CD4 T cells are rapidly depleted from tuberculosis granulomas following acute SIV co-infection

The HIV-mediated decline in circulating CD4 T cells correlates with increased the risk of active tuberculosis (TB). However, HIV/Mycobacterium tuberculosis (Mtb) co-infected individuals also have an increased incidence of TB prior to loss of CD4 T cells in blood, raising the possibility that HIV co-infection leads to disruption of CD4 T cell responses at the site of lung infection before they are observed systemically. Here we used a rhesus macaque model of SIV/Mtb co-infection to study the early effects of acute SIV infection on CD4 T cells in pulmonary Mtb granulomas. Two weeks after SIV co-infection CD4 T cells were dramatically depleted from granulomas, before significant bacterial outgrowth, disease reactivation as measured by PET-CT imaging, or CD4 T cell loss in blood, airways, and lymph nodes. Mtb-specific CD4 T cells, CCR5-expressing, in granulomas were preferentially depleted by SIV infection. Moreover, CD4 T cells were preferentially depleted from the granuloma core and lymphocyte cuff relative to B cell-rich regions, and live imaging of granuloma explants showed that SIV co-infection reduced T cell motility. Thus, Mtb-specific CD4 T cells in pulmonary granulomas may be decimated before many patients even experience the first symptoms of acute HIV infection.

HIV Infection, AIDS and Vaccines

HIV (human immunodeficiency virus) is a retrovirus that infects CD4+ T cells of the human immune system. If the infection is not treated, these cells are destroyed, resulting in an acquired immunodeficiency, i.e., “AIDS” (acquired immunodeficiency syndrome). HIV owns a reverse transcriptase enzyme to convert its RNA into DNA, which is then integrated into the human genome – then undetectable by the immune system. Today, sexual transmission is the major route of HIV infection, while parenteral transmission (sharing needles among drug addicts; rarely blood transfusion) and perinatal transmission are also possible. Acute HIV infection is accompanied by infectious mononucleosis-like symptoms (fevers, rash, lymphadenopathy, sore throat, fatigue), followed by a chronic asymptomatic stage, with viral replication at low levels, followed years later by AIDS, characterized by a plethora of possible opportunistic infections and cancers that result from T-cell deficiency and finally in death within about 2–3 years. Antiretroviral treatment (ART) includes 6 main classes of medicines that affect different steps of viral activities. While no cure is possible, ART – and particularly “Highly active antiretroviral therapy” (HAART) – has made HIV infections a chronic disease and therapy also results in a reduction of transmission. A large variety of vaccine candidates have been assessed – including phase 3 studies – but for many reasons, none of them have been successful to date.

Ethical considerations for HIV remission clinical research involving participants diagnosed during acute HIV infection

HIV remission clinical researchers are increasingly seeking study participants who are diagnosed and treated during acute HIV infection—the brief period between infection and the point when the body creates detectable HIV antibodies. This earliest stage of infection is often marked by flu-like illness and may be an especially tumultuous period of confusion, guilt, anger, and uncertainty. Such experiences may present added ethical challenges for HIV research recruitment, participation, and retention. The purpose of this paper is to identify potential ethical challenges associated with involving acutely diagnosed people living with HIV in remission research and considerations for how to mitigate them. We identify three domains of potential ethical concern for clinicians, researchers, and ethics committee members to consider: 1) Recruitment and informed consent; (2) Transmission risks and partner protection; and (3) Ancillary and continuing care. We discuss each of these domains with the aim of inspiring further work to advance the ethical conduct of HIV remission research. For example, experiences of confusion and uncertainty regarding illness and diagnosis during acute HIV infection may complicate informed consent procedures in studies that seek to recruit directly after diagnosis. To address this, it may be appropriate to use staged re-consent procedures or comprehension assessment. Responsible conduct of research requires a broad understanding of acute HIV infection that encompasses its biomedical, psychological, social, and behavioral dimensions. We argue that the lived experience of acute HIV infection may introduce ethical concerns that researchers and reviewers should address during study design and ethical approval.

Generalized Pruritus and Gradual Loss of Vision as the Presenting Complaints of Acute HIV Infection: Management Challenges during COVID-19 Pandemic

Background. Although the prevalence of HIV is low in Bangladesh, there is a potential for an increased number of cases. This is because of high cross-border mobility (India and Myanmar) of people and increased injection drug abusers amongst youth in the cities and rural areas, HIV can present in many ways, from asymptomatic to advanced disease, including various atypical (generalized itching) and advanced (loss of vision) manifestations. A high degree of suspicion is required to diagnose HIV in a country like Bangladesh. Early diagnosis and prompt treatment are essential to have a better outcome. Methods. Here, we report two thought-provoking cases where patients were suffering from generalized itchy lesions (pruritic papular eruption) throughout the body for a long time and gradual loss of vision in another case. Results. Due to lack of suspicion, initially, HIV screening was not done. Both patients visited several health centres, but no diagnosis was made. Moreover, COVID-19 pandemic worsens the situation. Finally, they were diagnosed with HIV; unfortunately, one of them lost her vision due to CMV retinitis and another patient died of other complications. Conclusion. Ongoing COVID-19 pandemic put many challenges to ensure optimum care, especially for patients with long-sufferings like HIV. Clinicians have to have a very high degree of suspicion while dealing with patients presented with rare manifestations, particularly in a low endemic clinical setting.

897. Trends and Correlation of HIV-1 Reservoir in Acute HIV Infection and Chronic HIV Infection in China

Background Among acute HIV infection （AHI）and chronic HIV infection（CHI）,the association of HIV-1 DNA and HIV-1 RNA is currently a hot spot of concern. We studied HIV-1 DNA levels in patients with AHI and CHI before initiation of ART to explore the growth characteristics of the HIV reservoir. Methods From 2016/10/31 to 2020/11/23, 97 patients were enrolled in the first hospital of Changsha in China. According to the patient’s epidemiological history, HIV-1 antibody conversion time, presence of opportunistic infection（OI）, to determine whether the patients were in the acute or chronic infection period, and divided into two arms: AHI and CHI. Lleukomonocyte, HIV-1 RNA, and CD4/8 of all patients were collected. The HIV-1 DNA in peripheral blood mononuclear (PBMC) was detected by PCR-Fluorescence Probing. The results were analyzed by SPSS 22.0 and GraphPad Prism 8.0. P-value < 0.05 were statistically significant. Results 93 of 97 were male and 85 of 97 with sexual transmission. In AHI arm, the mean of HIV-1 RNA was 5.15 log10 copies/ml, and the mean of HIV-1 DNA was 2.83 log10 copies/106 PBMCs. In CHI Arm, the mean value of HIV-1 RNA was 4.90 log10 copies/ml, and the mean value of HIV-1 DNA was 3.19 log copies/106 PBMCs. The HIV-1 DNA of CHI group was higher than that of AHI group (p = 0.002) , but the HIV-1 RNA of CHI group was lower than that of AHI Group (p = 0.183) . There were no significant differences between AHI and CHI in age, sex, body weight, route of infection, ART, other viral infection, leukomonocyte, CD4+ T cell count, CD4+ T cell percentage, CD8+ T cell count, CD8+ T cell percentage and CD4/CD8 ratio (P > 0.05).In Group AHI, HIV-1 DNA was positively correlated with HIV-1 RNA (r = 0.548, p < 0.001), but not in Group CHI (r = 0.14, p = 0.347). Conclusion Patients with AHI have lower HIV-1 DNA levels and smaller viral reservoir than those with CHI. These data have illustrates the benefits of rapid treatment. The correlation between HIV-1 DNA and HIV-1 RNA in patients with acute infection is strong,the level of HIV-1 DNA increased with the increase of HIV-1 RNA level, but was not related to CD4 + T cells, CD8 + T cells and CD4/CD8 ratio. Disclosures All Authors: No reported disclosures

Cohort profile: the Netherlands Cohort Study on Acute HIV infection (NOVA), a prospective cohort study of people with acute or early HIV infection who immediately initiate HIV treatment

PurposeInitiation of combination antiretroviral therapy (cART) during acute or early HIV-infection (AEHI) limits the size of the viral reservoir and preserves immune function. This renders individuals who started cART during AEHI promising participants in HIV-cure trials. Therefore, we established a multicentre prospective cohort study in the Netherlands that enrols people with AEHI. In anticipation of future cure trials, we will longitudinally investigate the properties of the viral reservoir size and HIV-specific immune responses among cohort participants.ParticipantsParticipants immediately initiate intensified cART: dolutegravir, emtricitabine/tenofovir and darunavir/ritonavir (DRV/r). After 4 weeks, once baseline resistance data are available, DRV/r is discontinued. Three study groups are assembled based on the preparedness of individuals to participate in the extensiveness of sampling. Participants accepting immediate treatment and follow-up but declining additional sampling are included in study group 1 (‘standard’) and routine diagnostic procedures are performed. Participants willing to undergo blood, leukapheresis and semen sampling are included in study group 2 (‘less invasive’). In study group 3 (‘extended’), additional tissue (gut-associated lymphoid tissue, peripheral lymph node) and cerebrospinal fluid sampling are performed.Findings to dateBetween 2015 and 2020, 140 individuals with AEHI have been enrolled at nine study sites. At enrolment, median age was 36 (IQR 28–47) years, and 134 (95.7%) participants were men. Distribution of Fiebig stages was as follows: Fiebig I, 3 (2.1%); II, 20 (14.3%); III, 7 (5.0%); IV, 49 (35.0%); V, 39 (27.9%); VI, 22 (15.7%). Median plasma HIV RNA was 5.9 (IQR 4.7–6.7) log10 copies/mL and CD4 count 510 (IQR 370–700) cells/mm3. Median time from cART initiation to viral suppression was 8.0 (IQR 4.0–16.0) weeks.Future plansThe Netherlands Cohort Study on Acute HIV infection remains open for participant enrolment and for additional sites to join the network. This cohort provides a unique nationwide platform for conducting future in-depth virological, immunological, host genetic and interventional studies investigating HIV-cure strategies.

Acute HIV infection syndrome mimicking COVID-19 vaccination side effects: a case report

Background Symptoms of primary HIV infection, including fever, rash, and headache, are nonspecific and are often described as flu-like. COVID-19 vaccination side effects, such as fever, which occur in up to 10% of people following COVID-19 vaccination, can make the diagnosis of acute HIV infection even more challenging. Case presentation A 26-year-old man presented with fever and headache following COVID-19 vaccination. The symptoms were initially thought to be vaccine side effects. A diagnostic workup was conducted due to persisting fever and headache > 72 h following vaccination, and he was diagnosed with Fiebig stage II acute HIV infection, 3 weeks after having unprotected anal intercourse with another man. Conclusion Thorough anamnesis is key to estimating the individual risk of primary HIV infection, in patients presenting with flu-like symptoms. Early diagnosis and initiation of antiretroviral therapy is associated with better prognosis and limits transmission of the disease.