HIV Infection Presenting as Haemophagocytic Syndrome

The authors describe a case of a 48-year-old man who presented with four weeks of fever, generalized malaise, weight loss, right upper quadrant abdominal pain and hepatosplenomegaly. He evolved with pancytopenia, bone marrow haemophagocytosis and hyperferritinaemia. Recent diagnosis of HIV infection, with the exclusion of other plausible causes, prompted the diagnosis of haemophagocytic syndrome (HPS) secondary to HIV. Despite intensive care support and initiation of antiretroviral therapy, the patient died. HPS diagnosis secondary to HIV alone demands the exclusion of all the other secondary causes. The best approach includes early diagnosis and specific treatment of the associated cause, whenever possible.

Gastric and Peritoneal Involvement of Human Herpes Virus 8 Related Kaposi Sarcoma in a Patient with Acquired Immunodeficiency Syndrome

Kaposi's sarcoma (KS) is one of the most frequent neoplastic diseases in patients infected with human immunodeficiency virus (HIV). The authors report the case of a 40-year-old male with ascites, peripheral edema and peritoneal carcinomatosis secondary to a gastric KS related to human herpes virus type 8 (HHV-8). The patient had severe immunodeficiency, with a TCD4+ count of 86 cells/µl and newly diagnosed acquired immunodeficiency syndrome. His clinical condition rapidly deteriorated, with multiorgan failure, and he died without the possibility of initiating antiretroviral therapy or chemotherapy. To the authors’ knowledge, carcinomatosis is a rare feature in KS.

Five years retrospective cohort analysis of treatment outcomes of TB-HIV patients at a PEPFAR/DOTS Centre in South Eastern Nigeria.

Background: Human immunodeficiency virus (HIV) associated tuberculosis (TB) remains a major global public health challenge, with an estimated 1.4 million patients worldwide. Co-infection with HIV leads to challenges in the diagnosis and treatment of patients. Objectives: The aim of this study was to assess treatment outcomes of a cohort of smear positive TB-HIV co-infected patients over a five-year study period. Methods: A retrospective cohort study of 600 smear-positive tuberculosis patients registered at the chest unit of the University of Nigeria Teaching Hospital, Enugu from January 2008 to December 2012 was done. The data was analyzed using SPSS Version 17. Results: One hundred and three (17.2%) of the patients were co-infected with TB/HIV, while 398 (66.3%) and 99 (16.5%) were HIV negative and unknown respectively. Among the co-infected patients, 45(43.7%) were cured as against 222(55.8%) in the TBHIV negatives (Z=4.53, p=0.000, 95%CI= 0.12-0.34). Respectively in the TB-HIV co-infected and TB-HIV negative patients, treatment completed were 21(20.4%) and 71(17.8%) (Z=9.15, p=0.000, 95%= 0.4035-0.60); defaulted 19(18.5%) vs 70 (17.6%) (Z=9.29, p=0.000, 95%CI=0.42-0.60), died 10(9.7%) vs. 6(1.5%) (Z=1.22, p=0.224, 95%CI= -0.0286-0.1086), and failures were 1(0.9%) vs. 7(1.8%) (Z=2.48, p=0.013, 95%CI=0.04-0.10). Treatment success rate was lower in TB-HIV co-infected patients, 64.1% compared to TB-HIV negative patients with 73.6%. Also those that defaulted among the TB-HIV co-infected patients (18.5%) were higher than 17.6% among TB-HIV negative patients, a difference of 0.9%. Conclusion: Findings demonstrate that HIV co-infection affects TB treatment outcomes adversely. Treatment adherence, timely and sustained access to antiretroviral therapy for TB/HIV co-infected patients are important.

Reproductive decisions of couples living with HIV in Malawi: What can we learn for future policy and research studies?

Background The rapid scale-up of free antiretroviral therapy has lead to decline in adult mortality at the population level and reduction of vertical transmission. Consequently, some couples living with HIV are maintaining their reproductive decisions; marrying and having children. This paper analyses policies and guidelines on HIV, AIDS and sexual and reproductive health in Malawi for content on marriage and childbearing for couples living with HIV. Methods A qualitative study using interpretive policy analysis approach was conducted from July to December 2010 in two phases. First, data on access to HIV, AIDS and sexual and reproductive health services were collected using in-depth interviews with twenty couples purposively sampled in matrilineal Chiradzulu and patrilineal Chikhwawa communities. Secondly, data were collected from Malawi policies and guidelines on HIV, AIDS and sexual and reproductive health. The documents were reviewed for content on marriage and childbearing for couples living with HIV. Data were analysed using framework approach for applied policy analysis. Results Four categories emerged from each phase. From the study, we extracted health workers attitudes, weak linkage between HIV, AIDS and sexual and reproductive health services, contradictory messages between media and the hospitals and lack of information as factors directly related to guidelines and policies. Analysis of guidelines and policies showed nonprescriptiveness on issues of HIV, AIDS and reproduction: they do not reflect the social cultural experiences of couples living with HIV. In addition, there is; lack of clinical guidelines, external influence on adoption of the policies and guidelines and weak linkages between HIV and AIDS and sexual and reproductive health services. Conclusion This synthesis along with more detailed findings which are reported in other published articles, provide a strong basis for updating the policies and development of easy-to-follow guidelines in order to effectively provide services to couples living with HIV in Malawi.

Causes of cervical lymphadenopathy at Kamuzu Central Hospital

Aim Description of pathologic causes of cervical lymphadenopathy at Kamuzu Central Hospital. Introduction The evaluation of cervical lymphadenopathy is a common diagnostic challenge facing clinicians. Previously at Kamuzu Central Hospital (KCH) tuberculosis (TB) was reported to be the most common cause of cervical lymphadenopathy However, no recent study has assessed this common diagnostic challenge in Malawi, particularly since the beginning of the HIV epidemic and the subsequent scale-up of antiretroviral therapy. Methods We conducted a cross-sectional study of all cervical lymph node specimens from the KCH pathology laboratory between 1 July 2011 and 28 February 2013 and describe patient age, gender, and pathologic diagnoses. Results Our search of the KCH pathology database yielded 179 cases. Of these, 143 (77%) were histologic specimens (open biopsy or core needle samples) while 34 (23%) were cytology specimens. The age range was from 0 to 76 years with a mean of 30 (SD: 19). In adults, the most common diagnosis was malignancy (n=41, 35%), while in children 15 cases each of malignancy and benign masses were diagnosed. Only 6 cases (5%) of TB were diagnosed in adults, and 4 cases (6%) of TB were diagnosed in children. Conclusion Our study shows more malignancy and much less TB than a prior study of cervical lymphadenopathy at KCH. With the successful initiaion of the KCH Pathology Laboratory in 2011, we recommend biopsy or FNA early in the workup of cervical lymphadenopathy to prevent long delays in diagnosis and treatment of curable cancers.

CURB-65 and other markers of illness severity in community-acquired pneumonia among HIV-positive patients

Introduction: As the relative burden of community-acquired bacterial pneumonia among HIV-positive patients increases, adequate prediction of case severity on presentation is crucial. We sought to determine what characteristics measurable on presentation are predictive of worse outcomes. Methods: We studied all admissions for community-acquired bacterial pneumonia over 1 year at a tertiary centre. Patient demographics, comorbidities, HIV-specific markers and CURB-65 scores on Emergency Department presentation were reviewed. Outcomes of interest included mortality, bacteraemia, intensive care unit admission and orotracheal intubation. Results: A total of 396 patients were included, 49 HIV positive and 347 HIV negative. Mean CURB-65 score was 1.3 for HIV-positive and 2.2 for HIV-negative patients (p<0.0001), its predictive value for mortality being maintained in both groups (p¼0.03 and p<0.001, respectively). Adjusting for CURB-65 scores, HIV infection by itself was only associated with bacteraemia (adjusted odds ratio 7.1 CI 95% [2.6–19.5]). Patients with<200 CD4 cells/mL presented similar CURB- 65 adjusted mortality (adjusted odds ratio 1.7 CI 95% [0.2–15.2]), but higher risk of intensive care unit admission (adjusted odds ratio 5.7 CI 95% [1.5–22.0]) and orotracheal intubation (adjusted odds ratio 9.1 CI 95% [2.2–37.1]), compared to HIV-negative patients. These two associations were not observed in the>200 CD4 cells/mL subgroup (adjusted odds ratio 2.2 CI 95% [0.7–7.6] and adjusted odds ratio 0.8 CI 95% [0.1–6.5] respectively). Antiretroviral therapy and viral load suppression were not associated with different outcomes (p>0.05). Conclusions: High CURB-65 scores and CD4 counts<200 cells/mL were both associated with worse outcomes. Severity assessment scales and CD4 counts may both be helpful in predicting severity in HIV-positive patients presenting with community-acquired bacterial pneumonia.

A retrospective observational study of low-level viraemia and its immunological and virological significance: which outcome to expect

This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Sub-epidemics explain localized high prevalence of reduced susceptibility to Rilpivirine in treatment-naive HIV-1-infected patients: subtype and geographic compartmentalization of baseline resistance mutations

This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

Prevalencia y factores de riesgo del síndrome metabólico en pacientes con tratamiento antirretroviral (ARV) que acuden a consulta en el Hospital Vicente Corral Moscoso. Cuenca, 2015

ANTECEDENTES: Desde el año 1987, el impacto y aumento del VIH/SIDA ha llevado a implementar e incrementar combinaciones de Antirretrovirales (ARV), consiguiendo una disminución de la mortalidad en un 35%; sin embargo, nos enfrentamos a otra problemática, la aparición de efectos adversos a largo plazo de estos medicamentos, englobándole al Síndrome Metabólico. OBJETIVO GENERAL: Determinar la prevalencia y factores de riego del Síndrome Metabólico en pacientes que usen Antirretrovirales en el Hospital Vicente Corral Moscoso. METODOLOGÍA: Se realizó un Estudio Analítico - Transversal de prevalencia. Se incluyó a todos los pacientes que pertenecen a la Unidad de Atención Integral para PVVS-HVCM, mayores de 18 años, que reciben tratamiento antirretroviral por más de un mes previa autorización. La información recolectada fue analizada mediante software SPSS 5. RESULTADOS: en una población de 211 pacientes, se encontró una prevalencia del Síndrome Metabólico de 30,3% (n=64) según criterios de IDF. Las variables relacionadas al síndrome metabólico fueron: Edad 42,86 (p 0,000); Sexo femenino 51.6% y masculino 48.4% (p 0,001); IMC: sobrepeso y obesidad 82,8 (p 0,000); Perímetro abdominal 100% (p 0,000); Perfil lipídico: hipertrigliceridemia 86% (p 0,000), hipercolesterolemia 53% (p 0,012), alteración de HDL 83% (p 0,000). CONCLUSIONES: Se encontró una elevada prevalencia de Síndrome Metabólico en pacientes HIV+/SIDA con tratamiento antirretroviral pero no se pudo encontrar relación estadísticamente significativa. Mientras que los factores de riesgo fueron: edad, sexo, IMC, Perímetro Abdominal y dislipidemias

Anomalies immunitaires chez les enfants exposés au VIH mais non infectés.

La thérapie antirétrovirale prévient la transmission mère-enfant du VIH dans plus de 98% des cas lorsqu’administrée pendant la grossesse, le travail et au nouveau-né. L’accessibilité à la thérapie antirétrovirale dans près de 70% des 1,5 millions cas de grossesses VIH+ dans le monde mène à la naissance de plus d’un million d’enfants exposés non infectés chaque année. Le nombre d’enfants exposés non infectés est à la hausse ainsi que les préoccupations concernant leur santé. En effet, plusieurs groupes ont signalé une augmentation de la morbidité et de la mortalité chez les enfants exposés non infectés. L’analyse des données rétrospectives de 705 enfants exposés non infectés de la cohorte mère-enfant du CMIS a révélé qu’à 2 mois d’âge, les enfants nés de mères ayant une charge virale supérieure à 1,000 copies d’ARN / ml avaient une fréquence de lymphocytes B significativement plus élevés par rapport aux enfants exposés non infectés nés de mères ayant une charge virale indétectable. L’objectif de cette étude est de caractériser ces anomalies. Les lymphocytes, provenant du sang de cordon ombilical et de sang veineux obtenu à 6 et 12 mois d’âge, ont été phénotypés par cytométrie en flux à l’aide des marqueurs CD3 / CD10 / CD14 / CD16 / CD19 / CD20 / CD21 / CD27 / IgM pour les lymphocytes B et CD4 / CD8 / CD3 / CCR7 / CD45RA pour les lymphocytes T. De plus, afin d’étudier les capacités fonctionnelles des lymphocytes B CD19+, la réponse antigène-spécifique au vaccin antitétanique a été mesurée par marquage avec des tétramères fluorescents de fragment C du toxoïde tétanique. Nos travaux ont mis en évidence des différences statistiquement significatives entre les enfants exposés non-infectés (ENI) nés de mères avec une charge virale détectable comparativement à ceux nés de mères avec une charge virale indétectable. À la naissance, les enfants ENI nés de mères avec une charge virale détectable avaient significativement moins de lymphocytes B totaux, plus de lymphocytes B mémoires classiques, activés, plasmablastes et lymphocytes T CD8+ mémoires centrales. À 6 mois, ils avaient significativement plus de lymphocytes B naïfs et significativement moins de lymphocytes T CD8+ effecteurs mémoires. À 12 mois d’âge, ils avaient significativement plus de lymphocytes B et T CD8+ totaux; significativement moins de lymphocytes T CD4+ totaux et leurs lymphocytes T affichaient un profil significativement plus activé (plus de cellules mémoires). L’analyse de la réponse antigène-spécifique a révélé une fréquence plus élevé de lymphocytes B mémoires IgM+ suggérant que les enfants nés de mères avec une virémie détectable ont plus de mal à établir une mémoire immunitaire efficace face au vaccin antitétanique. Nos données suggèrent qu’il y a exposition durant le premier trimestre de grossesse à la virémie maternelle et que cette exposition impacte le système immunitaire en développement du fœtus. Les mécanismes sous-jacents causant ces anomalies doivent encore être élucidés et l’épuisement du compartiment T à la naissance et à 6 mois reste à être investigué. Dans un pays industrialisé où l’accès aux soins est facilité, ces anomalies ont des conséquences modérées mais dans des pays à faible et moyen revenu, les conséquences peuvent être beaucoup plus tragiques voir fatales.

Overweight/obesity and HIV disease progression in HIV+ adults in Botswana

Studies indicate that overweight and obesity protect against HIV-disease progression in antiretroviral therapy (ART)-naïve patients. We examined retrospectively the relationship of overweight/obesity with HIV-disease progression in ART-naïve HIV+ adults in Botswana in a case-control study with 18-month follow-up, which included 217 participants, 139 with BMI 18.0-24.9 kg/m 2 and 78 with BMI ≥25 kg/m2. Archived plasma samples were used to determine inflammatory markers: leptin and bacterial endotoxin lipopolysaccharide (LPS), and genotype single nucleotide polymorphisms (SNPs) of the Fat Mass and Obesity Associated Gene (FTO). ^ At baseline, BMI was inversely associated with risk for AIDS-defining conditions (HR=0.218; 95%CI=0.068, 0.701, P=0.011), and higher fat mass was associated with reduced risk of the combined outcome of CD4+cell count ≤250/µL and AIDS-defining conditions, whichever occurred earlier (HR=0.918; 95%CI=0.847, 0.994, P=0.036) over 18 months, adjusting for age, gender, marriage, children, and baseline CD4+cell count and HIV-viral load. ^ FTO-SNP rs17817449 was associated with BMI (OR=1.082; 95%CI=1.001, 1.169; P=0.047). Fat mass was associated with the risk alleles of rs1121980 (OR=1.065; 95%CI=1.009, 1.125, P=0.021), rs8050136 (OR=1.078; 95%CI=1.021, 1.140; P=0.007), and rs17817449 (OR=1.086; 95%CI=1.031, 1.145; P=0.002), controlling for age, gender, tribe, total energy intake, and activity. There were no associations of SNPs with markers of disease progression. ^ Leptin levels were positively associated with BMI (β=1.764; 95%CI=0.788, 2.739; P=0.022) and fat mass (β=0.112; 95%CI=0.090, 0.135; P<0.001), but inversely with viral load (β=-0.305; 95%CI=-0.579, -.031; P=0.030). LPS levels were inversely associated with BMI (OR=0.790, 95%CI=0.630, 0.990; P=0.041), and fat mass (OR=0.852, 95%CI=0.757, 0.958; P=0.007) and directly with viral load (OR=2.608, 95%CI=1.111, 6.124; P=0.028), adjusting for age, gender, smoking and %fat mass. ^ In this cohort, overweight/obesity predicted slower HIV-disease progression. Obesity may confer an advantage in maintaining fat stores to support the overactive immune system. FTO-SNPs may contribute to the variation in fat mass; however, they were not associated with HIV-disease progression. Our findings suggest that the obesity paradox may be explained by the association of increased LPS with lower BMI and higher viral load; while viral load decreased with increasing leptin levels. Studies in African populations are needed to clarify whether genetic variation and inflammation mediate the obesity paradox in HIV-disease progression.^

Anomalies immunitaires chez les enfants exposés au VIH mais non infectés

La thérapie antirétrovirale prévient la transmission mère-enfant du VIH dans plus de 98% des cas lorsqu’administrée pendant la grossesse, le travail et au nouveau-né. L’accessibilité à la thérapie antirétrovirale dans près de 70% des 1,5 millions cas de grossesses VIH+ dans le monde mène à la naissance de plus d’un million d’enfants exposés non infectés chaque année. Le nombre d’enfants exposés non infectés est à la hausse ainsi que les préoccupations concernant leur santé. En effet, plusieurs groupes ont signalé une augmentation de la morbidité et de la mortalité chez les enfants exposés non infectés. L’analyse des données rétrospectives de 705 enfants exposés non infectés de la cohorte mère-enfant du CMIS a révélé qu’à 2 mois d’âge, les enfants nés de mères ayant une charge virale supérieure à 1,000 copies d’ARN / ml avaient une fréquence de lymphocytes B significativement plus élevés par rapport aux enfants exposés non infectés nés de mères ayant une charge virale indétectable. L’objectif de cette étude est de caractériser ces anomalies. Les lymphocytes, provenant du sang de cordon ombilical et de sang veineux obtenu à 6 et 12 mois d’âge, ont été phénotypés par cytométrie en flux à l’aide des marqueurs CD3 / CD10 / CD14 / CD16 / CD19 / CD20 / CD21 / CD27 / IgM pour les lymphocytes B et CD4 / CD8 / CD3 / CCR7 / CD45RA pour les lymphocytes T. De plus, afin d’étudier les capacités fonctionnelles des lymphocytes B CD19+, la réponse antigène-spécifique au vaccin antitétanique a été mesurée par marquage avec des tétramères fluorescents de fragment C du toxoïde tétanique. Nos travaux ont mis en évidence des différences statistiquement significatives entre les enfants exposés non-infectés (ENI) nés de mères avec une charge virale détectable comparativement à ceux nés de mères avec une charge virale indétectable. À la naissance, les enfants ENI nés de mères avec une charge virale détectable avaient significativement moins de lymphocytes B totaux, plus de lymphocytes B mémoires classiques, activés, plasmablastes et lymphocytes T CD8+ mémoires centrales. À 6 mois, ils avaient significativement plus de lymphocytes B naïfs et significativement moins de lymphocytes T CD8+ effecteurs mémoires. À 12 mois d’âge, ils avaient significativement plus de lymphocytes B et T CD8+ totaux; significativement moins de lymphocytes T CD4+ totaux et leurs lymphocytes T affichaient un profil significativement plus activé (plus de cellules mémoires). L’analyse de la réponse antigène-spécifique a révélé une fréquence plus élevé de lymphocytes B mémoires IgM+ suggérant que les enfants nés de mères avec une virémie détectable ont plus de mal à établir une mémoire immunitaire efficace face au vaccin antitétanique. Nos données suggèrent qu’il y a exposition durant le premier trimestre de grossesse à la virémie maternelle et que cette exposition impacte le système immunitaire en développement du fœtus. Les mécanismes sous-jacents causant ces anomalies doivent encore être élucidés et l’épuisement du compartiment T à la naissance et à 6 mois reste à être investigué. Dans un pays industrialisé où l’accès aux soins est facilité, ces anomalies ont des conséquences modérées mais dans des pays à faible et moyen revenu, les conséquences peuvent être beaucoup plus tragiques voir fatales.

Assessment of cytokine values in serum by RT-PCR in HIV-1 infected individuals with and without highly active anti-retroviral therapy (HAART)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Spinal cord injury therapy through active learning

Therapy employing epidural electrostimulation holds great potential for improving therapy for patients with spinal cord injury (SCI) (Harkema et al., 2011). Further promising results from combined therapies using electrostimulation have also been recently obtained (e.g., van den Brand et al., 2012). The devices being developed to deliver the stimulation are highly flexible, capable of delivering any individual stimulus among a combinatorially large set of stimuli (Gad et al., 2013). While this extreme flexibility is very useful for ensuring that the device can deliver an appropriate stimulus, the challenge of choosing good stimuli is quite substantial, even for expert human experimenters. To develop a fully implantable, autonomous device which can provide useful therapy, it is necessary to design an algorithmic method for choosing the stimulus parameters. Such a method can be used in a clinical setting, by caregivers who are not experts in the neurostimulator's use, and to allow the system to adapt autonomously between visits to the clinic. To create such an algorithm, this dissertation pursues the general class of active learning algorithms that includes Gaussian Process Upper Confidence Bound (GP-UCB, Srinivas et al., 2010), developing the Gaussian Process Batch Upper Confidence Bound (GP-BUCB, Desautels et al., 2012) and Gaussian Process Adaptive Upper Confidence Bound (GP-AUCB) algorithms. This dissertation develops new theoretical bounds for the performance of these and similar algorithms, empirically assesses these algorithms against a number of competitors in simulation, and applies a variant of the GP-BUCB algorithm in closed-loop to control SCI therapy via epidural electrostimulation in four live rats. The algorithm was tasked with maximizing the amplitude of evoked potentials in the rats' left tibialis anterior muscle. These experiments show that the algorithm is capable of directing these experiments sensibly, finding effective stimuli in all four animals. Further, in direct competition with an expert human experimenter, the algorithm produced superior performance in terms of average reward and comparable or superior performance in terms of maximum reward. These results indicate that variants of GP-BUCB may be suitable for autonomously directing SCI therapy.