Identificación del alelo HLA B*57: 01 en una población militar, de Lima-Perú / Identification of the allele HLA B*57: 01 in a military population, from Lima-Peru

El alelo HLA B*57:01 es un marcador genético asociado con la hipersensibilidad al fármaco anti-retroviral abacavir (ABC) y su frecuencia en la población peruana todavía es desconocida. El objetivo fue identificar el alelo HLA B*57:01 en una población militar de Lima, Perú. Se reclutaron 43 personas viviendo con VIH (PVV) quienes aceptaron participar a través de un consentimiento informado. La detección del alelo HLA B*57:01 se realizó mediante RPC en tiempo real (RT-PCR). Asimismo, se determinó la carga viral (CV), el recuento de linfocitos CD4 y la genotipificación del VIH. Se identificaron dos casos positivos al alelo HLA B*57:01 (4,7%). Además, uno de ellos presentó múltiples mutaciones de resistencia a los anti-retrovirales (ARV), incluyendo ABC. Se demostró por primera vez en el Perú la presencia del alelo HLA B*57:01.

The HLA B*57:01 allele is a genetic marker associated with hypersensitivity to the antiretroviral Abacavir (ABC) and its frequency in the Peruvian population is still unknown. The objective was to identify the HLA B*57:01 allele in a military population from Lima, Peru. Forty three people living with HIV (PLWH) were recruited, who agreed to participate through informed consent. Detection of the HLA B*57:01 allele was performed by real-time PCR (RT-PCR). Likewise, viral load (VL), CD4 lymphocyte count and HIV genotyping were determined. Two cases positive for the HLA B*57:01 allele (4.7%) were identified. In addition, one of them had multiple resistance mutations to antiretrovirals (ARVs), including ABC. The presence of the HLA B*57:01 allele was demonstrated for the first time in Peru.

Clinical outcomes and risk factors for immune recovery and all-cause mortality in Latin Americans living with HIV with virological success: a retrospective cohort study.

INTRODUCTION: Immune reconstitution following antiretroviral therapy (ART) initiation is crucial to prevent AIDS and non-AIDS-related comorbidities. Patients with suppressed viraemia who fail to restore cellular immunity are exposed to an increased risk of morbidity and mortality during long-term follow-up, although the underlying mechanisms remain poorly understood. We aim to describe clinical outcomes and factors associated with the worse immune recovery and all-cause mortality in people living with HIV (PLWH) from Latin America following ART initiation. METHODS: Retrospective cohort study using the CCASAnet database: PLWH ≥18 years of age at ART initiation using a three drug-based combination therapy and with medical follow-up for ≥24 months after ART initiation and undetectable viral load were included. Patients were divided into four immune recovery groups based on rounded quartiles of increase in CD4 T-cell count at 2 years of treatment (<150, [150, 250), [250, 350] and >350 cells/mm3 ). Primary outcomes included all-cause mortality, AIDS-defining events and non-communicable diseases that occurred >2 years after ART initiation. Factors associated with an increase in CD4 T-cell count at 2 years of treatment were evaluated using a cumulative probability model with a logit link. RESULTS: In our cohort of 4496 Latin American PLWH, we found that patients with the lowest CD4 increase (<150) had the lowest survival probability at 10 years of follow-up. Lower increase in CD4 count following therapy initiation (and remarkably not a lower baseline CD4 T-cell count) and older age were risk factors for all-cause mortality. We also found that older age, male sex and higher baseline CD4 T-cell count were associated with lower CD4 count increase following therapy initiation. CONCLUSIONS: Our study shows that PLWH with lower increases in CD4 count have lower survival probabilities. CD4 increase during follow-up might be a better predictor of mortality in undetectable PLWH than baseline CD4 count. Therefore, it should be included as a routine clinical variable to assess immune recovery and overall survival.

Variations in CD4 counts during pregnancy in women living with HIV.

OBJECTIVE: Our objective was to determine the frequency at which CD4 counts drop below 200 cells/mm3 during pregnancy in women living with HIV and to identify factors associated with this. METHODS: Data from 2005 to 2020 from two prospective Canadian cohorts of pregnant women living with HIV were extracted. As per national guidelines, women received antiretroviral therapy and CD4 counts were monitored once per trimester and at delivery. RESULTS: Among 775 included cases, 72 (9.3%) had CD4 counts <200 cells/mm3 at the first pregnancy visit. Of the 703 remaining pregnancies with CD4 counts ≥200 cells/mm3 at the initial visit, 20 (2.8%) were associated with a drop to <200 cells/mm3 . In univariate analysis, factors associated with this drop were coinfection with hepatitis B virus or hepatitis C virus (odds ratio [OR] 4.0, 95% confidence interval [CI] 1.52-10.50), lower first visit CD4 counts (OR 0.165, 95% CI 0.08-0.34), and baseline haemoglobin levels <11 g/dL (OR 2.89, 95% CI 1.04-8.00). In multivariable analysis, only CD4 count at first visit remained independently associated with this drop. A cut-off CD4 count ≤450 cells/mm3 at the first pregnancy visit had a sensitivity of 100% to detect cases of CD4 drop to <200 cells/mm3 . CONCLUSION: A drop of CD4 count to <200 cells/mm3 is uncommon during pregnancy in women living with HIV. Our results suggest that CD4 monitoring only once in pregnancy would be safe in women whose CD4 count is >450 cells/mm3 at the first pregnancy visit.

Nutrition counselling and clinical outcomes in HIV: A systematic review and meta-analysis.

BACKGROUND: People living with the HIV (PLHIV) are at an increased risk of various diseases due to a weakened immune system, particularly if they are naïve or poorly adherent to antiretroviral therapy (ART). Nutrients play a critical role in improving immune health, especially among this population. We systematically reviewed the evidence concerning the impact of nutritional counselling on the occurrence of important clinical outcomes among PLHIV. METHODS: Medical literature databases (PubMed, EMBASE and Web of Science) were searched from inception to October 2022 for relevant published studies (n = 12) of nutritional counselling and HIV-related outcomes in adults on ART. Random-effects meta-analyses were conducted when the exposure-outcome relationships were similar in three or more studies. RESULTS: Although the methodologies of nutritional intervention varied across all studies, overall, the evidence from the meta-analysis indicates a nsignificant positive association between nutrition counselling and improvements in CD4 cell count, body mass index and low-density lipoprotein concentration. However, the existing literature does not provide enough evidence to establish a significant impact of nutrition counselling on other immune, anthropometric, and metabolic outcomes including viral load, weight, and lean mass due to the differences in the study designs. CONCLUSION: Well-powered randomized controlled trials are needed that explore the effect of evidence-based, individualized nutrition counselling on HIV-related clinical outcomes.

Evaluación comparativa de medición de linfocitos CD4+ por dos técnicas: estándar nacional versus test rápido de ejecución local / Comparative evaluation of CD4+ lymphocyte measurement by two techniques: national standard versus point-of-care rapid test

ANTECEDENTES: El recuento de linfocitos CD4+ (LTCD4) es una herramienta fundamental para la evaluación y seguimiento de los pacientes que viven con VIH. En Chile, la medición de LTCD4 estandarizada es por citometría de flujo. En el sistema público se realiza en forma centralizada en tres centros. Actualmente existen tecnologías de medición rápida de recuento de LTCD4 en el lugar de atención, permitiendo optimizar la atención de pacientes con infección por VIH. OBJETIVO: Comparar la precisión de un test rápido de ejecución local versus la técnica estándar. METODOLOGÍA: Realización de ambas técnicas en un grupo de 102 pacientes durante su control regular de salud. RESULTADOS: El rango de variación promedio de los resultados entre las dos técnicas fue de 10%, con una concordancia en los recuentos de LTCD4 de 97% para el rango de CD4 < 200 cél/uL, de 88% para los pacientes con recuento de LTCD4 entre 200 y 349 cél/uL y de 67% en los rangos superiores. CONCLUSIÓN: La técnica por test rápido es un sistema fácil de aplicar, de bajo costo, con alta concordancia con la técnica estándar, lo que debería considerarse en la atención de los pacientes que viven con VIH.

BACKGROUND: The CD4+ lymphocyte cell count is an instrumental tool for the assessment and follow-up in the therapeutic management of patients living with HIV. In Chile, the standardized CD4+ lymphocyte count technique is by flow cytometry. In the public health system, it is performed centralized in 3 sites. Currently, there are technologies that allow measuring the CD4 lymphocyte count at the point of care, allowing to optimize the care of HIV-infected patients. AIM: To compare the accuracy of a point of care rapid test versus the standard technique in patients under regular care at a single HIV center. RESULTS: The average variation of the results between the two techniques was 10%, with a 97% concordance in CD4 range values for patients with CD4 below 200 cells/uL, 88% for CD4 counts between 200 and 349 cells/uL. and 67% above that range. CONCLUSION: This point of care test is an easy-to-operate, low-cost system with high correlation with the standard technique and should be considered in the care of patients living with HIV.

Dietary pattern association with CD4 cells count in patients living with human immunodeficiency virus: A cross-sectional study.

Background: Considering contradictory reports about the impact of dietary pattern on CD4 cell count in previous studies and the potential importance of diet on the immune system, this study aimed to assess the association between dietary patterns and CD4 count among HIV-infected patients. Methods: This cross-sectional study was conducted among HIV-infected patients aged 18-60 who registered in the referral Voluntary Counseling and Testing Center of Shiraz, Iran. The principal component analysis identified nutritional patterns and factors. The association between the score of the dietary patterns and CD4 count was considered in two categories of CD4 more/less than 500 and using backward logistic regression after adjusting for confounders. Results: A total of 226 participants were included in the analysis. CD4 was significantly lower in males (p < 0.001). Participants with illegal drug use (p < 0.001), HCV (p = 0.001), and HBV (p < 0.001) had lower serum CD4. Four extracted dietary patterns were a Plant-rich diet, Healthy animal-based proteins, a Western diet, and Affordable calorie and protein patterns. There was an association between CD4 and Western diet patterns in the best model in which age, gender, weight, and HBV were included. Each unit increase in Western diet score increased the odds of CD4 less than 500 by 57% (OR = 1.57; CI 95% 1.06-2.34, p = 0.02). Conclusion: Among the four dietary patterns, the Western diet comprising a high intake of refined sugar and grain, saturated and trans fats, and animal protein sources, especially high-fat red meat, had a statistically significant relationship with a decrease in CD4 cell count.

Variable Outcomes of Hepatitis E Infections in Patients with Hemato-Oncologic Diseases.

INTRODUCTION: The hepatitis E virus (HEV) represents an important cause of viral hepatitis and could cause chronic infections in immunocompromised patients. However, data about immunocompromised patients other than solid organ transplant recipients are limited. METHODS: We identified patients from a laboratory database and retrospectively compiled and analyzed clinical as well as laboratory data in detail. RESULTS: Overall, 22 severely immunosuppressed patients, excluding solid organ transplant recipients, were identified. Four patients did not experience viral clearance (one without and three despite ribavirin therapy). Three patients acquired the infection after allogeneic hematopoietic stem cell transplantation (alloHSCT) and recovered spontaneously, whereas another patient, infected prior to alloHSCT, developed a chronic infection. Four patients failed to clear HEV, resulting in fatal liver failure in 2 patients. The CD4+ cell counts increased in all but 1 patient attaining a sustained virological response (SVR), as compared to patients with clinical failure. Severe immunoglobulin deficiency did not appear to obviate the control of HEV. Six of ten (60%) patients with and nine of 12 (75%) patients without ribavirin therapy achieved an SVR. CONCLUSIONS: Upfront ribavirin therapy does not appear mandatory in patients without CD4+ lymphopenia, but a prolonged HEV replication carries the risk of liver failure. Our data suggest that chronic HEV infections could cause T-cell exhaustion, which might be overruled with ribavirin therapy.

Recuento de linfocitos CD4, carga viral y colonización oral por Candida en personas viviendo con VIH/SIDA

Objetivos: determinar la correlación entre el recuento de CD4, carga viral y la colonización oral por Candida en personas viviendo con VIH/SIDA (PVVS) que reciben terapia antirretroviral (TAR). Métodos: se realizó un estudio transversal correlacional con 35 participantes que recibían tratamiento antirretroviral. Mediante citometría de flujo se determinó el recuento de CD4; la carga viral se determinó mediante RT-PCRq y la confirmación de colonización oral se realizó mediante aislamiento de Candida spp. Resultados: el recuento de CD4 se correlacionó significativamente de manera inversa con la carga viral (rho de Spearman = -0,457, p=0,006; Kendall Tau-b= -0,306, p=0,012) y con la colonización oral por Candida (rho de Spearman = -0,442, p=0,008; Kendall Tau-b= -0,366, p=0,010), no se encontró significancia estadística entre la carga viral y colonización (p>0,05). Conclusiones: En las PVVS que reciben TAR, los recuentos bajos de CD4 se relacionan con mayor colonización oral por Candida, no se encontró asociación de dicha colonización con la carga viral.

Objectives: to determine the correlation between CD4 count, viral load, and oral Candida colonization in people living with HIV/AIDS (PLWHA) receiving antiretroviral therapy (ART). Methods: a correlational cross-sectional study was conducted with 35 participants receiving antiretroviral treatment. Using flow cytometry, the CD4 count was determined; the viral load was determined by RT-PCRq and confirmation of oral colonization was made by isolating Candida spp. Results: CD4 count was significantly inversely correlated with viral load (Spearman's rho = -0.457, p=0.006; Kendall Tau-b= -0.306, p=0.012) and with oral Candida colonization (Spearman's rho = -0.442, p=0.008; Kendall Tau-b= -0.366, p=0,010), no statistical significance was found between viral load and colonization (p>0.05). Conclusions: in PLWHA receiving ART, low CD4 counts are associated with greater oral colonization by Candida; no association of said colonization with viral load was found.

The association of CD4 lymphocyte count with drug hypersensitivity reaction to highly active antiretroviral therapy, trimethoprim sulfamethoxazole, and antitubercular agents in human immunodeficiency virus patients.

Background: The introduction of highly active antiretroviral therapy (HAART) and antibiotic regimens for the treatment of human immunodeficiency virus (HIV) and its concomitant opportunistic infections, respectively, significantly improve the morbidity and mortality of the infected patients. However, these drugs commonly cause drug hypersensitivity reactions (DHRs) in patients with acquired immunodeficiency syndrome. The reason proposed are multifactorial, which includes immune hyperactivation, changes in drug metabolism, patient cytokine profiles, oxidative stress, genetic predisposition, and the principal target in HIV patients, the CD4+ lymphocytes. Objective: This study determined the association of CD4 count and DHRs to first-line HAART, trimethoprim sulfamethoxazole, and antitubercular agents among HIV patients. Methods: This is a retrospective analytical study. Review of charts were done. The demographic and clinical profile used a descriptive statistics such as mean and standard deviation for quantitative data and frequency and percent for categorical data. Chi-square and Fisher exact tests were used to measure the degree of the relationship of CD4 count and DHRs. Results: A total of 337 eligible patients were included. There was a 25% incidence of hypersensitivity reactions. However, the prevalence of DHRs across the different CD4 groups was not statistically significant (p = 0.167). Likewise, the study found no significant association between the CD4 count and DHRs to first-line HAART, trimethoprim sulfamethoxazole, and antitubercular agents (p = 0.311). The most common DHR was morbilliform rash, and nevirapine was the most reported antiretroviral drug causing DHR. Conclusion: There was no association in the CD4 count and DHRs to first-line HAART, trimethoprim sulfamethoxazole, and antitubercular agents. Hence, regardless of the baseline CD4 lymphocyte count, the physician should be vigilant in monitoring hypersensitivity reactions. Patient education on common DHRs is very important upon diagnosis of HIV and/or initiation of treatment.

A curious case of gingival enlargement - From seropositive diagnosis for human immunodeficiency virus to periodontal management.

Gingival enlargement may be a result of multifactorial etiology which includes local factors such as calculus, food lodgement, overhanging restorations, and overextended dentures as well as systemic conditions such as hormonal disturbances and blood dyscrasias. Acquired immune deficiency is a manifestation of immune disorder caused by a retrovirus Human Immunodeficiency Virus (HIV). The association of Acquired Immunodeficiency Syndrome or HIV with oral and periodontal lesions is highly significant. Seropositive patients usually present with periodontal diseases and atypical periodontal lesions. These clinical findings may prove to be a link for probing patients' systemic health. This case report describes one such case of a patient, unaware of HIV infection with localized gingival overgrowth, wherein detailed probing and investigation led to the diagnosis of underlying systemic condition as acquired immunodeficiency. Subsequently, antiretroviral therapy was started, and nonsurgical periodontal therapy was performed to resolve the gingival overgrowth.

Association between frailty phenotype, quantification of plasma HIV-1 RNA, CD4 cell count and HAART in HIV-positive subjects: a systematic review and meta-analysis of observational studies.

HIV infection causes a constant activation of the immune system and contributes to an enhanced systemic pro-inflammatory cytokine milieu, which has been associated with premature aging and frailty. We performed a systematic review and meta-analysis to analyze whether the HIV-1 RNA load, CD4+ T-lymphocyte counts and exposure to HAART in HIV-positive subjects are associated with frailty phenotype. Searches were performed in PubMed, SCOPUS, Lilacs, Web of Science, Google Scholar, and OpenThesis databases. We used the odds ratio as a measure of the association. We used either a fixed or random-effects model to pool the results of individual studies depending on the presence of heterogeneity. Eleven studies were included in the review. Data from 8035 HIV-positive subjects were analyzed; 2413 of the subjects had viral load detectable, 981 had a CD4T-cell count <350 cells/µL, and 1342 had HAART exposure information. We found an association between frailty and CD4T-cell count <350 cells/µL (OR 2.68, CI 95% 1.68-4.26, I2 = 46%), HIV-1 RNA load detectable (OR 1.71, CI 95% 1.38-2.12, I2 = 0%), and protease inhibitor-containing HAART regimen (OR 2.21, CI 95% 1.26-3.89, I2 = 0%). Further studies are necessary to evaluate the effects of other factors on the development of clinical features related to frailty.

[Ocular manifestations associated to CD4+ in patients with human immunodeficiency virus]. / Manifestaciones oculares asociadas a CD4+ en pacientes con virus de inmunodeficiencia humana.

BACKGROUND: Since the first cases of human immunodeficiency virus (HIV), ocular manifestations secondary to infection have been known and these have been related to the CD4+ lymphocyte count. OBJECTIVE: To describe the correlation between ocular manifestations in patients with HIV and the CD4+ lymphocyte count. MATERIAL AND METHODS: Analytical cross-sectional study of patients with HIV whose CD4+ count was correlated with the presence of ophthalmological manifestations. RESULTS: 21 patients between 26 and 67 years were studied. Only 3 patients were not on antiretroviral therapy. 67% of the patients presented some type of ocular manifestation, 42% presented non-infection related manifestations, 47% related manifestations and 24% both. Conjunctival microangiopathy was the most frequent ocular manifestation (35.7%). There was a statistically significant correlation (r = 0.76, p = 0.0001) between eye manifestations related to infection and CD4+ lymphocyte count. CONCLUSIONS: Patients with HIV frequently present ocular manifestations, the majority related to infection; there is a correlation between the presence of these with the CD4+ count. However, a similar number of manifestations not related to infection occurred without correlation with the count; therefore, HIV patients should have periodic ophthalmological examinations, independently of CD4+ count.

INTRODUCCIÓN: desde los primeros casos de virus de inmunodeficiencia humana (VIH), se conocen manifestaciones oculares secundarias a la infección y estas se han relacionado con el conteo de linfocitos CD4+. OBJETIVO: describir la correlación entre las manifestaciones oculares en pacientes con VIH y el conteo de linfocitos CD4+. MATERIAL Y MÉTODOS: estudio transversal analítico de pacientes con VIH, en quienes se analizó la correlación entre conteo de CD4+ y manifestaciones oftalmológicas. RESULTADOS: se incluyeron 21 pacientes entre 26 y 67 años de edad. Solo tres no se encontraban en terapia antirretroviral. El 67% presentó algún tipo de manifestación ocular, 42% presentó manifestaciones no relacionadas con la infección, 47% manifestaciones relacionadas y 24% ambas. La microangiopatía de la conjuntiva fue la manifestación ocular más frecuente (35.7%). Hubo una correlación estadísticamente significativa (r = 0.76, p = 0.0001) entre las manifestaciones oculares relacionadas con la infección y el conteo de linfocitos CD4+. CONCLUSIONES: los pacientes con VIH presentan con frecuencia manifestaciones oculares, la mayoría asociadas a la infección. Existe correlación entre la presencia de estas con el conteo de CD4+; sin embargo, un número similar de manifestaciones no asociadas a la infección se presentaron sin correlación con el conteo, por lo que los pacientes con VIH deberían tener revisiones oftalmológicas periódicas, independientemente del conteo de CD4+.

Spectrum of malignancies among human immunodeficiency virus-infected patients at a tertiary level human immunodeficiency virus-anti-retroviral therapy center in a North Indian hospital.

INTRODUCTION: Human immunodeficiency virus (HIV)-infected individuals have a higher risk of some types of cancer. A chronic immunodeficiency state, increased survival in the highly active antiretroviral therapy (HAART) era and predisposition to certain oncogenic viral infections have been postulated as the main reasons. While, the incidence of acquired immunodeficiency syndrome (AIDS) defining cancers (ADCs) is declining in the post-HAART era, non-AIDS-defining cancers (NADCs) are becoming an important cause of mortality in these patients. MATERIALS AND METHODS: Analysis of the data of HIV-infected patients registered at an apex centre was done for 7 years. All patients were subjected to routine investigations on presentation (baseline) and during follow-up for the occurrence of any malignant disease. CD4 cell counts before starting anti-retroviral therapy and before the diagnosis of malignancy were noted. The date of the last review and the current status/outcome were recorded. RESULTS: Out of 1258, 17 patients were diagnosed with various malignancies. Seven patients (41.2%) had ADCs and the remaining 10 (58.8%) had NADCs. The mean duration between diagnosis of HIV infection and diagnosis of malignancy was 59.53 months. The mean survival duration from the diagnosis of malignancy for all cases was 21 months. The mean survival duration was 29 months and 15 months for ADC and NADC group respectively. CONCLUSIONS: NADCs are on the rise in the era of effective use of HAART and increasing life span of HIV patients. The index of suspicion for cancer should be higher in such patients, especially compared to opportunistic infections in view of good immunovirologic status.

Supervivencia en las personas que viven con VIH en el marco del sistema de salud colombiano 2011-2018 / Survival in people living with HIV in the framework the Colombian health system: 2011-2018

Resumen Objetivo: Describir la supervivencia a siete años y los principales factores asociados a esta, en las personas con VIH que fueron atendidas en el sistema de salud colombiano entre 2011 a 2018. Métodos: Análisis de supervivencia de una cohorte de 64 039 personas diagnosticadas con VIH en Colombia. Se aplicó el método de Kaplan-Meier para estimar la probabilidad de supervivencia a partir de la fecha del diagnóstico. Se ajustó un modelo de supervivencia paramétrico flexible de Royston Parmar. Resultados: La estimación de la supervivencia global a 7 años fue de 94,8% (IC 95%: 94,5-95,2). El mayor riesgo de muerte se presentó en los hombres (HR: 1,2; IC 95%: 1,1-1,4; p: 0,010); en personas ≥50 años de edad (HR: 3,1; IC 95%: 1,6-6,3; p: 0,002); en el régimen subsidiado (HR: 2,2; IC 95%: 1,9-2,5; p: <0,001); en la etapa sida (HR: 2,8; IC 95%: 2,1-3,7; p: <0,001); en quienes presentaron la última carga viral detectable (HR: 7,1; IC 95%: 6,0-8,3; p: <0,001); y en quienes mostraron conteo de linfocitos T CD4+ <350 células/μL (HR: 1,9; IC 95%: 1,4-2,4; p: <0,001). Conclusión: La probabilidad de la supervivencia de las personas que viven con VIH aumenta al ser diagnosticados en edades jóvenes, en quienes presenten un recuento de linfocitos T CD4+ ≥350 células/μL, una carga viral indetectable (< 50 copias/mL) y no se encuentren en etapa sida.

Summary Objective: to describe the seven-year survival and predictors of mortality among people with HIV who were treated in the Colombian health system between 2011 and 2018. Methods: 64 039 people diagnosed with HIV in Colombia were included. Kaplan-Meier analysis estimated the probability of survival from the date of diagnosis. A Royston Parmar flexible parametric survival model was fitted. Results: The overall survival at 7 years was 94.8% (95% CI: 94.5-95.2). Survival was related to sex (men, HR: 1.2; 95% CI: 1.1-1.4; p: 0.010); people ≥50 years of age (HR: 3.1; 95% CI: 1.6-6.3; p: 0.002); subsidized regime (HR: 2.2; 95% CI: 1.9-2.5; p: <0.001); AIDS stage (HR: 2.8; 95% CI: 2.1-3.7; p: <0.001); a detectable viral load (HR: 7.1; 95% CI: 6.0-8.3; p: <0.001); and a CD4+ Lymphocyte count <350 cells/μL (HR: 1.9; 95% CI: 1.4-2.4; p: <0.001). Conclusion: The probability of survival of people living with HIV increases when they are diagnosed at a young age, in those with a CD4+ T Lymphocyte count ≥350 cells/μL, an undetectable viral load (<50 copies/mL) and are not in the AIDS stage.

Suspected Central Nervous System Infections in HIV-Infected Adults.

Objectives: To study the differential diagnosis of HIV-infected patients with suspected central nervous system (CNS) infections and the association of CD4 counts with the final diagnosis. Methods: We analyzed HIV-infected patients from a prospective cohort study on the diagnostic accuracy of clinical and laboratory characteristics in adults with suspected CNS infections in an academic hospital in Amsterdam, the Netherlands, who underwent cerebrospinal fluid (CSF) examination. Results: Thirty-four (9.4%) out of 363 patients with suspected CNS infections were HIV-positive of whom 18 (53%) were diagnosed to have CNS infection, with median CD4 counts of 255 cells/µl. The spectrum of CNS infections consisted of progressive multifocal leukoencephalopathy in three patients (17%); cryptococcal meningoencephalitis, toxoplasma encephalitis, angiostrongylus eosinophilic meningitis, and HIV encephalitis each in two (11%); and cytomegalovirus encephalitis, neurosyphilis, tuberculous meningoencephalitis, histoplasma encephalitis, and varicella-zoster virus meningitis each in one (6%). Clinical characteristics and blood parameters did not differ between HIV-infected patients with CNS infections and other diagnoses. The best predictor for CNS infections was the CSF leukocyte count (AUC = 0.77, 95 CI% 0.61-0.94). The diagnosis of CNS infection was not associated with the CD4 count (median 205 vs. 370, p = 0.21). Two patients (11%) with CNS infections died and two (11%) had neurological sequelae. Conclusions: Half of the patients with suspected CNS infections are diagnosed with a CNS infection, and this was not related to CD4 counts. The best predictor for CNS infections was the CSF leukocyte count.

Manifestaciones oculares asociadas a CD4+ en pacientes con virus de inmunodeficiencia humana / Ocular manifestations associated to CD4+ in patients with human immunodeficiency virus

Introducción: desde los primeros casos de virus de inmunodeficiencia humana (VIH), se conocen manifestaciones oculares secundarias a la infección y estas se han relacionado con el conteo de linfocitos CD4+. Objetivo: describir la correlación entre las manifestaciones oculares en pacientes con VIH y el conteo de linfocitos CD4+. Material y métodos: estudio transversal analítico de pacientes con VIH, en quienes se analizó la correlación entre conteo de CD4+ y manifestaciones oftalmológicas. Resultados: se incluyeron 21 pacientes entre 26 y 67 años de edad. Solo tres no se encontraban en terapia antirretroviral. El 67% presentó algún tipo de manifestación ocular, 42% presentó manifestaciones no relacionadas con la infección, 47% manifestaciones relacionadas y 24% ambas. La microangiopatía de la conjuntiva fue la manifestación ocular más frecuente (35.7%). Hubo una correlación estadísticamente significativa (r = 0.76, p = 0.0001) entre las manifestaciones oculares relacionadas con la infección y el conteo de linfocitos CD4+. Conclusiones: los pacientes con VIH presentan con frecuencia manifestaciones oculares, la mayoría asociadas a la infección. Existe correlación entre la presencia de estas con el conteo de CD4+; sin embargo, un número similar de manifestaciones no asociadas a la infección se presentaron sin correlación con el conteo, por lo que los pacientes con VIH deberían tener revisiones oftalmológicas periódicas, independientemente del conteo de CD4+.

Background: Since the first cases of human immunodeficiency virus (HIV), ocular manifestations secondary to infection have been known and these have been related to the CD4+ lymphocyte count. Objective: To describe the correlation between ocular manifestations in patients with HIV and the CD4+ lymphocyte count. Material and methods: Analytical cross-sectional study of patients with HIV whose CD4+ count was correlated with the presence of ophthalmological manifestations. Results: 21 patients between 26 and 67 years were studied. Only 3 patients were not on antiretroviral therapy. 67% of the patients presented some type of ocular manifestation, 42% presented non-infection related manifestations, 47% related manifestations and 24% both. Conjunctival microangiopathy was the most frequent ocular manifestation (35.7%). There was a statistically significant correlation (r = 0.76, p = 0.0001) between eye manifestations related to infection and CD4+ lymphocyte count. Conclusions: Patients with HIV frequently present ocular manifestations, the majority related to infection; there is a correlation between the presence of these with the CD4+ count. However, a similar number of manifestations not related to infection occurred without correlation with the count; therefore, HIV patients should have periodic ophthalmological examinations, independently of CD4+ count.

Regression discontinuity analysis demonstrated varied effect of Treat-All on CD4 testing among Southern African countries.

OBJECTIVE: To determine whether Treat-All policy impacted laboratory testing practices of antiretroviral therapy (ART) programs in Southern Africa. STUDY DESIGN AND SETTING: We used HIV cohort data from Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in a regression discontinuity design to estimate changes in pre-ART CD4 testing and viral load monitoring following national Treat-all adoption that occurred during 2016 to 2017. This study included more than 230,000 ART-naïve people living with HIV (PLHIV) aged five years or older who started ART within two years of national Treat-All adoption. RESULTS: We found pre-ART CD4 testing decreased following adoption of Treat-All recommendations in Malawi (-21.4 percentage points (pp), 95% confidence interval, CI: -26.8, -16.0) and in Mozambique (-8.8pp, 95% CI: -14.9, -2.8), but increased in Zambia (+2.7pp, 95% CI: +0.4, +5.1). Treat-All policy had no effect on viral load monitoring, except among females in South Africa (+7.1pp, 95% CI: +1.1, +13.0). CONCLUSION: Treat-All policy expanded ART eligibility, but led to reductions in pre-ART CD4 testing in some countries that may weaken advanced HIV disease management. Continued and expanded support of CD4 and viral load laboratory capacity is needed to further improve treatment successes and allow for uniform evaluation of ART implementation across Southern Africa.

Current and Past Immunodeficiency Are Associated With Higher Hospitalization Rates Among Persons on Virologically Suppressive Antiretroviral Therapy for up to 11 Years.

BACKGROUND: Persons with human immunodeficiency virus (PWH) with persistently low CD4 counts despite efficacious antiretroviral therapy could have higher hospitalization risk. METHODS: In 6 US and Canadian clinical cohorts, PWH with virologic suppression for ≥1 year in 2005-2015 were followed until virologic failure, loss to follow-up, death, or study end. Stratified by early (years 2-5) and long-term (years 6-11) suppression and lowest presuppression CD4 count <200 and ≥200 cells/µL, Poisson regression models estimated hospitalization incidence rate ratios (aIRRs) comparing patients by time-updated CD4 count category, adjusted for cohort, age, gender, calendar year, suppression duration, and lowest presuppression CD4 count. RESULTS: The 6997 included patients (19 980 person-years) were 81% cisgender men and 40% white. Among patients with lowest presuppression CD4 count <200 cells/µL (44%), patients with current CD4 count 200-350 vs >500 cells/µL had aIRRs of 1.44 during early suppression (95% confidence interval [CI], 1.01-2.06), and 1.67 (95% CI, 1.03-2.72) during long-term suppression. Among patients with lowest presuppression CD4 count ≥200 (56%), patients with current CD4 351-500 vs >500 cells/µL had an aIRR of 1.22 (95% CI, .93-1.60) during early suppression and 2.09 (95% CI, 1.18-3.70) during long-term suppression. CONCLUSIONS: Virologically suppressed patients with lower CD4 counts experienced higher hospitalization rates and could potentially benefit from targeted clinical management strategies.

Factors related to baseline CD4 cell counts in HIV/AIDS patients: comparison of poisson, generalized poisson and negative binomial regression models.

OBJECTIVE: CD4 Lymphocyte Count (CD4) is a major predictor of HIV progression to AIDS. Exploring the factors affecting CD4 levels may assist healthcare staff and patients in management and monitoring of health cares. This retrospective cohort study aimed to explore factors associated with CD4 cell counts at the time of diagnosis in HIV patients using Poisson, Generalized Poisson, and Negative Binomial regression models. RESULTS: Out of 4402 HIV patients diagnosis in Iran from 1987 to 2016, 3030 (68.8%) were males, and the mean age was 34.8 ± 10.4 years. The results indicate that the Negative Binomial model outperformed the other models in terms of AIC, log-likelihood and RMSE criteria. In this model, factors include sex, age, clinical stage and Tuberculosis (TB) co-infection were significantly associated with CD4 count (P < 0.05). CONCLUSION: Given the effect of age, sex, clinical stage and stage of HIV on CD4 count of the patients, adopting policies and strategies to increase awareness and encourage people to seek early HIV testing and care is advantageous.

Urine Lipoarabinomannan Testing for All HIV Patients Hospitalized in Medical Wards Identifies a Large Proportion of Patients With Tuberculosis at Risk of Death.

BACKGROUND: Diagnosing tuberculosis (TB), the leading cause of death in people with HIV, remains a challenge in resource-limited countries. We assessed TB diagnosis using a strategy that included systematic urine lipoarabinomannan (LAM) testing for all HIV patients hospitalized in medical wards and 6-month mortality according to LAM results. METHODS: This prospective, observational study included adult HIV patients hospitalized in the medical wards of a public district hospital in Malawi regardless of their TB symptoms or CD4 count. Each patient had a clinical examination, and Alere Determine TB-LAM, sputum microscopy, sputum GeneXpert MTB/RIF (Xpert), chest x-ray, and CD4 count were systematically requested. RESULTS: Among 387 inpatients, 54% had a CD4 <200 cells/µL, 64% had presumptive TB, and 90% had ≥1 TB symptom recorded in their medical file. LAM results were available for 99.0% of patients, microscopy for 62.8%, and Xpert for 60.7%. In total, 26.1% (100/383) had LAM-positive results, 48% (48/100) of which were grades 2-4. Any TB laboratory test result was positive in 30.8% (119/387). Among patients with no Xpert result, 28.5% (43/151) were LAM-positive. Cumulative 6-month mortality was 40.1% (151/377): 50.5% (49/97) in LAM-positives and 36.2% (100/276) in LAM-negatives (P = .013). In multivariable regression analyses, LAM-positive patients had a higher risk of mortality than LAM-negatives (adjusted odds ratio, 2.5; 95% CI, 1.1-5.8; P = .037). CONCLUSIONS: In resource-limited hospital medical wards with high TB prevalence, a diagnostic strategy including systematic urine LAM testing for all HIV patients is an easily implementable strategy that identifies a large proportion of patients with TB at risk of death.