Development and management of systemic lupus erythematosus in an HIV-infected man with hepatitis C and B co-infection following interferon therapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>The association of human immunodeficiency virus and immune dysfunction leading to development of autoimmune markers is well described, but human immunodeficiency virus infection is relatively protective for the development of systemic lupus erythematosus. In contrast, development of systemic lupus erythematosus with hepatitis C and with interferon therapy is well described in a number of case reports. We here describe the first case of systemic lupus erythematosus developing in a man infected with human immunodeficiency virus, hepatitis C and hepatitis B co-infection where the onset seems to have been temporally related to interferon therapy.</p> <p>Case presentation</p> <p>We report the occurrence of systemic lupus erythematosus complicating interferon-α therapy for hepatitis C in a 47-year-old asplenic male with haemophilia co-infected with human immunodeficiency virus and hepatitis B. He presented with a truncal rash, abdominal pains and headache and later developed grade IV lupus nephritis requiring haemodialysis, mycophenolate mofetil and steroid therapy. We were able to successfully withdraw dialysis and mycophenolate while maintaining stable renal function.</p> <p>Conclusion</p> <p>Interferon-α is critical in antiviral immunity against hepatitis C but also acts as a pathogenic mediator for systemic lupus erythematosus, a condition associated with activation of plasmacytoid dendritic cells that are depleted in human immunodeficiency virus infection. The occurrence of auto-antibodies and lupus-like features in the coinfections with hepatitis C require careful assessment. Immunosuppressant therapy for lupus risks exacerbating underlying infections in patients with concurrent human immunodeficiency virus, hepatitis B and C.</p

Mpox (monkeypox) knowledge, concern, willingness to change behaviour, and seek vaccination: results of a national cross-sectional survey.

BACKGROUND: In mid-2022, a global mpox (formerly 'monkeypox') outbreak affecting predominantly gay and bisexual men emerged in non-endemic countries. Australia had never previously recorded mpox cases and there was no prior research on knowledge or attitudes to mpox among gay and bisexual men across Australia. METHODS: We conducted a national, online cross-sectional survey between August 2022 and September 2022. Participants were recruited through community organisation promotions, online advertising, and direct email invitations. Eligible participants were gay, bisexual or queer; identified as male (cisgender or transgender) or non-binary; aged 16years or older; and lived in Australia. The main outcome measures were: knowledge and concern about mpox; recognition of mpox symptoms and transmission routes; vaccination history; acceptability of behavioural changes to reduce mpox risk, and willingness to be vaccinated. RESULTS: Of 2287 participants, most participants were male (2189/2287; 95.7%) and gay (1894/2287; 82.8%). Nearly all had heard about mpox (2255/2287; 98.6%), and the majority were concerned about acquiring it (1461/2287; 64.4%). Most of the 2268 participants not previously diagnosed with mpox correctly identified skin lesions (2087; 92%), rash (1977; 87.2%), and fever (1647; 72.6%) as potential symptoms, and prolonged and brief skin-to-skin contact as potential ways to acquire mpox (2124, 93.7%; and 1860, 82%, respectively). The most acceptable behavioural changes were reducing or avoiding attendance at sex parties (1494; 65.9%) and sex-on-premises venues (1503; 66.4%), and having fewer sexual partners (1466; 64.6%). Most unvaccinated and undiagnosed participants were willing to be vaccinated (1457/1733; 84.1%). CONCLUSIONS: People at risk of mpox should be supported to adopt acceptable risk reduction strategies during outbreaks and to seek vaccination

Duffy-Null–Associated Low Neutrophil Counts Influence HIV-1 Susceptibility in High-Risk South African Black Women.

Background. The Duffy-null trait and ethnic netropenia are both highly prevalent in Africa. The influence of pre-seroconversion levels of peripheral blood cell counts (PBCs) on the risk of acquiring human immunodeficiency virus (HIV)–1 infection among Africans is unknown. Methods. The triangular relationship among pre-seroconversion PBC counts, host genotypes, and risk of HIV acquisition was determined in a prospective cohort of black South African high-risk female sex workers. Twenty seven women had seroconversion during follow-up, and 115 remained HIV negative for 2 years, despite engaging in high-risk activity. Results. Pre-seroconversion neutrophil counts in women who subsequently had seroconversion were significantly lower, whereas platelet counts were higher, compared with those who remained HIV negative. Comprising 27% of the cohort, subjects with pre-seroconversion neutrophil counts of C) was significantly associated with neutrophil counts (P = 7.9 x10-11). DARC -46C/C results in loss of DARC expression on erthyrocytes (Duffy-null) and resistance to Plasmodium vivax malaria, and in our cohort, only subjects with this genotype had pre-seroconversion neutrophil counts of <2500 cells/mm3. The risk of acquiring HIV infection was ~3-fold greater in those with the trait of Duffy-null–associated low neutrophil counts, compared with all other study participants. Conclusions. Pre-seroconversion neutrophil and platelet counts influence risk of HIV infection. The trait of Duffy-null–associated low neutrophil counts influences HIV susceptibility. Because of the high prevalence of this trait among persons of African ancestry, it may contribute to the dynamics of the HIV epidemic in Africa

MicroRNA-218 Is Deleted and Downregulated in Lung Squamous Cell Carcinoma

MicroRNAs (miRNAs) are a family of small, non-coding RNA species functioning as negative regulators of multiple target genes including tumour suppressor genes and oncogenes. Many miRNA gene loci are located within cancer-associated genomic regions. To identify potential new amplified oncogenic and/or deleted tumour suppressing miRNAs in lung cancer, we inferred miRNA gene dosage from high dimensional arrayCGH data. From miRBase v9.0 (http://microrna.sanger.ac.uk), 474 human miRNA genes were physically mapped to regions of chromosomal loss or gain identified from a high-resolution genome-wide arrayCGH study of 132 primary non-small cell lung cancers (NSCLCs) (a training set of 60 squamous cell carcinomas and 72 adenocarcinomas). MiRNAs were selected as candidates if their immediately flanking probes or host gene were deleted or amplified in at least 25% of primary tumours using both Analysis of Copy Errors algorithm and fold change (≥±1.2) analyses. Using these criteria, 97 miRNAs mapped to regions of aberrant copy number. Analysis of three independent published lung cancer arrayCGH datasets confirmed that 22 of these miRNA loci showed directionally concordant copy number variation. MiR-218, encoded on 4p15.31 and 5q35.1 within two host genes (SLIT2 and SLIT3), in a region of copy number loss, was selected as a priority candidate for follow-up as it is reported as underexpressed in lung cancer. We confirmed decreased expression of mature miR-218 and its host genes by qRT-PCR in 39 NSCLCs relative to normal lung tissue. This downregulation of miR-218 was found to be associated with a history of cigarette smoking, but not human papilloma virus. Thus, we show for the first time that putative lung cancer-associated miRNAs can be identified from genome-wide arrayCGH datasets using a bioinformatics mapping approach, and report that miR-218 is a strong candidate tumour suppressing miRNA potentially involved in lung cancer

Array-Comparative Genomic Hybridization Reveals Loss of SOCS6 Is Associated with Poor Prognosis in Primary Lung Squamous Cell Carcinoma

BACKGROUND: Primary tumor recurrence commonly occurs after surgical resection of lung squamous cell carcinoma (SCC). Little is known about the genes driving SCC recurrence. METHODS: We used array comparative genomic hybridization (aCGH) to identify genes affected by copy number alterations that may be involved in SCC recurrence. Training and test sets of resected primary lung SCC were assembled. aCGH was used to determine genomic copy number in a training set of 62 primary lung SCCs (28 with recurrence and 34 with no evidence of recurrence) and the altered copy number of candidate genes was confirmed by quantitative PCR (qPCR). An independent test set of 72 primary lung SCCs (20 with recurrence and 52 with no evidence of recurrence) was used for biological validation. mRNA expression of candidate genes was studied using qRT-PCR. Candidate gene promoter methylation was evaluated using methylation microarrays and Sequenom EpiTYPER analysis. RESULTS: 18q22.3 loss was identified by aCGH as being significantly associated with recurrence (p = 0.038). Seven genes within 18q22.3 had aCGH copy number loss associated with recurrence but only SOCS6 copy number was both technically replicated by qPCR and biologically validated in the test set. SOCS6 copy number loss correlated with reduced mRNA expression in the study samples and in the samples with copy number loss, there was a trend for increased methylation, albeit non-significant. Overall survival was significantly poorer in patients with SOCS6 loss compared to patients without SOCS6 loss in both the training (30 vs. 43 months, p = 0.023) and test set (27 vs. 43 months, p = 0.010). CONCLUSION: Reduced copy number and mRNA expression of SOCS6 are associated with disease recurrence in primary lung SCC and may be useful prognostic biomarkers

Antiretroviral initiation at ≥800 CD4+ cells/ mm 3 associated with lower HIV reservoir size.

BACKGROUND: Identifying factors that determine the frequency of latently infected CD4+ T-cells on antiretroviral therapy (ART) may inform strategies for HIV cure. We investigated the role of CD4 count at ART initiation for HIV persistence on ART. METHODS: Among participants of the Strategic Timing of Antiretroviral Treatment (START) Study, we enrolled people with HIV (PWH) who initiated ART with CD4+ T-cell counts of 500-599, 600-799 or ≥800 cells/mm 3. After 36-44 months on ART, we quantified levels of total HIV-DNA, cell-associated unspliced HIV-RNA (CA-US HIV-RNA) and 2-long terminal repeat HIV-DNA in CD4+ T-cells and measured plasma HIV-RNA by single-copy assay. We measured T-cell expression of HLA-DR, programmed death-1, phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+ strata. RESULTS: We enrolled 146 PWH, 36 in the 500-599, 60 in the 600-799 and 50 in the ≥800 CD4 strata. After 36-44 months of ART, total HIV-DNA, plasma HIV-RNA and HLA-DR expression were significantly lower in PWH with CD4+ T-cell count ≥800 cells/mm 3 at ART initiation compared to 600-799 or 500-599 cells/mm 3. The median level of HIV-DNA after 36-44 months of ART was lower by 75% in participants initiating ART with ≥800 vs. 500-599 cells/mm 3 [median (IQR): 16.3 (7.0-117.6) vs. 68.4 (13.7-213.1) copies/million cells, respectively). Higher pSTAT5 expression significantly correlated with lower levels of HIV-DNA and CA-US HIV-RNA. Virological measures were significantly lower in females.. CONCLUSION: Initiating ART with a CD4+ count ≥800 cells/mm 3 compared to 600-799 or 500-599 cells/mm 3 was associated with achieving a substantially smaller HIV reservoir on ART