Acute retroviral syndrome is associated with lower CD4 + T cell nadir and delayed viral suppression, which are blunted by immediate antiretroviral therapy initiation.

OBJECTIVES: To describe the prevalence of acute retroviral syndrome (ARS) and associated findings during primary HIV, and explore the relationship of ARS to clinical, virological, and immunological outcomes within a longitudinal screen, retest and treat study that minimized ascertainment bias. DESIGN: We evaluated ARS symptoms and signs among 216 persons with acute and early incident HIV within the Sabes study of timing of antiretroviral therapy (ART) initiation during primary HIV in Peru. METHODS: We evaluated patient reported symptoms and signs during primary HIV and used logistic regression and generalized linear models to evaluate associations with CD4 + and CD8 + T cell counts, HIV viral load, and a panel of 23 soluble markers of immune activation. RESULTS: Sixty-one percent of participants had at least one ARS finding and 35% had at least 3. More ARS findings were reported in those enrolled within a month of estimated date of detectable infection (EDDI). Having more ARS signs/symptoms was associated with increased risk of CD4 + cell decrease below 350 cells/ml within the first 24 weeks, failure to suppress HIV viral load, and was most strongly associated with elevated IP-10. Immediate ART blunted effects on symptoms, CD4 + cell count and viral load, as associations were strongest in the arm that started ART after 24 weeks. Detrimental associations of ARS with CD4 + counts, and CD4 + /CD8 + ratio were not maintained at 2 or 4 years. CONCLUSIONS: ARS has marked associations with short-term immunologic function and virologic suppression, which were mitigated in participants randomized to initiate ART immediately during primary infection.

A Stronger Innate Immune Response During Hyperacute Human Immunodeficiency Virus Type 1 (HIV-1) Infection Is Associated With Acute Retroviral Syndrome.

BACKGROUND: Acute retroviral syndrome (ARS) is associated with human immunodeficiency virus type 1 (HIV-1) subtype and disease progression, but the underlying immunopathological pathways are poorly understood. We aimed to elucidate associations between innate immune responses during hyperacute HIV-1 infection (hAHI) and ARS. METHODS: Plasma samples obtained from volunteers (≥18.0 years) before and during hAHI, defined as HIV-1 antibody negative and RNA or p24 antigen positive, from Kenya, Rwanda, Uganda, Zambia, and Sweden were analyzed. Forty soluble innate immune markers were measured using multiplexed assays. Immune responses were differentiated into volunteers with stronger and comparatively weaker responses using principal component analysis. Presence or absence of ARS was defined based on 11 symptoms using latent class analysis. Logistic regression was used to determine associations between immune responses and ARS. RESULTS: Of 55 volunteers, 31 (56%) had ARS. Volunteers with stronger immune responses (n = 36 [65%]) had increased odds of ARS which was independent of HIV-1 subtype, age, and risk group (adjusted odds ratio, 7.1 [95% confidence interval {CI}: 1.7-28.8], P = .003). Interferon gamma-induced protein (IP)-10 was 14-fold higher during hAHI, elevated in 7 of the 11 symptoms and independently associated with ARS. IP-10 threshold >466.0 pg/mL differentiated stronger immune responses with a sensitivity of 84.2% (95% CI: 60.4-96.6) and specificity of 100.0% (95% CI]: 90.3-100.0). CONCLUSIONS: A stronger innate immune response during hAHI was associated with ARS. Plasma IP-10 may be a candidate biomarker of stronger innate immunity. Our findings provide further insights on innate immune responses in regulating ARS and may inform the design of vaccine candidates harnessing innate immunity.

The life-threatening eruption in HIV and immunosuppression.

Immunosuppressed patients frequently have skin diseases of mild to moderate intensity. Diagnosis as well as treatment should be performed early to avoid important complications for these patients. Skin eruptions are among these problems. Life-threatening eruptions in HIV and other types of immunosuppression range from acute retroviral syndrome to drug eruptions; immune reconstitution inflammatory syndrome; infection by virus, protozoan, bacteria, or fungi; inflammatory and immune dermatoses; and neoplasia. All of these are discussed in this group of patients.

Síndrome retroviral aguda en un adolescent amb herpes genital / Síndrome retroviral agudo en un adolescente con herpes genital / Acute retroviral syndrome in an adolescent with genital herpes

Introducció: La infecció aguda pel virus de la immunodeficiència humana (VIH) cursa amb clínica inespecífica i transitòria tipus síndrome mononucleòsica. És poc freqüent trobar un cas de VIH en l'edat pediàtrica i, a més, l'adolescent poques vegades expressa de forma espontània una exposició de risc. Per això és important considerar la infecció per VIH, sobretot si es detecten altres infeccions de transmissió sexual. Cas clínic: Adolescent de 13 anys amb discapacitat intel·lectual lleu, que consulta per febre, odinofàgia, astènia, miàlgies, anorèxia, vòmits i diarrea de 5 dies d'evolució. Després d'insistir en l'anamnesi, explica que els darrers dos dies apareix exantema a tronc i úlceres al penis, i que va tenir una única relació homosexual no consentida fa dos mesos. En l'exploració destaca exantema maculoeritematós al tronc, hiperèmia faríngia, adenopaties generalitzades i úlceres doloroses al gland i al prepuci. La reacció en cadena de la polimerasa al frotis de les lesions genitals és positiva per a virus herpes simple 1. El test ràpid d'anticossos pel VIH resulta indeterminat i el test confirmatori per immunocromatografia és negatiu. Presenta càrrega viral del VIH de 1.681.383 còpies/mL, test d'immunoassaig de 4a generació (inclou detecció anticossos VIH i antigen p24) positiu i recompte de limfòcits CD4 de 327 cèl·lules/μL. Rep tractament amb aciclovir i teràpia antiretroviral amb tenofovir, emtricitabina i darunavir/cobicistat, que després de l'alta hospitalària s'administra de forma supervisada al domicili. Comentaris: El pediatre ha d'estar alerta per reconèixer la infecció aguda per VIH i altres malalties de transmissió sexual en l'adolescent. El diagnòstic de la infecció evita la transmissió als altres, i l'inici precoç de la teràpia antiretroviral millora el pronòstic de la malaltia

Introducción: La infección aguda por el virus de la inmunodeficiencia humana (VIH) cursa con clínica inespecífica y transitoria tipo síndrome mononucleósico. Es poco frecuente encontrarse con un caso de VIH en la edad pediátrica y, además, el adolescente pocas veces revela de forma espontánea una exposición de riesgo. Por ello es importante considerar la infección por VIH, sobre todo si se detectan otras infecciones de transmisión sexual. Caso clínico: Adolescente de 13 años con discapacidad intelectual leve, que consulta por fiebre, odinofagia, astenia, mialgias, anorexia, vómitos y diarrea de 5 días de evolución. Tras insistir en la anamnesis, explica que en los últimos dos días aparece exantema en tronco y úlceras en pene, y que tuvo una única relación homosexual no consentida hace dos meses. En la exploración destaca exantema maculoeritematoso en tronco, hiperemia faríngea, adenopatías generalizadas y úlceras dolorosas en glande y prepucio. La reacción en cadena de la polimerasa en frotis de las lesiones genitales es positiva para virus herpes simple 1. El test rápido de anticuerpos VIH resulta indeterminado y el test confirmatorio por inmunocromatografía es negativo. Presenta carga viral del VIH de 1.681.383 copias/ml, test de inmunoensayo de 4ª generación (incluye detección anticuerpos VIH y antígeno p24) positivo y recuento de linfocitos CD4 de 327 células/μl. Recibe tratamiento con aciclovir y terapia antirretroviral con tenofovir, emtricitabina y darunavir/cobicistat, que tras el alta hospitalaria se administra de forma supervisada en domicilio. Comentarios: El pediatra debe estar alerta para reconocer la infección aguda por VIH y otras enfermedades de transmisión sexual en el adolescente. El diagnóstico de la infección evita la transmisión a otros y el inicio precoz de la terapia antirretroviral mejora el pronóstico de la enfermedad

Introduction: Acute human immune deficiency virus (HIV) infection is typically described as a transient and non-specific mononucleosis like syndrome. This acute presentation is rare in pediatrics, and adolescents rarely report a risk exposure. Thus, it is important to consider HIV infection specially if other sexually transmitted diseases are diagnosed. Case report: A 13-year-old boy with mild intellectual disability, presented with a 5-day history of fever, sore throat, asthenia, myalgia, anorexia, vomiting and diarrhea. Upon questioning, the patient disclosed having a rash on the trunk and penis ulcers for the last two days, and that he had non-consensual sex with a man two months prior. Physical examination was notable for a macular rash on the trunk, pharyngitis, generalized lymphadenopathy and painful ulcers on the glans and prepuce. Herpes simplex type 1 was detected in genital lesions by Polymerase Chain Reaction. Rapid HIV test was indeterminate and confirmatory test by immunochromatography was negative. Plasma HIV viral load was 1.681.383 copies/ml, 4th generation immunoassay (including HIV antibodies and p24 antigen detection) was positive and CD4 lymphocyte count was 327 cells/μl. He was treated with acyclovir and started antiretroviral therapy regimen, consisting of tenofovir, emtricitabine and darunavir/cobicistat that was given under supervision at home after discharge. Comments: Pediatricians must be aware of the signs of acute HIV infection and other sexually transmitted diseases in adolescent patients. Prompt diagnosis helps to prevent further transmission and early antiretroviral therapy improves outcomes

Cardiovascular complications of HIV / Complicações cardiovasculares do HIV

With the advent of the antiretroviral therapy (ART), people infected with HIV are experiencing a significant increase in life expectancy. However, as this population ages, the morbidity and mortality due to events not related to HIV infection and/or treatment become increasingly clear. Cardiovascular diseases are among the major causes of death, and, thus, understanding the factors that trigger this situation is necessary. This review article will assess how the intrinsic and extrinsic factors related to HIV, ART and the associated risk factors can aid the epidemiological transition of mortality in this population. Moreover, we will present the studies on the epidemiology and pathogenesis of each clinical condition related to HIV-infected individuals, in addition to introducing the major markers of cardiovascular disease in this population. Finally, we will point the main issues to be addressed by health professionals for an adequate prognosis

Performance of the BioPlex 2200 HIV Ag-Ab assay for identifying acute HIV infection.

BACKGROUND: Assays that detect HIV antigen (Ag) and antibody (Ab) can be used to screen for HIV infection. OBJECTIVES: To compare the performance of the BioPlex 2200 HIV Ag-Ab assay and two other Ag/Ab combination assays for detection of acute HIV infection. STUDY DESIGN: Samples were obtained from 24 individuals (18 from the US, 6 from South Africa); these individuals were classified as having acute infection based on the following criteria: positive qualitative RNA assay; two negative rapid tests; negative discriminatory test. The samples were tested with the BioPlex assay, the ARCHITECT HIV Ag/Ab Combo test, the Bio-Rad GS HIV Combo Ag-Ab EIA test, and a viral load assay. RESULTS: Twelve (50.0%) of 24 samples had RNA detected only ( > 40 to 13,476 copies/mL). Ten (43.5%) samples had reactive results with all three Ag/Ab assays, one sample was reactive with the ARCHITECT and Bio-Rad assays, and one sample was reactive with the Bio-Rad and BioPlex assays. The 11 samples that were reactive with the BioPlex assay had viral loads from 83,010 to >750,000 copies/mL; 9/11 samples were classified as Ag positive/Ab negative by the BioPlex assay. CONCLUSIONS: Detection of acute HIV infection was similar for the BioPlex assay and two other Ag/Ab assays. All three tests were less sensitive than a qualitative RNA assay and only detected HIV Ag when the viral load was high. The BioPlex assay detected acute infection in about half of the cases, and identified most of those infections as Ag positive/Ab negative.

Acute Retroviral Syndrome Is Associated With High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments.

Background: Many individuals with acute human immunodeficiency virus infection (AHI) experience acute retroviral syndrome (ARS), which is associated with adverse long-term clinical outcomes. Methods: Participants presenting for voluntary human immunodeficiency virus (HIV) testing were enrolled during AHI in Bangkok, Thailand. ARS was defined by ≥3 qualifying signs/symptoms. HIV burden, immunophenotypes, and biomarkers were stratified by ARS diagnosis at enrollment and after up to 96 weeks of antiretroviral therapy (ART). Results: From 212382 samples screened, 430 participants were enrolled during AHI, including 335 (78%) with ARS. Median age was 26 years and 416 (97%) were men. Sixty (14%) underwent sigmoid biopsy and 105 (24%) underwent lumbar puncture during AHI. Common symptoms included fever (93%), fatigue (79%), pharyngitis (67%), and headache (64%). Compared to those without ARS, participants with ARS were in later Fiebig stages with higher HIV RNA in blood, colon, and cerebrospinal fluid; higher total HIV DNA in blood; CD4 depletion in blood and colon; and elevated plasma tumor necrosis factor alpha (TNF-α), C-reactive protein, and D-dimer (all P < .05). Subgroup analyses of Fiebig I/II participants (95 with ARS, 69 without) demonstrated similar findings. After 96 weeks of ART, TNF-α and interleukin 6 were elevated in the ARS group (P < .05) but other biomarkers equilibrated. Conclusions: ARS was associated with high viral burden, CD4 depletion, and immune activation across multiple body compartments during AHI and prior to ART. Persistent inflammation despite suppressive ART could contribute to increased morbidity in individuals who experience ARS.

Differences in acute retroviral syndrome by HIV-1 subtype in a multicentre cohort study in Africa.

OBJECTIVE: Symptoms of acute retroviral syndrome (ARS) may be used to identify patients with acute HIV-1 infection who seek care. ARS symptoms in African adults differ by region. We assessed whether reporting of ARS was associated with HIV-1 subtype in a multicentre African cohort study representing countries with predominant HIV-1 subtypes A, C, and D. METHODS: ARS symptoms were assessed in adults enrolling within 6 weeks after the estimated date of infection in an acute and early HIV-1 infection cohort study. HIV-1 subtype was determined by POL genotyping. We used log-binomial regression to compare ARS symptom prevalence among those with subtype A vs. C or D, adjusting for sex, time since enrolment, and enrolment viral load. RESULTS: Among 183 volunteers ascertained within 6 weeks after estimated date of infection, 77 (42.0%) had subtype A, 83 (45.4%) subtype C, and 23 (12.6%) subtype D infection. Individuals with subtype A were 1.40 (95% confidence interval: 1.17, 1.68) times as likely as individuals with subtypes C or D to report any ARS symptoms; each individual symptom other than rash was also more prevalent in subtype A than in subtype C or D, with prevalence ratios ranging from 1.94 (1.40, 2.70) for headache to 4.92 (2.24, 10.78) for lymphadenopathy. CONCLUSION: Individuals with subtype A were significantly more likely than individuals with subtypes C or D to report any ARS symptoms. HIV-1 subtypes may help explain differences in ARS that have been observed across regions in Africa, and may impact the yield of symptom-based screening strategies for acute HIV infection detection.

Síndromes de mononucleose / Mononucleosis syndromes

Este artigo aborda o diagnóstico diferencial entre algumas das principais causas de síndrome mononucleose-like, bem como o seu manejo inicial pelo clínico.

This article discusses the differential diagnosis between some of the main causes of mononucleosis-like illnesses, as well as their initial management by the clinician.