CD4 T-cell Count Research Articles

Dramatic Improvement of MRI Abnormalities of HIV Dementia after Suppressive Antiretroviral Therapy (S25.002)

<h3>Objective:</h3> Not applicable. <h3>Background:</h3> A 59-year-old man diagnosed with HIV 26 years prior and a long history of antiretroviral therapy (ART) non-adherence presented with subacute cognitive decline. A neurologic workup including cerebrospinal fluid testing showed no evidence of opportunistic infections. He was admitted to an assisted care facility where he restarted ART. However, he remained viremic and was referred to the National Institutes of Health (NIH). On admission to the NIH, he had an HIV plasma viral load of 28,056 copies/mL and CD4 T-cell count of 5 cells/μL. He was started on a new ART regimen with increased central nervous system penetration (etravirine, dolutegravir, darunavir/cobicistat, tenofovir/emtricitabine). MRI revealed extensive leukoencephalopathy and volume loss, consistent with HIV encephalopathy. Comprehensive neuropsychological testing revealed significant deficits in all cognitive domains, including learning, memory, attention, executive function, and psychomotor speed. The patient was followed for two years, during which time he achieved and sustained viral suppression (&lt;40 copies/mL) and reached a CD4 T-cell count of 197 with ART. A repeat MRI showed profound improvement in the white matter signal abnormality. Repeat neuropsychological testing demonstrated notable improvements in several tests of attention, information processing, and psychomotor speed, but continued difficulty in most other cognitive domains. <h3>Design/Methods:</h3> Not applicable. <h3>Results:</h3> Not applicable. <h3>Conclusions:</h3> While current ART regimens are highly effective in reducing the incidence of HIV-associated neurologic complications, their role in reversing the MRI abnormalities seen in HIV encephalopathy remains unclear. In this case, we tracked HIV encephalopathy in the current era of effective ART with serial MRI evaluations. Our results provide a rare example of dramatic reduction of periventricular white matter hyperintensities and improved performance in a subset of cognitive domains. Providers encountering white matter abnormalities in patients with treated HIV should consider this legacy effect in evaluating whether disease is progressive, or as in this case, improved. <b>Disclosure:</b> Ms. Dietrich has nothing to disclose. Miss Laidlaw has nothing to disclose. Dr. Hammoud has nothing to disclose. Dr. Pau has nothing to disclose. Dr. Smith has nothing to disclose.

Efficacy and safety of ainuovirine versus efavirenz combination therapies with lamivudine/tenofovir disoproxil fumarate for medication of treatment-naïve HIV-1-positive adults: week 48 results of a randomized controlled phase 3 clinical trial followed by an open-label setting until week 96

Ainuovirine (ANV) is a new non-nucleoside reverse transcriptase inhibitor (NNRTI), which was initially synthesized in Korea and later further developed in both Korea and China. A randomized, double-blind, double-dummy, positive parallel group, non-inferiority, phase 3 trial was conducted in 7 sites across China. Eligible HIV-1-positive antiretroviral therapy (ART)-naïve adults aged 18-65 years were randomly assigned in a 1:1 ratio to receive tenofovir disoproxil fumarate and lamivudine (TDF+3TC) in combination with either ANV (ANV group) or efavirenz (EFV group) for up to 48 weeks. Subsequently, participants in both groups received one of the two drug combinations according to their choice until week 96 in an observational study under an open-label setting. The primary endpoint was the proportion of participants achieving HIV RNA <50 copies/mL at week 48, with non-inferiority pre-specified at a margin of 10%. The secondary efficacy endpoints were logarithmic changes in HIV RNA, percentage of participants with HIV RNA levels ≤400 copies/mL and changes in the CD4 T-cell count after 48 and 96 weeks of treatment, as well as the percentage of participants with HIV RNA levels <50 copies/mL at 96 weeks of treatment. Safety endpoints were the incidence of adverse events and laboratory abnormalities evaluated according to the Division of AIDS criteria. This study was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR1800019041). Between November 27, 2018 and March 11, 2021, a total of 826 participants were screened, and 630 were finally enrolled and randomly assigned (1:1) to either ANV (n=315) or EFV (n=315) groups. The mean age was 30.6±9.4 years and most participants were male (94.6%). At week 48, 274 (87.0%) of 315 participants in the ANV group and 288 (91.7%) of 314 in the EFV group achieved HIV-1 RNA <50 copies/mL and non-inferiority was established (difference:-4.7%, 95% CI:-9.6 to 0.1%). In the period, 293 participants continued to take the ANV regimen and 287 switched from the EFV to the ANV regimen. During the open-label period, 92.5% (271/293) of participants in the continued ANV group and 95.1% (273/287) in the ANV to EFV transfer group remained virologically suppressed (HIV-1 RNA <50 copies/mL) at week 96 (p=0.189). The incidence of NNRTI treatment-related adverse events (TEAEs) at week 48 was 67.6% in 315 participants in the ANV group, which was significantly lower than in 91.4% of 314 participants in the EFV group (p<0.001). The most common TEAEs (weeks 0-48) were dizziness (10.5%) and dyslipidemia (22.2%) in the ANV group vs. 51.0% and 34.4% in the EFV group, respectively, followed by transaminase elevation (9.2% vs. 29.0%), γ-glutamyl transferase elevation (8.3% vs. 19.1%), and rash (7.9% vs. 18.8%) (all p<0.001). After switching from EFV to ANV, TEAEs in the former EFV participants were significantly reduced in the following observational period of 48-96 weeks. The week 48 results indicated that the efficacy of ANV was non-inferior to EFV when combined with two NRTIs. The per-protocol risk difference at week 48 for the primary endpoint also supported non-inferiority. TEAEs in ANV treated participants were less frequent with regard to liver toxicity, dyslipidemia, neuropsychiatric symptoms and rash compared to the EFV group during the first 48 weeks of therapy. The effects were maintained during the 48-96 weeks of therapy. Jiangsu Aidea Pharmaceutical Co., Ltd.

Correlation between CD4 T-Cell Counts and Seroconversion among COVID-19 Vaccinated Patients with HIV: A Meta-Analysis.

To evaluate the potential factors for predicting seroconversion due to the coronavirus disease 2019 (COVID-19) vaccine in people living with HIV (PLWH). We searched the PubMed, Embase and Cochrane databases for eligible studies published from inception to 13th September 2022 on the predictors of serologic response to the COVID-19 vaccine among PLWH. This meta-analysis was registered with PROSPERO (CRD42022359603). A total of 23 studies comprising 4428 PLWH were included in the meta-analysis. Pooled data demonstrated that seroconversion was about 4.6 times in patients with high CD4 T-cell counts (odds ratio (OR) = 4.64, 95% CI 2.63 to 8.19) compared with those with low CD4 T-cell counts. Seroconversion was about 17.5 times in patients receiving mRNA COVID-19 vaccines (OR = 17.48, 95% CI 6.16 to 49.55) compared with those receiving other types of COVID-19 vaccines. There were no differences in seroconversion among patients with different ages, gender, HIV viral load, comorbidities, days after complete vaccination, and mRNA type. Subgroup analyses further validated our findings about the predictive value of CD4 T-cell counts for seroconversion due to COVID-19 vaccines in PLWH (OR range, 2.30 to 9.59). The CD4 T-cell counts were associated with seroconversion in COVID-19 vaccinated PLWH. Precautions should be emphasized in these patients with low CD4 T-cell counts, even after a complete course of vaccination.

Immunogenicity of COVID-19 Vaccination in People Living with HIV: Progress and Challenges

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in numerous confirmed cases and deaths worldwide. Recent studies have shown that people living with HIV (PLWH) are prone to develop severe illness and poor outcomes if they experience coronavirus disease 2019 (COVID-19), especially those with uncontrolled viremia and low CD4 T-cell count. Therefore, many countries prioritized PLWH for COVID-19 vaccination. However, lower magnitude or faster waning humoral immune responses elicited by other vaccines have been documented in PLWH, raising concerns regarding the efficacy of the COVID-19 vaccine in these specific populations. Here, we summarize the current progress in the immunogenicity and efficacy of different types of SARS-CoV-2 vaccinations in PLWH and highlight several challenges faced by PLWH in the current COVID-19 pandemics.

Cerebrospinal fluid virology in people with HIV.

Our objectives were to investigate the recent frequency of cerebrospinal fluid (CSF) HIV RNA escape and other CSF viral nucleic acid detection in people with HIV with neurological symptoms and to assess associated clinical factors. This was a retrospective cohort analysis of people with HIV who underwent CSF examination for clinical indications between 2017 and 2022. Individuals were identified from pathology records, and clinical data were recorded. CSF HIV RNA escape was defined as CSF HIV RNA concentrations greater than in plasma. CSF viral screen included herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV), Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and JC virus. When cases were detected in five or more people with HIV, associated clinical factors were assessed using linear regression modelling. CSF HIV RNA escape was observed in 19 of 114 individuals (17%) and was associated with the presence of HIV drug resistance mutations and non-integrase strand transfer inhibitor-based antiretroviral therapy (p < 0.05 for all) when compared to people with HIV without escape. Positive viral nucleic acid testing included EBV (n=10), VZV (3), CMV (2), HHV-6 (2) and JC virus (4). Detectable CSF EBV was not considered related to neurological symptoms and was associated with concomitant CSF infections in eight of ten individuals and with CSF pleocytosis, previous AIDS, lower nadir and current CD4 T-cell count (p < 0.05 for all). In people with HIV with neurological symptoms, the frequency of CSF HIV RNA escape remains similar to that in historical reports. Detectable EBV viral nucleic acid in the CSF was observed frequently and, in the absence of clinical manifestations, may be a consequence of CSF pleocytosis.

Characterization of Rare Spontaneous Human Immunodeficiency Virus Viral Controllers Attending a National United Kingdom Clinical Service Using a Combination of Serology and Molecular Diagnostic Assays.

We report outcomes and novel characterization of a unique cohort of 42 individuals with persistently indeterminate human immunodeficiency virus (HIV) status, the majority of whom are HIV viral controllers. Eligible individuals had indeterminate or positive HIV serology, but persistently undetectable HIV ribonucleic acid (RNA) by commercial assays and were not taking antiretroviral therapy (ART). Routine investigations included HIV Western blot, HIV viral load, qualitative HIV-1 deoxyribonucleic acid (DNA), coinfection screen, and T-cell quantification. Research assays included T-cell activation, ART measurement, single-copy assays detecting HIV-1 RNA and DNA, and plasma cytokine quantification. Human immunodeficiency virus seropositivity was defined as ≥3 bands on Western blot; molecular positivity was defined as detection of HIV RNA or DNA. Human immunodeficiency virus infection was excluded in 10 of 42 referrals, remained unconfirmed in 2 of 42, and was confirmed in 30 of 42, who were identified as HIV elite controllers (ECs), normal CD4 T-cell counts (median 820/mL, range 805-1336), and normal CD4/CD8 ratio (median 1.8, range 1.2-1.9). Elite controllers had a median duration of elite control of 6 years (interquartile range = 4-14). Antiretroviral therapy was undetected in all 23 subjects tested. Two distinct categories of ECs were identified: molecular positive (n = 20) and molecular negative (n = 10). Human immunodeficiency virus status was resolved for 95% of referrals with the majority diagnosed as EC. The clinical significance of the 2 molecular categories among ECs requires further investigation.

Birth Country Influences the Choice of Antiretroviral Therapy in HIV-Infected Individuals: Experience From a French HIV Centre.

To assess whether antiretroviral therapy (ART) prescriptions differ between naive and virally suppressed HIV patients born in France (PBFs) and in Sub-Saharan Africa (PBSSAs). Observational single-center study. We included all PBFs and PBSSAs who entered into care at Pitié-Salpêtrière Hospital, Paris, France, from 01/01/2000 to 31/12/2018, with plasma HIV-RNA>200 copies/mL. We first compared the initial ART in naive PBFs and PBSSAs. Second, we compared the last-prescribed ART (including drug-reduced ART: daily 2-drug regimens, daily 1-drug regimens and intermittent 3-drug regimens) in virally suppressed PBFs and PBSSAs, by focusing on patients in care in 2018 with HIV-RNA <50 copies for at least 24 months. A univariable and multivariable logistic regression model was used to assess the impact of geographical origin on ART prescriptions. A total of 1944 naive patients were included (915 PBSSAs and 1029 PBFs). PBSSAs were more frequently women, hepatitis B coinfected, with a lower pretherapeutic CD4 T-cell count, and most had tuberculosis at HIV diagnosis. After adjustment for confounders, PBSSAs were more likely to receive a first-line protease inhibitor-based regimen (OR 1.61, 95% CI: 1.31 to 1.98), and less likely to receive an integrase inhibitor-based regimen (OR 0.61, 95% CI: 0.42 to 0.88). Of the 968 virally suppressed patients (431 PBSSAs and 537 PBFs), PBSSAs were less likely to receive drug-reduced ART, including 2-drug regimens and intermittent three-drug regimens (OR 0.48, 95% CI: 0.36 to 0.65). Differences in ART prescriptions between PBSSAs and PBFs were not only explained by different clinical and virologic situations. Personal motivations of doctors in choosing ART according to country of birth need to be explored.

Efecto de las emociones positivas post ejercicio como terapia complementaria en pacientes VIH/SIDA con tratamiento retroviral

Since the outbreak of the HIV pandemic, more than 30 million people have died from AIDS in the last 40 years; thus the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome (AIDS) continue to spread throughout the world. The effectiveness of retrovirals with modern drug combinations for the treatment of HIV/AIDS allows many people to improve their life expectancy. Although retrovirals have achieved a better quality of life among patients suffering from the disease, the disease can result in a number of adverse physical and physiological effects. In many cases, patients infected with the HIV/AIDS virus could be treated with other alternative forms adjunct to retroviral treatment such as physical exercises. The purpose of this research is to determine the effect of positive emotions generated after physical activity in various parks in the city of Lima as a complementary therapy in HIV/AIDS patients. For this, 25 patients divided into two groups were studied: a control of 10 people who was not under the exercise program, and a second group of 15 people who underwent an exercise regimen for one year. The experiments were analyzed using a Likert-type survey that measured participants' positive emotions and CD4 T-cell count. The results showed that people under the exercise regimen had a higher assessment of both positive emotions and CD4 T cells.

COVID-19 severity and in-hospital mortality in an area with high HIV prevalence.

HIV infection causes immune dysregulation affecting T-cell and monocyte function, which may alter coronavirus disease 2019 (COVID-19) pathophysiology. We investigated the associations among clinical phenotypes, laboratory biomarkers, and hospitalisation outcomes in a cohort of people hospitalised with COVID-19 in a high HIV prevalence area. We conducted a prospective observational cohort study in Tshwane, South Africa. Respiratory disease severity was quantified using the respiratory oxygenation score. Analysed biomarkers included inflammatory and coagulation biomarkers, CD4 T-cell counts, and HIV-1 viral loads (HIVVL). The analysis included 558 patients, of whom 21.7% died during admission. The mean age was 54 years. A total of 82 participants were HIV-positive. People living with HIV (PLWH) were younger (mean age 46 years) than HIV-negative people; most were on antiretroviral treatment with a suppressed HIVVL (72%) and the median CD4 count was 159 (interquartile range: 66-397) cells/µL. After adjusting for age, HIV was not associated with increased risk of mortality during hospitalisation (age-adjusted hazard ratio = 1.1, 95% confidence interval: 0.6-2.0). Inflammatory biomarker levels were similar in PLWH and HIV-negative patients. Detectable HIVVL was associated with less severe respiratory disease. In PLWH, mortality was associated with higher levels of inflammatory biomarkers. Opportunistic infections, and other risk factors for severe COVID-19, were common in PLWH who died. PLWH were not at increased risk of mortality and those with detectable HIVVL had less severe respiratory disease than those with suppressed HIVVL. This study advances our understanding of severe COVID-19 in PLWH.

HIV-1 Subtype C Vpr Amino Acid Residue 45Y and Specific Conserved Fragments Are Associated with Neurocognitive Impairment and Markers of Viral Load.

There is increasing evidence that HIV-1 viral protein R (Vpr) plays an important role in the pathogenesis of cognitive impairment. We investigated the relationship between HIV-1 subtype C Vpr sequence variation and HIV-associated neurocognitive impairment as measured by global deficit score (GDS) in treatment-naive individuals. We used different bioinformatic tools and statistical models to correlate vpr variation and cognitive function. We identified a tyrosine at position 45 (45Y) as a signature for neurocognitive impairment and histidine (45H) as a signature in the non-impaired individuals. The presence of signature 45Y was associated by 3.66 times higher GDS, 525 times higher plasma viral load, 15.84 times higher proviral load, and 60% lower absolute CD4-T cell count compared with those without the signature. Additionally, we identified four conserved Vpr fragment sequences, PEDQGPQREPYNEWTLE (5-21), LGQYIY (42-47), TYGDTW (49-54), and PEDQGPQREPYNEW (5-18), that were associated with higher plasma viral load and proviral load. The implication of these findings is that variation of Vpr leads to neurocognitive impairment in HIV infection and worsens the progression of disease in general by promoting the production of provirus, promoting HIV replication and depletion of CD4+ T cells in the periphery.

Assessment of Disease Burden and Immunization Rates for Vaccine-Preventable Diseases in People Living with HIV: The Korea HIV/AIDS Cohort Study.

Prophylactic immunization is important for human immunodeficiency virus (HIV)-infected patients; however, there are insufficient data on the burden of vaccine-preventable diseases (VPDs), vaccination rates, and factors influencing vaccination. The incidence and prevalence of VPDs in HIV-infected patients between 2006 and 2017 were estimated using the Korean HIV/acquired immune deficiency syndrome (AIDS) cohort database. In addition, we evaluated the vaccination rates and influencing factors for vaccination in HIV-infected patients through multilevel analysis of clinico-epidemiological factors, immune status, and psychological status. A questionnaire survey was conducted among experts to determine whether they recommend vaccination for HIV-infected patients. The incidence rates of hepatitis B virus (HBV) infection, herpes zoster, and anogenital warts were 1.74, 7.38, and 10.85 per 1,000 person-years, respectively. The prevalence of HBV infection and anogenital warts at enrollment was 4.8% and 8.6%, respectively, which increased to 5.3% and 12.0%, respectively, by 2017. In HIV-infected patients, HBV (21.7% in 2008, 56.3% in 2013, and 75.4% in 2017) and pneumococcal vaccination rates (3.0% in 2015, 7.6% in 2016, and 9.6% in 2017) increased annually, whereas the influenza vaccination rate remained similar by season (32.7 - 35.6%). In the multilevel analysis, peak HIV viral load (≥50 copies/mL: odds ratio [OR] = 0.64, 95% confidence interval [CI]: 0.44 - 0.93; reference, <50 copies/mL) was an influencing factor for pneumococcal vaccination, while nadir CD4 T-cell counts (200 - 350 cells/mm3: OR = 0.54, 95% CI: 0.38 - 0.76; <200 cells/mm3: OR = 0.89, 95% CI: 0.62 - 1.28; reference, ≥350 cells/mm3) was an influencing factor for HBV vaccination. Influenza vaccination was associated with male sex (OR = 1.94) and the number of antiretroviral therapy (ART) regimen change (OR = 1.16), but was not significantly associated with HIV viral load or CD4 T-cell counts. Most experts responded that they administer hepatitis A virus, HBV, pneumococcal, and influenza vaccines routinely, but not human papillomavirus (12.9%) or herpes zoster vaccines (27.1%). The burden of vaccine-preventable diseases was quite high in HIV-infected patients. Nadir CD4 T-cell counts, peak HIV viral loads, and the number of ART regimen change are significant factors related to vaccination. Considering the low vaccination rates for VPDs, there was a discordance between experts' opinions and real clinical practice in the medical field.

Diagnostic Value of Metagenomic Next-Generation Sequencing for Multi-Pathogenic Pneumonia in HIV-Infected Patients.

To evaluate the value and challenges of real-world clinical application of metagenomic next-generation sequencing (mNGS) for bronchoalveolar lavage fluid (BALF) in HIV-infected patients with suspected multi-pathogenic pneumonia. Fifty-seven HIV-infected patients with suspected mixed pneumonia who were agreed to undergo the bronchoscopy were recruited and retrospectively reviewed the results of mNGS and conventional microbiological tests (CMTs) of BALF from July 2020 to June 2022. 54 patients were diagnosed with pneumonia including 49 patients with definite pathogens and five patients with probable pathogens. mNGS exhibited a higher diagnostic accuracy for fungal detection than CMTs in HIV-infected patients with suspected pulmonary infection. The sensitivity of mNGS in diagnosis of pneumonia in HIV-infected patients was much higher than that of CMTs (79.6% vs 61.1%; P < 0.05). Patients with mixed infection had lower CD4 T-cell count and higher symptom duration before admitting to the hospital than those with single infection. The detection rate of mNGS for mixed infection was significantly higher than that of CMTs and more co-pathogens could be identified by mNGS. The most common pattern of mixed infection observed was fungi-virus (11/29, 37.9%), followed by fungi-virus-bacteria (6/29, 20.7%) coinfection in HIV-infected patients with multi-pathogenic pneumonia. mNGS improved the pathogens detection rate and exhibited advantages in identifying multi-pathogenic pneumonia in HIV-infected patients. Early performance of bronchoscopy and mNGS are recommended in HIV-infected patients with low CD4 T cell counts and long duration of symptoms. The most common pattern of mixed infection observed was fungi-virus, followed by fungi-virus-bacteria coinfection in HIV infected patients with multi-pathogenic pneumonia.

Hematological alterations associated with antiretroviral therapy in patients with human immunodeficiency virus

Introduction: hematological alterations are very frequent and of multifactorial origin, they have been related to an increased risk of pathology progression and morbimortality in patients infected by the human immunodeficiency virus. Although there is a wide variety of scientific studies on the prevalence and pathogenesis of these alterations in HIV-positive patients, there are few investigations in our environment that report on the positive or negative effect of the administration of antiretroviral drugs.Objective: to determine the main hematologic alterations associated with antiretroviral therapy in patients infected by the human immunodeficiency virus.Method: narrative bibliographic review. The following databases were used for the research: PubMed, Cochrane and Scopus. Results: the prevalence of at least one hematological alteration was 1,1-58,6 % among HIV-infected patients receiving ART. The most frequent cytopenia was anemia followed by leukopenia and thrombocytopenia. Among the most significant risk factors, patients older than 50 years, female sex, zidovudine-based antiretroviral regimen, low BMI and CD4 T-cell count, high viral load, advanced stage and opportunistic infections were identified.Conclusions: the toxicity of antiretroviral drugs and the clinical conditions of the HIV-positive patient result in altered hematopoiesis affecting all three cell lines, patients may present with anemia, leukopenia, thrombocytopenia and/or pancytopenia. Failure to monitor and identify these disorders has a serious impact on the natural history of the disease in the patient

Changing roles of CD3 + CD8 low T cells in combating HIV-1 infection.

Cluster of differentiation 8 (CD8 T) cells play critical roles in eradicating human immunodeficiency virus (HIV)-1 infection, but little is known about the effects of T cells expressing CD8 at low levels (CD8 low ) or high levels (CD8 high ) on HIV-1 replication inhibition after HIV-1 invasion into individual. Nineteen patients who had been acutely infected with HIV-1 (AHI) and 20 patients with chronic infection (CHI) for ≥2 years were enrolled in this study to investigate the dynamics of the quantity, activation, and immune responses of CD3 + CD8 low T cells and their counterpart CD3 + CD8 high T cells at different stages of HIV-1 infection. Compared with healthy donors, CD3 + CD8 low T cells expanded in HIV-1-infected individuals at different stages of infection. As HIV-1 infection progressed, CD3 + CD8 low T cells gradually decreased. Simultaneously, CD3 + CD8 high T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed. The classical activation of CD3 + CD8 low T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage. Meanwhile, activated CD38 - HLA-DR + CD8 low T cells did not increase in the first month of AHI, and the number of these cells was inversely associated with viral load ( r = -0.664, P = 0.004) but positively associated with the CD4 T-cell count ( r = 0.586, P = 0.014). Increased programmed cell death protein 1 (PD-1) abundance on CD3 + CD8 low T cells was observed from the 1st month of AHI but did not continue to be enhanced, while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) abundance increase was observed in the 12th month of infection. Furthermore, increased PD-1 and TIGIT abundance on CD3 + CD8 low T cells was associated with a low CD4 T-cell count (PD-1: r = -0.456, P = 0.043; TIGIT: r = -0.488, P = 0.029) in CHI. Nonetheless, the nonincrease in PD-1 expression on classically activated CD3 + CD8 low T cells was inversely associated with HIV-1 viremia in the first month of AHI ( r = -0.578, P = 0.015). Notably, in the first month of AHI, few CD3 + CD8 low T cells, but comparable amounts of CD3 + CD8 high T cells, responded to Gag peptides. Then, weaker HIV-1-specific T-cell responses were induced in CD3 + CD8 low T cells than CD3 + CD8 high T cells at the 3rd and 12th months of AHI and in CHI. Our findings suggest that CD3 + CD8 low T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response. Subsequently, CD3 + CD8 low T-cell number decreased gradually as infection persisted, and their anti-HIV functions were inferior to those of CD3 + CD8 high T cells.

Factors associated with reduced function and quality of life among adult people with HIV with depression and substance use in the Asia-Pacific region.

Depression and substance use (SU) disorders are prevalent among people with HIV (PWH) and impact health outcomes despite successful antiretroviral therapy (ART). We explored quality of life, functional ability and associated factors among PWH screened positive for depression and/or SU. This cross-sectional study recruited adult PWH during routine follow-up at five HIV clinical sites in the Asia-Pacific region. Participants were screened for depression using Patient Health Questionnaire-9 and SU using Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Quality of life (QoL) was assessed with WHOQOL-HIV BREF and functional ability with World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Factors associated with mean QoL and disability scores were analysed using linear regression. Of 864 PWH enrolled, 753 screened positive for depression or SU. The median (interquartile range, IQR) age was 38 (31-47) years and 97% were on ART. Overall mean WHOQOL-HIV BREF and WHODAS scores indicated greater impairment with increasing depressive symptom severity and SU risk. In multivariate analysis, PWH reporting previous trauma/stress (difference = 2.7, 95% confidence interval [CI] 1.5-3.9, P < 0.001) and past mental health diagnosis (difference = 5.0, 95% CI 2.9-7.1, P < 0.001) were associated with greater disability and poorer QoL scores across multiple domains ( P < 0.01 for all). Higher CD4 T-cell counts was also associated with better QoL scores and functional ability. PWH with depression/SU experienced poorer QoL and function despite routine engagement in HIV care. Efforts to integrate mental health services and interventions addressing disability into HIV management should be prioritized in the region.

Decrease in CD4 T-Cell Count and Risk of Severe Morbid Conditions in People With Human Immunodeficiency Virus Infection With Controlled Viral Load After Initiating Combination Antiretroviral Therapy Between 2006 and 2018.

A previous study showed an association between CD4 T-cell count decline in people with human immunodeficiency virus infection (PWH) with viral suppression and an increased risk of severe morbid conditions. We aimed to assess the risk of CD4 T-cell count decline (hereafter, CD4 decline), determine associated factors, and evaluate the association of this decline with the risk of severe morbid conditions (cardiovascular disease and cancer) or death. From the Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS) CO4 French Hospital Database on HIV cohort, we selected PWH >18 years old who had been followed up for ≥2 years after viral suppression following the initiation of combination antiretroviral therapy (cART) between 2006 and 2018. CD4 decline was defined as 2 consecutive relative differences ≥15%. Among participants with such decline, we modeled CD4, CD8, and total lymphocyte counts before and after CD4 decline, using spline regression. The remaining objectives were assessed using Poisson regression, with the association between CD4 decline and the risk of severe morbid conditions or death evaluated during or after 6 months of decline. Among 15 714 participants (75 417 person-years), 181 presented with CD4 decline (incidence rate, 2.4/1000 person-years (95% confidence interval, 2.1-2.8). CD8 and total lymphocyte counts also showed a similar decline. Older current age and lower viral load at treatment initiation were associated with the risk of CD4 decline. The risk of severe morbid conditions or death was 11-fold higher during the first 6 months for participants who presented with CD4 decline versus those who did not (incidence rate ratio, 10.8 [95% confidence interval, 5.1-22.8]), with no significant difference after 6 months. In PWH with viral suppression, CD4 decline was rare and related to global lymphopenia. It was associated with a higher risk of severe morbid conditions or death during the first 6 months.

2110. Immunocompromised Adults Hospitalized with Community-Acquired Pneumonia in the United States: Incidence and Clinical Outcomes

Abstract Background Community-acquired pneumonia (CAP) is an important complication in immunocompromised adults (ICAs). In hospitalized patients, the burden of CAP in ICAs is not well defined. The primary objective of this study was to define incidence, epidemiology, and outcomes of ICAs hospitalized with CAP in the city of Louisville. The secondary objective of this study was to estimate the burden of CAP in ICAs in the US. Methods This was a prospective population-based cohort study of consecutive hospitalized adult Louisville residents with CAP at all adult hospitals in Louisville from 1 June 2014 to 31 May 2016. An ICA was defined as a patient with any of the following medical conditions or treatments: (1) primary immunodeficiency disease; (2) advanced-stage cancer (stage III or IV cancer or hematologic cancer); (3) advanced HIV infection (CD4 T-lymphocyte count &amp;lt; 200 cells/mL or &amp;lt; 14%); (4) solid organ transplantation; (5) hematopoietic stem cell transplantation; (6) receiving cancer chemotherapy; (7) receiving biological immune modulators; (8) receiving corticosteroid therapy with a dose ≥ 20 mg prednisone or equivalent daily for at least 14 days prior to hospitalization; or (9) receiving disease-modifying antirheumatic drugs (DMARDs). The annual population-based CAP incidence among ICAs was calculated. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. Results A total of 7449 unique patients were included, with 854 (11%) ICAs identified. Figure 1 depicts the immunocompromising conditions. Per 100,000 adults in Louisville, each year 75 ICAs are hospitalized with CAP (95% CI: 68-78), corresponding to an estimated 190,106 ICAs hospitalized with CAP in the US. Mortality during hospitalization was 8% in ICAs vs 6% in non-ICAs; at 30 days 23% in ICAs vs 11% in non-ICAs, at 6 months 42% in ICAs vs 20% in non-ICAs, and at 1 year 52% in ICAs vs 27% in non-ICAs. Figure 1:Frequency of Immunocompromising Conditions and TreatmentsImmunocompromising conditions and treatments among 7449 patients hospitalized for community-acquired pneumonia sorted by frequency. Abbreviations: DMARDs: Disease-modifying antirheumatic drugs; HIV: Human immunodeficiency virus. Conclusion This study indicates that nearly one out of nine hospitalized CAP patients are immunocompromised, and 190,000 ICAs may be hospitalized due to CAP each year in the US. We found a twofold increase in mortality at every time point after discharge for ICAs compared to non-ICAs hospitalized due to CAP. Further strategies to prevent CAP and improve outcomes in ICAs hospitalized with CAP are necessary. Disclosures Forest W. Arnold, DO, MSc, Gilead Sciences, Inc.: Grant/Research Support.

1103. Virologic and Immunologic Outcomes in People Living with HIV in a Correctional Setting During the SARS-CoV-2 Pandemic

Abstract Background It is known that the pandemic increased the risk of severe illness from SARS-CoV-2 infection in immunocompromised patients as compared to the general public. To combat this issue, telemedicine was utilized in various settings, but there is very little data on the adequate continuity of care (COC) and sustainability of telehealth throughout the pandemic. There is even less data on the effects of the pandemic in special populations, such as people living with human immunodeficiency virus (PLWH) and within the correctional setting. The purpose of this study was to investigate rates of HIV virologic suppression (VS) and the sustainability of telemedicine throughout the SARS-CoV-2 pandemic. Methods This was a retrospective, pre-post cohort study of PLWH who received antiretroviral therapy (ART) within Illinois Department of Corrections (IDOC) / University of Illinois Chicago telemedicine clinic between 3/2019 and 3/2021. Patients who were released from IDOC or reincarcerated during the study period were excluded. The primary endpoint compared the rate of HIV VS pre-, peri- and post-SARS-CoV-2 restrictions. Secondary endpoints included change in immunologic function pre-, peri- and post-SARS-CoV-2 restrictions, incidence of SARS-CoV-2 infection, number of hospitalizations, development of virologic failure, and change in ART post-pandemic. Other factors known to influence COC were also collected. Results Of 320 patients screened, 225 were included. The majority were Black males (73.7%) and 95.1% had a CD4 T-cell count &amp;gt; 200 cells/mm3 at baseline. Approximately 88% of patients were on a single tablet regimen, with most receiving bictegravir/emtricitabine/tenofovir alafenamide. Rates of HIV VS are summarized in Figure 1 and secondary outcomes are summarized in table 1. Factors associated with disruption of COC included non-adherence to appointments (62.6%) and ART (4.4%). Figure 1Rates of HIV viral suppression (&amp;lt;200 copies/mL), n(%) Table 1 Secondary outcomes Conclusion Results demonstrated that PLWH within IDOC had sustained VS and COC throughout the SARS-CoV-2 pandemic with telemedicine. These results describe how the pandemic impacted PLWH in a correctional setting and future studies could contribute to creating national guidance for telemedicine models to streamline clinical practice. Disclosures All Authors: No reported disclosures.

796. HIV transmission clusters among people who inject drugs in North Carolina, 2010 to 2021

Abstract Background The marked increase in injecting drug use (IDU) in the past decade presents concern for increased HIV transmission among people who inject drugs (PWID) and explosive outbreaks. Among statewide HIV molecular surveillance, we assessed demographic, clinical, and reported behavioral risk factors associated with HIV clusters involving PWID in North Carolina (NC). Methods Persons ≥ 13 years old with HIV-infection residing in NC with ≥ 1 partial pol sequence collected between April 2010 and December 2021 were included in the study. We used an automated cluster analysis pipeline to detect genetic clusters (nextHIV2), defined as ≥ 2 sequences with a pairwise genetic distance &amp;lt; 1.5%. Logistic regression was used to estimate the risk and adjusted odds ratios of the relationship between the demographic factors that were likely associated with HIV clustering. Graphics were generated using the R packages ggplot2 and igraph. Results Among 19,641 persons with a sequence, 1,611 were PWID. Of these, 347 (21.5%) PWID were members of 248 clusters involving a total of 2,083 persons (size ranged 2–104). Sixty-four clusters (25%) had ≥2 PWID, whereas 2 (1%) included at least 5 PWID. The most commonly injected drug among cluster members was methamphetamine (19%). Overall, in a univariate analysis, younger age, dual risks of male-to-male sex and IDU, having sex under the influence of drugs, recent IDU (past 12 months), acute HIV infection, higher viral loads and higher CD4 T-cell count at the time of HIV diagnosis were significantly associated with clustering PWID individuals (all P&amp;lt; 0.001). In multivariate analyses, only recent IDU and higher CD4 T-cell count at the time of HIV diagnosis were significantly associated with clustering (P&amp;lt; 0.01). In addition, the proportion of PWID in clusters increased from 11.2% in 2010–2013 to 28.5% in 2018–2021 (P&amp;lt; 0.001). Nodes are colored by their reported PWID in darkred and reported non-PWID in blue. Conclusion We detected an increase in HIV genetic clusters among PWID in NC in recent years. Our results support the use of routine local molecular HIV surveillance to identify high priority clusters and offer prevention interventions for specific risk groups to prioritize limited public health resources. Disclosures Joseph J. Eron, MD, GSK: Advisor/Consultant|Merck: Advisor/Consultant.

Novel FujiLAM assay to detect tuberculosis in HIV-positive ambulatory patients in four African countries: a diagnostic accuracy study

Development of rapid biomarker-based tests that can diagnose tuberculosis using non-sputum samples is a priority for tuberculosis control. We aimed to compare the diagnostic accuracy of the novel Fujifilm SILVAMP TB LAM (FujiLAM) assay with the WHO-recommended Alere Determine TB-LAM Ag test (AlereLAM) using urine samples from HIV-positive patients. We did a diagnostic accuracy study at five outpatient public health facilities in Uganda, Kenya, Mozambique, and South Africa. Eligible patients were ambulatory HIV-positive individuals (aged ≥15 years) with symptoms of tuberculosis irrespective of their CD4 T-cell count (group 1), and asymptomatic patients with advanced HIV disease (CD4 count <200 cells per μL, or HIV clinical stage 3 or 4; group 2). All participants underwent clinical examination, chest x-ray, and blood sampling, and were requested to provide a fresh urine sample, and two sputum samples. FujiLAM and AlereLAM urine assays, Xpert MTB/RIF Ultra assay on sputum or urine, sputum culture for Mycobacterium tuberculosis, and CD4 count were systematically carried out for all patients. Sensitivity and specificity of FujiLAM and AlereLAM were evaluated against microbiological and composite reference standards. Between Aug 24, 2020 and Sept 21, 2021, 1575 patients (823 [52·3%] women) were included in the study: 1031 patients in group 1 and 544 patients in group 2. Tuberculosis was microbiologically confirmed in 96 (9·4%) of 1022 patients in group 1 and 18 (3·3%) of 542 patients in group 2. Using the microbiological reference standard, FujiLAM sensitivity was 60% (95% CI 51-69) and AlereLAM sensitivity was 40% (31-49; p<0·001). Among patients with CD4 counts of less than 200 cells per μL, FujiLAM sensitivity was 69% (57-79) and AlereLAM sensitivity was 52% (40-64; p=0·0218). Among patients with CD4 counts of 200 cells per μL or higher, FujiLAM sensitivity was 47% (34-61) and AlereLAM sensitivity was 24% (14-38; p=0·0116). Using the microbiological reference standard, FujiLAM specificity was 87% (95% CI 85-89) and AlereLAM specificity was 86% (95 CI 84-88; p=0·941). FujiLAM sensitivity varied by lot number from 48% (34-62) to 76% (57-89) and specificity from 77% (72-81) to 98% (93-99). Next-generation, higher sensitivity urine-lipoarabinomannan assays are potentially promising tests that allow rapid tuberculosis diagnosis at the point of care for HIV-positive patients. However, the variability in accuracy between FujiLAM lot numbers needs to be addressed before clinical use. ANRS and Médecins Sans Frontières.