8 + T cells in both groups, but this decrease was steeper in individuals without HIV infection (CD4+: p < 0.001 and CD8+: p < 0.0001). As expected, memory and TEMRA CD4+ and CD8 + T cells expressed significantly higher levels of CD57, PD-1, Ki67 and CD38/HLA-DR in HIV-infected compared to non-HIV-infected individuals (p < 0.01 in all cases). CD31 expression was associated with lower activation of memory (but not TEMRA) CD4 + T cells in non-HIV-infected persons, an effect not observed in the HIV-infected group. CD31 expression on memory CD8 + T cells of HIV-infected individuals was associated higher levels of PD-1 (p = 0.0019) and CD38/HLADR (p = 0.0345), and higher PD-1 expression on CD8 + TEMRA (p = 0.0024), an effect not observed in non-HIV-infected individuals. CONCLUSION: In the context of HIV-associated chronic immune activation, specifically on memory CD8 + T cells, CD31 expression was associated with higher PD-1 and CD38/HLA-DR co-expression, suggesting that CD31 expression may result from an insufficient attempt to contain T cell exhaustion and activation. CD31-targeted therapies may contribute to modulate these cellular responses.

Associations between recent thymic emigrants and CD4+ T-cell recovery after short-term antiretroviral therapy initiation.

OBJECTIVE: Around 20-30% of HIV-infected individuals (HIV+) on successful antiretroviral therapy (ART) fail to normalize their CD4 T-cell counts. Various factors could contribute to the lack of immune reconstitution, one of them being thymic insufficiency. We aimed to explore associations between recent thymic emigrants (RTEs) and CD4 T-cell recovery. DESIGN: ART-naive HIV+ individuals who started ART with advanced AIDS were selected. Good versus poor immune reconstitution was defined by CD4 gains above or below 100 CD4 T cells/µl. The follow-up period was 6 months. METHODS: Peripheral blood mononuclear cells were isolated and flow cytometry was used to characterize RTEs as the fraction of naive CD4 T cells expressing CD31, the platelet endothelial cell adhesion molecule. Markers of cellular activation, senescence, exhaustion and cycling were also assessed. RESULTS: After 6 months on ART, HIV+ individuals with good immune reconstitution had higher absolute numbers of RTEs, compared with those with poor immune reconstitution, and these strongly correlated with CD4 gains in those individuals with good immune reconstitution but not with poor immune reconstitution. We also found that CD8 T-cell immune activation decreased as early as 2 months post-ART initiation in individuals with good immune reconstitution, but only at month 6 post-ART in individuals with poor immune reconstitution. Levels of immune activation were inversely correlated with the absolute numbers of RTEs in both groups, but more strongly so in individuals with poor immune reconstitution. CONCLUSION: We show that RTEs are linked to CD4 T-cell recovery and that the degree of immune reconstitution is not directly linked to persistent immune activation.

Prevalence and risk factors for oral human papillomavirus infection in Mexican HIV-infected men / Prevalencia y factores de riesgo para infección oral con virus de papiloma humano en hombres mexicanos con VIH

Abstract: Objective: To determine the prevalence and risk factors for oral high-risk human papillomavirus (HR-HPV) infection in human immunodeficiency virus(HIV)-infected men. Materials and methods: Consecutive male outpatients with HIV-infection were enrolled. Demographic and behavioral risk data were obtained. Anal swabs and oral rinses were tested for HR-HPV DNA. Oral, pharyngeal and video laryngoscopy examinations were performed for detection of lesions. Results: The prevalence of HR-HPV oral infection was 9.3% (subtypes other than HR HPV 16/18 predominated). The prevalence of anal HR-HPV infection was 75.7%. The risk factors for oral infection with HR-HPV were tonsillectomy (OR=13.12) and years from HIV diagnosis (OR=1.17). Conclusions: Tonsillectomy and years from HIV diagnosis were associated with oral HPV infection. No association was found between oral and anal HR-HPV infections. This is the first study reporting the prevalence and risk factors for oral HR-HPV infection in Mexican HIV-infected population.

Resumen: Objetivo: Determinar la prevalencia y los factores de riesgo para infección oral por virus de papiloma humano de alto riesgo (VPH-AR) en individuos con VIH. Material y métodos: Se incluyeron pacientes ambulatorios consecutivos con VIH. Se recabó información demográfica y sobre factores de riesgo conductuales. Se detectó DNA de VPH-AR en hisopado rectal y enjuague bucal. Se efectuó exploración de boca, faringe y videolaringoscopía para detectar lesiones. Resultados: La prevalencia de VPH-AR oral fue 9.3% (predominaron subtipos diferentes de VPH-AR 16/18). La prevalencia de VPH-AR anal fue 75.7%. Los factores de riesgo para VPH-AR oral fueron la tonsilectomía (OR=13.12) y los años de diagnóstico del VIH (OR=1.17). Conclusiones: La tonsilectomía y los años de diagnóstico del VIH se asociaron con VPH-AR oral. No hubo asociación entre VPH-AR oral y anal. Este es el primer reporte sobre prevalencia y factores de riesgo para VPH-AR oral en población mexicana con VIH.

Prevalence and risk factors for oral human papillomavirus infection in Mexican HIV-infected men.

OBJECTIVE: To determine the prevalence and risk factors for oral high-risk human papillomavirus (HR-HPV) infec- tion in human immunodeficiency virus(HIV)-infected men. MATERIALS AND METHODS: Consecutive male outpatients with HIV-infection were enrolled. Demographic and behav- ioral risk data were obtained. Anal swabs and oral rinses were tested for HR-HPV DNA. Oral, pharyngeal and video laryngoscopy examinations were performed for detection of lesions. RESULTS: The prevalence of HR-HPV oral infection was 9.3% (subtypes other than HR HPV 16/18 predominated). The prevalence of anal HR-HPV infection was 75.7%. The risk factors for oral infection with HR-HPV were tonsillectomy (OR=13.12) and years from HIV diagnosis (OR=1.17). CONCLUSIONS: Tonsillectomy and years from HIV diagnosis were associated with oral HPV infection. No association was found between oral and anal HR-HPV infections. This is the first study reporting the prevalence and risk factors for oral HR-HPV infection in Mexican HIV-infected population.

OBJETIVO: Determinar la prevalencia y los factores de riesgo para infección oral por virus de papiloma humano de alto ries- go (VPH-AR) en individuos con VIH. MATERIAL Y MÉTODOS: Se incluyeron pacientes ambulatorios consecutivos con VIH. Se recabó información demográfica y sobre factores de riesgo conductuales. Se detectó DNA de VPH-AR en hisopado rectal y enjuague bucal. Se efectuó exploración de boca, faringe y videolaringoscopía para detectar lesiones. RESULTADOS: La prevalencia de VPH-AR oral fue 9.3% (predominaron subtipos diferentes de VPH-AR 16/18). La prevalencia de VPH-AR anal fue 75.7%. Los factores de riesgo para VPH-AR oral fueron la tonsilectomía (OR=13.12) y los años de diagnóstico del VIH (OR=1.17). CONCLUSIONES: La tonsilectomía y los años de diagnóstico del VIH se asociaron con VPH-AR oral. No hubo asociación entre VPH-AR oral y anal. Este es el primer reporte sobre prevalencia y factores de riesgo para VPH-AR oral en población mexicana con VIH.

HIV pretreatment drug resistance trends in three geographic areas of Mexico.

BACKGROUND: Pretreatment drug resistance (PDR) levels to NNRTI approaching 10% have recently been reported in Mexico. However, subnational differences may exist in PDR prevalence and transmission dynamics. OBJECTIVES: We longitudinally assessed HIV PDR in three geographic areas of Mexico. PATIENTS AND METHODS: HIV-infected, antiretroviral-naive individuals were recruited from 2008 to 2016, from the Central Metropolitan Zone (CMZ), Cancun and Tijuana (1194, 773 and 668 respectively). PDR was estimated using the Stanford HIVdb tool from plasma HIV pol sequences. RESULTS: A higher proportion of females, lower education and lower employment rate were observed in Tijuana, while a higher proportion of MSM was observed in the CMZ (P < 0.0001, all cases). For 2012-16, PDR was 13.4%, 8.9% and 11.2% in the CMZ, Tijuana and Cancun respectively. NNRTI PDR was highest in the three regions (8.7%, 4.8% and 8.1% respectively, P < 0.05); nevertheless, NNRTI PDR in Tijuana was lower than in the CMZ (P = 0.01). For 2008-16, we observed increasing efavirenz resistance trends in all regions (P < 0.05, all cases), reaching 11.8%, 6.1% and 8.3% respectively in 2016. Increasing efavirenz resistance was mostly associated with increasing K103N frequency (P = 0.007 CMZ, P = 0.03 Tijuana, not significant for Cancun). CONCLUSIONS: Our study suggests different NNRTI PDR prevalence and transmission dynamics in three geographical areas of Mexico. Even when increasing trends in efavirenz resistance were observed in the three areas, our observations support that, in a large country such as Mexico, subnational surveillance and locally tailored interventions to address drug resistance may be a reasonable option.

Pretreatment HIV-drug resistance in Mexico and its impact on the effectiveness of first-line antiretroviral therapy: a nationally representative 2015 WHO survey.

BACKGROUND: WHO has developed a global HIV-drug resistance surveillance strategy, including assessment of pretreatment HIV-drug resistance. We aimed to do a nationally representative survey of pretreatment HIV-drug resistance in Mexico using WHO-recommended methods. METHODS: Among 161 Ministry of Health antiretroviral therapy (ART) clinics in Mexico, the largest, including 90% of ART initiators within the Ministry of Health (66 in total), were eligible for the survey. We used a probability-proportional-to-size design method to sample 25 clinics throughout the country. Consecutive ART-naive patients with HIV about to initiate treatment were invited to participate in the survey; individuals with previous exposure to ART were excluded. We assessed pretreatment HIV-drug resistance by Sanger sequencing and next-generation sequencing of viruses from plasma specimens from eligible participants with Stanford University HIV Drug Resistance Database methods. We obtained follow-up data for a median of 9·4 months (range 6-12) after enrolment. We investigated possible relations between demographic variables and pretreatment drug resistance with univariate and multivariate logistic regression. FINDINGS: Between Feb 3 and July 30, 2015, we screened 288 patients in 25 clinics, from whom 264 provided successfully sequenced viruses with no evidence of current exposure to antiretroviral drugs. With the Sanger method, of these 264 participants, 41 (15·5%, 95% CI 11·4-20·5) had pretreatment resistance to any antiretroviral drug and 28 (10·6%, 7·2-15·0) had pretreatment resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). At least low-level pretreatment resistance (Stanford penalty score ≥15) was noted in 13 (4 ·â€ˆ9%) of participants to efavirenz and in 23 (8·7%) to the combination tenofovir plus emtricitabine plus efavirenz. With next-generation sequencing, of 264 participants, 38 (14·4%, 95% CI 10·4-19·2) had pretreatment resistance to any antiretroviral drug and 26 (9·8%, 6·5-14·1) had pretreatment resistance to NNRTIs. After median follow-up of 8 months (IQR 6·5-9·4, range 5-11) after ART initiation, 97 (72%) of 135 NNRTI initiators achieved viral suppression (<50 copies per mL) compared with ten (40%) of 25 individuals who started with protease inhibitor-based regimens (p=0·0045). After multivariate regression considering pretreatment resistance and initial ART regimen as composite variables, people starting NNRTIs with pretreatment drug resistance achieved significantly lower viral suppression (odds ratio 0·24, 95% CI 0·07-0·74; p=0·014) than patients without NNRTI resistance. INTERPRETATION: High levels of pretreatment drug resistance were noted in Mexico, and NNRTI pretreatment drug resistance significantly reduced the effectiveness of first-line ART regimens based on these drugs. Baseline HIV-drug resistance testing for initial ART follow-up and decision making should be considered. FUNDING: The Mexican Government and Consejo Nacional de Ciencia y Tecnología.

Hepatitis C virus infection and non-Hodgkin's lymphoma: a review and case report of nine patient.

The role of hepatitis C virus (HCV) is well established in the development of chronic hepatitis, cirrhosis and hepatic carcinoma, as well as in mixed type II cryoglobulinemia, membranoproliferative glomerulonephritis(MPGN) and porphyria cutanea tarda (PCT). Increasing evidence has been reported of a close association of HCV infection with autoimmune and hematological processes, mainly cytopenias and lymphoproliferative disorders such as B cell non-Hodgkin's lymphoma. We describe the demographic, clinical and histopathological findings of nine patients from the Mexican population with non-Hodgkin's lymphoma and HCV infection.