Isolated Anti-HBc in People Living with HIV: A 20-Year Experience from Istanbul, Turkey.

Clinical impact of occult HBV infections

What Might Surviving Coronavirus Disease 2019 Look Like for People Living with HIV?

BackgroundRandomized and cohort studies from clinical practice have established the efficacy and tolerability of lamivudine/dolutegravir (3TC/DTG) in most people living with HIV (PLWH) with suppressed viral load. However, observations from...

Occult hepatitis B virus infection (OBI) is characterized by the absence of HBsAg and persistence of the virus genome (HBV-DNA) in liver tissue and/or blood. OBI has been reported in several clinical contexts. However, the clinical significance of OBI in tuberculosis (TB) treatment is unknown. We investigated the OBI prevalence and its impact on the risk of drug-induced liver injury (DILI) during TB treatment. This was a prospective cohort study with one hundred patients who were treated for TB from 2008 to 2015. Laboratory, clinical and demographic data of TB patients were extracted from medical records. Based on HBV-DNA testing of serum samples, an OBI prevalence of 12% was established; almost half of these patients had both anti-HBc and anti-HBs serological markers. Low CD4+ cell counts have been shown to be a risk factor for OBI among TB patients co-infected with HIV (P=.036). High DILI incidence was observed in this study. A multivariable Cox proportional hazard model was conducted and identified OBI (HR 2.98, 95% CI 1.30-6.86) as the strongest predictor for DILI when adjusted to CD4+ cell count (HR 0.38, 95% CI 0.17-0.90), ALT before TB treatment (HR 1.37, 95% CI 0.81-2.32) and TB extrapulmonary clinical form (HR 2.91, 95% CI 1.75-7.21). The main aim of this study was to highlight DILI as a clinical outcome during treatment of TB patients with OBI. Therefore, HBV-DNA testing should be considered routinely in monitoring DILI, and also in other clinical implications associated with OBI, reduce morbidity and mortality.

Factors Associated With Coronavirus Disease 2019 Morbidity in a Cohort of People Living With Human Immunodeficiency Virus.

BackgroundAlthough fatigue is a known symptom for people living with HIV (PWH) and a side effect of antiretroviral therapy (ART), its burden upon PWH is not well understood. We aimed to look at the impact of fatigue on quality of life (QoL) in PWH.MethodsData were drawn from the Adelphi Real World HIV Disease Specific Programme™, a cross-sectional survey, with retrospective data collection, of physicians and PWH in France, Germany, Italy, Spain, the United Kingdom and the United States from July 2021 – February 2024. Physicians reported demographics, clinical characteristics, fatigue as a side effect of ART and ART satisfaction for ten consecutively consulting PWH. PWH self-reported ART satisfaction, adherence via the Adelphi Adherence Questionnaire (ADAQ; scored 0–4, with 0 being perfect adherence) and QoL via PoZQoL (scored 0–5, with 5 being best QoL). Analyses were descriptive.ResultsOverall, 335 physicians reported on 3373 PWH, of whom 1008 self-reported data. Mean (standard deviation; SD) patient age was 42.8 (12.8) years and 72% were cisgender male.A total of 1913 PWH had no fatigue (NF) and 423 PWH had moderate to severe fatigue (MSF) due to ART. In total, 65% of MSF PWH were virally suppressed, 29% had no comorbidities and 32% had no side effects. For NF PWH, this was 81%, 54% and 87% of patients, respectively.Physicians were very satisfied with current ART for 78% of NF PWH compared to only 36% of MSF PWH. A total of 79% of physicians thought NF PWH were completely adherent compared to 48% for MSF PWH.Complete satisfaction with ART was reported by 63% of NF PWH compared to 31% of MSF PWH. Mean (SD) ADAQ scores were 0.2 (0.3) for NF PWH and 0.6 (0.6) for MSF PWH. Mean (SD) PozQoL scores were 3.6 (0.7) for NF PWH and 2.6 (0.7) for MSF PWH.ConclusionMSF was associated with low physician and PWH satisfaction with current ART, as well as low adherence and QoL scores. MSF PWH also commonly experienced comorbidities and treatment side effects, with fewer than half of PWH fully adherent to their treatment. Fatigue should be addressed as a prominent clinical burden in the treatment of PWH, with future research elucidating the link between fatigue severity and ART type.DisclosuresAll Authors: No reported disclosures

Delle Donne, Valentina MPsych, PhD; Massaroni, Valentina MPsych; Ciccarelli, Nicoletta MPsych, PhD; Lombardi, Francesca MBiol, PhD; Lamonica, Silvia MPharm; Borghetti, Alberto MD; Ciccullo, Arturo MD; Di Giambenedetto, Simona MD Author Information

Clonal hematopoiesis does not predict solid tumor malignancy in people living with HIV

BackgroundAll Chinese blood centers have implemented mini pool (MP) HBV nucleic acid testing (NAT) together with HBsAg ELISA in routine donor screening since 2015. The prevalence of occult hepatitis B virus infection (OBI) in donors from different regions varies, and the molecular characterization of the HBV DNA and clinical outcomes of these OBIs remain largely unexplored.MethodsBlood donations from Heyuan city in Southern China were screened by HBsAg ELISA and HBV MP8 NAT. Donations with HBsAg-/HBV DNA+ were collected for this study. Molecular characterizations of HBV DNAs were further analyzed by various DNA amplification assays including quantitative PCR (qPCR) and nested PCR, amplifying the basic core and pre-core promoter regions (BCP/PC). The HBsAg (S) region from HBV DNA was isolated by high-volume nucleic acid extraction. Notable mutations were identified by comparison to the HBV reference sequences. The clinical outcomes of the donors with OBIs were further followed for nearly 3 years.ResultsSeventy OBIs from 44,592 donations (0.15%) that we identified and reported previously were enrolled for this current study. HBV sequences were obtained from 44/70 OBIs, and genotyping analysis showed that 42/44 (95.2%) OBIs were genotype B, and 2/44 (4.8%) were genotype C. Interestingly, mutation analysis revealed that various mutations including M133L/T, F134L, P142L, V168A, R169H, S174N, L175S, and V177A of HBV DNA affecting HBsAg detection were observed in genotype B OBIs. Two notable mutations, T47K and L53S, were identified in genotype C OBIs. Follow-up studies showed that 3/31 (9.7%) OBIs converted to HBsAg+ as chronic infections while 1/31 (3.2%) HBV DNA was undetectable (classified as recovery) and 27/31 (87.1%) remained as OBIs.ConclusionVarious notable mutations affecting HBsAg detection were observed in blood donors with OBIs in Heyuan city of Southern China. Follow-up studies showed that most OBIs remained as OBIs with fluctuating or low viral loads. Higher sensitive HBV ID NAT is recommended for donor screening to further reduce the transmission risk of OBIs.

The natural history of occult hepatitis B virus infection (OBI) and the mechanism involved in HBV reactivation are only partially understood. As regards people living with HIV (PLWH), HBV reactivation is estimated to occur with an incidence ratio of 0.019 cases per 100 person-year. Here we report the case of OBI reactivation in a HIV/HCV co-infected patient followed for 25 years at our Infectious Diseases Unit, but, unfortunately, lost to follow-up about 19 months after Direct-acting antivirals (DAAs) treatment. At re-engagement, blood tests showed high replication of plasmatic HIV-RNA along with severe immunosuppression and normal levels of liver enzymes. However, 3 months after ART reintroduction, an immune reconstitution inflammatory syndrome (IRIS) was diagnosed with high detectable HBV-DNA load and transaminase elevation. Our case report shows how the balance between the virus and the host immune system is quite a dynamic process that might significantly impact the course of the disease. The aim of this case report is to bring to the attention of physicians that, although OBI reactivation is a rather rare occurrence, even amongst PLWH, its potential consequences compel to a high alertness on the matter. Therefore, especially in patients with an impaired immune system and on a tenofovir or lamivudine-sparing regimen, HBV serological and virological markers should always be strictly monitored, even in the absence of a hepatitis flare.

In recent decades, progress has been made worldwide in the prevention and control of HIV infection. What is the status of HIV prevention and control in China? This issue of HIV Medicine highlights the current progress in the management of and clinical research on HIV/AIDS in China, providing readers with a brief overview of this field. The Chinese authorities have made several efforts regarding the prevention and treatment of AIDS. For example, HIV infections transmitted by illegal blood transfusions have been eradicated, and HIV transmission among injecting drug users (IDUs) has been markedly reduced due to the implementation of a needle and syringe exchange programme. With the launch of the National Free Antiretroviral Treatment (ART) Program in 2003 and the subsequent implementation of the Four Free and One Care policy in 2006 [1], people living with HIV (PLWH) are often diagnosed via voluntary HIV testing or routine health examinations and provided free access to ART. The Four Free and One Care policy covers the provision of free ART to rural and urban residents without medical insurance; free voluntary counselling and HIV testing; free prevention of mother-to-child transmission; free schooling for orphaned children of PLWH; and care and economic assistance to PLWH with financial difficulties. In particular, the immediate initiation of ART in PLWH since 2016 has significantly reduced not only HIV transmission and prevalence but also AIDS-associated mortality [2]. Two studies in this issue analysed the clinical characteristics of patients receiving ART and pointed out the challenges faced by healthcare providers in China. Zhao et al. [3] presented the demographic and clinical characteristics of the national ART cohort for 2019. Their study showed great progress in increasing ART coverage and provided evidence of viral suppression across China. However, key populations of PLWH still face challenges: many are IDUs, have a history of treatment failure, or are co-infected with hepatitis C virus. Liu et al. [4] analysed the barriers to early diagnosis and timely ART initiation among PLWH, and their findings indicate the need for additional screening and intervention to improve the clinical management of HIV/AIDS. Co-infection with other viruses and bacteria among PLWH is associated with an increased incidence of failed immune reconstitution during ART and leads to a mortality rate higher than that associated with HIV infection alone. Two papers highlighted coinfections with hepatitis B virus (HBV) and Mycobacterium tuberculosis in PLWH. Jiang et al. [5] examined the factors associated with immune reconstitution in individuals with HIV/HBV co-infection receiving ART. They found that the baseline HIV viral load was the only significant factor that negatively influenced CD4 T-cell restoration in this population. Qi et al. [6] investigated tuberculosis (TB)-associated mortality within 90 days of admission and its risk factors among PLWH. Their data showed the 90-day mortality rate in patients with co-infection to be 13.6%, and early TB-associated death was associated with central nervous system TB, not receiving ART within 3 months after admission, and serum albumin levels < 25 g/L. In the era of ART, mother-to-child HIV transmission has substantially decreased. However, anti-HIV antibodies may still be detected in uninfected infants of mothers with chronic HIV infection. On monitoring the dynamics of anti-HIV antibodies in these infants, Liu et al. [7] noted the clearance of anti-HIV antibodies at more than 18 months post-delivery in 5.8% of uninfected children. These findings indicate that positive results for anti-HIV antibodies in infants aged 18–24 months should be carefully interpreted. Simultaneously, additional nucleic acid tests are necessary to confirm a diagnosis of HIV infection. Although ART has increased the life expectancy and improved the quality of life of PLWH, non-AIDS-associated events remain an issue. Lin et al. [8] summarized the clinical characteristics of non-AIDS-associated events involving multiple organs, such as the liver and kidneys, and suggested that multidisciplinary management is necessary for PLWH. Ying et al. [9] investigated the epidemiology, clinical features, and prognostic factors of HIV-associated talaromycosis and found an increased prevalence in Guangdong, China. Typical skin lesions were noted in 44.5% of patients. Induction therapy with azole alone was associated with a higher mortality than therapy with amphotericin B deoxycholate. These results may serve as a guide for clinicians in the management of HIV-associated talaromycosis. The viral reservoir is the biggest hurdle in the race to cure HIV/AIDS. In the shock and kill strategy, the latent HIV reservoir is maximally activated by stimulation with latency reversal agents and further cleared by host immune surveillance. Li et al. [10] evaluated the safety and efficacy of chidamide, a histone deacetylase inhibitor, for HIV-1 latency reversal in seven participants with viral suppression. All participants exhibited robust and repeated plasma viral rebound and increased cell-associated HIV-1 RNA levels, but only grade 1 adverse events were reported. Chidamide seems to be an effective agent in disrupting HIV-1 latency and reducing HIV-1 DNA loads; however, these findings need to be confirmed in randomized controlled clinical trials. Zhang et al. [11] summarized recent findings regarding the role of CD8 T-cells in controlling HIV infection, highlighting the differences between conventional antigen-specific and innate-like CD8 T-cells. Antiviral activity of CD8 T-cells in PLWH receiving ART may not be achieved via an antigen-specific approach, as HIV-specific CD8 T-cells can sense, but not effectively eliminate, cells harbouring intact proviruses. By contrast, virtual memory CD8 T-cells, a semi-differentiated subset of CD8 T-cells, may be involved in controlling the HIV DNA reservoir in patients receiving ART. In China, although remarkable progress has been made in controlling the HIV epidemic, challenges remain. First, the absolute number of PLWH is approximately 1.2 million, and the annual number of newly identified HIV/AIDS cases has been determined to be 150 000 in the last 3 years. In particular, approximately 31% of PLWH were diagnosed in the advanced stage, with peripheral CD4 T-cell counts of less than 200 cells/µL [3, 12]. In-time HIV screening is necessary to identify PLWH at an early stage. Second, the choice of ART drugs for PLWH is limited; for example, integrase inhibitors have recently been included in the free ART regimen, but this programme does not cover all PLWH. Third, sexual transmission has become the main route of HIV spread, and such transmission needs to be reduced by efficient preventive programmes, such as those providing universal pre-exposure prophylaxis. The 90-90-90 goals put forth by the Joint United Nations Program on AIDS/HIV seek for 90% of PLWH to be diagnosed, 90% of those diagnosed to receive ART, and 90% of those receiving ART to show viral suppression. It is feasible to achieve these 90-90-90 goals during next 5 years in China, but we still have a long way to go for the development of a cure for HIV infection.

Fibroblast Growth Factor 21 Is Elevated in HIV and Associated With Interleukin-6.

Cross-sectional investigation of pneumococcal vaccination patterns in HIV patients at a tertiary care hospital in Riyadh, Saudi Arabia.

Background The WHO estimated that in 2022 49% of people affected by Mpox were PLWH. Due to initial vaccine shortage in 2022, a 1/5 dose of vaccine given intradermally (ID) was FDA-authorized (8/9/22). The ID regimen had never been evaluated in PLWH. Here we describe the characteristics, and IgG responses of Mpox vaccination in PLWH and HIV-negative participants. Methods We are conducting a longitudinal, observational study of adults with and without HIV who received the JYNNEOS vaccine or had Mpox infection in NYC. Clinical, demographic information, and Mpox H3L-specific serum IgG titers are assessed. Results 145 participants are enrolled: 25% are PLWH (median CD4 685 cells/mm3), 14% had Mpox disease and 21% had prior smallpox vaccination. 71% with Mpox disease were PLWH. The cohort is racially/ethnically diverse, mostly men (81%) and LGBTQ+ (90%). A third of the participants were recruited from NYC DOHMH pop-up vaccination site (34%), followed by peer or professional referral (20% &amp; 19%). Routes of vaccination were: SC-ID (49%), ID-ID (21%), SC-SC (20%), and ID-SC (10%). Redness (37%) &amp; swelling (21%) at site of injection were common reactions. Prior smallpox vaccination was associated with higher and sustained IgG titers even after one vaccine dose. Excluding such participants, antibody titers start declining post-dose 2 (antibody half-life of 103 days). There was no difference in IgG titers at 3 months post-dose 2 between PLWH and HIV-negative for ID or any other route. Titers at 3 months post-dose 2 in PLWH correlated with CD4 counts. Longer interval between the two doses contributed to higher titers. Mpox infection yielded to significantly higher titers than vaccination post-dose 1, but no after 2 doses. Conclusion Our study highlights the disproportionate burden of Mpox infection on PLWH. A diverse population representative of those most affected by 2022 Mpox was recruited. The vaccine, whether ID or SC, was well tolerated in PLWH and HIV-negative. More than two-thirds of participants with Mpox disease were PLWH. Individuals with prior smallpox vaccination maintain strong antibody levels post-dose 2, however, levels decline in individuals with no anterior prime. Our preliminary results show no negative impact of the ID dose regimen on antibody levels in PLWH. Disclosures Ellie Carmody, MD, MPH, AstraZeneca: Stocks/Bonds|Merck: Stocks/Bonds Lalitha Parameswaran, MD, MPH, Pfizer: Grant/Research Support Mark J. Mulligan, M.D., Lilly: Grant/Research Support|Meissa Vaccines, Inc.: Advisor/Consultant|Meissa Vaccines, Inc.: Board Member|Merck: Advisor/Consultant|Merck: Board Member|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support

BackgroundAlthough the introduction of antiretroviral therapy (ART) decreased the mortality of people living with Human Immunodeficiency Virus (PLHIV), substantially, hundreds of thousands of people are dying of AIDS each year. The accurate survival patterns and factors related to death among PLHIV were rarely reported. In this study, we evaluated survival status and identified factors associated with death among PLHIV in Nanjing.MethodsWe conducted a retrospective analysis of PLHIV followed-up in Nanjing and registered to the national HIV/AIDS comprehensive management information system from 2005 to 2018. We used the life table to calculate the cumulative survival rates. We applied the Kaplan-Meier to calculate median survival times and employed cox hazard proportional regression to analyze the associated factors related to death.ResultsThe median survival time of PLHIV was 11.8 (95%CI:11.6–11.9) years from 2005 to 2018. Among 4,235 PLHIV included in this study, 7.5% had died of AIDS-related disease and the AIDS-related mortality rate was 2.0/100 PYs. The cumulative proportion surviving at the end of the interval was 95.2% over the 1st year, 94.0% over the 2nd year, 91.8% over the 5th year, and 85.4% over the 10th year, respectively. PLHIV who unaccepted ART showed a greater risk of death compared to those who accepted ART (AHR = 16.2, 95%CI:11.9~22.2). For baseline CD4 count, compared to CD4 < 200 cell/μL, higher CD4 count was demonstrated as a protective factor, with AHR = 0.2 (95%CI: 0.1~0.3) for ≥500 cell/μL, AHR = 0.3 (95%CI:0.2~0.4) for 350~499 cell/μL, AHR = 0.4 (95%CI:0.3~0.6 for 200~349 cell/μL). In addition, we observed a higher death risk in PLHIV who were screened through outpatient (AHR = 1.6, 95%CI: 1.1~2.2) and inpatient (AHR = 1.6, 95%CI: 1.1~2.5) compared to through VCT; the age of diagnosis was ≥50 years old (AHR = 9.5, 95%CI: 3.7~24.1) and 25~49 years old (AHR = 5.0, 95%CI: 2.0~12.3) compared to ≤ 24 years old; educated from junior and below (AHR = 3.4, 95%CI: 2.3~5.1) and Senior high school (AHR = 1.7, 95%CI: 1.1~2.7) compared to college and above.ConclusionThe AIDS-related mortality among PLHIV in Nanjing was relatively low. A higher risk for AIDS-related deaths were observed among PLHIV who unaccepted ART, whose baseline CD4 cell count was<200 cell/μL, older age, and lower educated.