A simple algorithm for selecting cases to investigate acute and early HIV infections in low- and middle-income countries

We documented the outcome of an over 10-year effort to diagnose acute and early HIV infections (AEHI) in an Infectious Diseases Outpatient Clinic with limited resources. Of a total of 132 cases, 119 HIV-RNA tests were performed from 2017–2020, 12 cases were identified, using a simple algorithm: risk exposure of six weeks or less before the visit and/or symptoms compatible with acute retroviral syndrome 7–30 days after exposure and/or undetermined 3rd generation rapid diagnostic test or serology. AEHI diagnoses varied from 2.4% among asymptomatic to 25% for undetermined serology cases using a simple screening applicable to different settings.

Intracranial hypertension and papilloedema as a complication to low antiretroviral therapy adherence in a man living with chronic HIV

We describe a 61-year-old man living with HIV on antiretroviral therapy (ART), who presented with headache, dizziness and blurred vision. Latest CD4+ cell count 3 months prior to admission was 570×106 cells/mL and HIV viral load <20 copies/mL. The patient was diagnosed with cerebrospinal fluid (CSF) lymphocytic pleocytosis, raised intracranial pressure and papilloedema. Neuroimaging showed normal ventricular volume and no mass lesions, suggesting (1) neuroinfection (2) idiopathic intracranial hypertension or (3) retroviral rebound syndrome (RRS) as possible causes. Neuroinfection was ruled out and idiopathic intracranial hypertension seemed unlikely. Elevated plasma HIV RNA level was detected consistent with reduced ART adherence prior to admission. RRS is a virological rebound after ART interruption, which can mimic the acute retroviral syndrome of acute primary infection. To the best of our knowledge, we describe the second case of RRS presenting as CSF lymphocytic pleocytosis and elevated intracranial pressure after low ART adherence.

A Stronger Innate Immune Response During Hyperacute HIV-1 Infection is associated with ACUTE retroviral syndrome

Background Acute retroviral syndrome (ARS) is associated with 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 analysed. 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 eleven 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% CI: 1.7–28.8], p=0.003). IP-10 was fourteen-fold higher during hAHI, elevated in seven of the eleven symptoms, and independently associated with ARS. IP-10 threshold &gt;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.

Atypical Acute Retroviral Syndrome Presenting as a Facial Palsy

Acute retroviral syndrome (ARS) refers to signs and symptoms present during acute human immunodeficiency virus (HIV) infection. Historically, ARS has been characterized as a mononucleosis-like illness. However, ARS may present with typical (i.e., mononucleosis-like) or atypical signs and symptoms. Here, we review typical and atypical ARS and discuss a 30-year-old man who first presented with a facial palsy and returned 2 years later with oral hairy leukoplakia, at which time he was found to have HIV and acquired immunodeficiency syndrome (AIDS). We suggest that facial palsies should pique clinical suspicion for HIV, especially in the context of recent or concurrent flu- or mononucleosis-like illness.

Acute Hepatitis A Outbreak Among Men Who Have Sex With Men in Krakow, Poland; February 2017–February 2018

Since February 2017 in Poland, an increasing number of acute hepatitis A (AHA) cases have been reported; a noteworthy increase to 3,072 cases of AHA in 2017 compared to 35 cases in 2016 was reported by the National Institute of Public Health (NIPH). The aim of this study was to evaluate the demographic features, clinical manifestations, laboratory results, and sexually transmitted coinfections. All cases of AHA diagnosed between February 2017 and February 2018 at the University Hospital in Krakow were analyzed. A total of 119 cases of hepatitis A virus (HAV) were reported; 105 (88%) were males and 14 (12%) were females, with a mean age 31 years (range 19–62). In 84 patients (71%), the HAV was transmitted by oral–anal sexual contact between men. Six women were infected by close house contact with men infected with HAV. The route of transmission was not identified for 29 cases, and 88 patients (74%) required hospitalization. Among the cases, the following coinfections were already diagnosed: HIV 36 patients (30%), chronic hepatitis C virus (HCV) 4 patients (3%), and chronic hepatitis B virus (HBV) 2 patients (1.5%). During AHA diagnosis, some new sexually transmitted infections (STIs) were detected; syphilis eight patients (6.7%), HIV/syphilis seven patients (6%), HIV//HCV/syphilis one patient, and acute retroviral syndrome/ Shigella flexneri one patient. Overall, AHA outbreak in Poland in 2017 affected primarily men who have sex with men (MSM) and was connected with oral–anal sexual contacts, and the majority of patients did not have HAV vaccination. These results show a clear need for routinely offering HAV vaccination to at-risk populations and that awareness among health-care workers about HAV sexual transmission may help introduce prevention methods.

Analytical treatment interruption in chronic HIV-1 infection: time and magnitude of viral rebound in adults with 10 years of undetectable viral load and low HIV-DNA (APACHE study)

ObjectivesDespite the fact that there are individuals who have chronic HIV infection, few studies have investigated ART interruption in this setting. The aim of this study was to evaluate the ability to spontaneously control viral replication during analytical treatment interruption (ATI) in adults with chronic HIV-1 infection, on ART, with suppressed viraemia for >10 years and with a low reservoir.Patients and methodsThis was a prospective, open-label, single-arm, non-randomized, proof-of-concept study (NCT03198325) of subjects with chronic HIV-1 infection, HIV-RNA <50 copies/mL for ≥10 years, without residual viraemia for ≥5 years, CD4+ >500 cells/mm3, HIV-DNA <100 copies/106 PBMCs and without comorbidities or AIDS-defining diseases. Enrolled patients were strictly monitored. The ART regimen in use at ATI was resumed in the case of confirmed viral rebound (CVR, two consecutive HIV-RNA >50 copies/mL). Results are reported as median (IQR).ResultsNine patients underwent ATI. All participants experienced CVR [4.84 (IQR: 3.47–6.47) HIV-RNA log10 copies/mL] after ATI at a median time of 21 days (range 14–56) and restarted ART. After ART resumption, all the subjects achieved HIV-RNA <50 copies/mL in a median of 88 days (range 15–197). No serious adverse event occurred; one subject experienced acute retroviral syndrome. No significant correlation between baseline factors and time to viral rebound was observed, while the magnitude of viral rebound was significantly associated with pre-ART HIV-1 RNA (Spearman r = 0.786, P = 0.036), nadir CD4+ (Spearman r = −0.800, P = 0.010), baseline CD4+ (Spearman r = −0.667, P = 0.049) and years with undetectable viral load (Spearman r = −0.717, P = 0.030).ConclusionsDespite a long period of HIV viral load suppression and a low viral reservoir, early and consistent viral rebound was observed during ATI in all subjects.

Acute Retroviral Syndrome Presenting with Hemolytic Anemia Induced by G6PD Deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme defect described in humans. Hemolysis in affected patients is usually triggered by circumstances involving free radical damage. While acute HIV infection is known to be a state of overwhelming oxidative stress, virus-induced hemolytic events in G6PD-deficient patients has rarely been reported. Despite an estimated overall prevalence of 6.8%–13% of this disorder in the HIV population, clinically significant hemolysis has been largely attributed to the use of offending medications rather than HIV infection itself. Here, we present a patient whose first episode of G6PD deficiency-associated hemolysis occurred as the main presentation of acute HIV infection.