Mycobacterium tuberculosis resisters despite HIV exhibit activated T cells and macrophages in their pulmonary alveoli.

To understand natural resistance to Mycobacterium tuberculosis ( Mtb ) infection, we studied people living with HIV (PLWH) in an area of high Mtb transmission. Given that alveolar leukocytes may contribute to this resistance, we performed single cell RNA-sequencing of bronchoalveolar lavage cells, unstimulated or ex vivo stimulated with Mtb . We obtained high quality cells for 7 participants who were TST & IGRA positive (called LTBI) and 6 who were persistently TST & IGRA negative (called resisters). Alveolar macrophages (AM) from resisters displayed more of an M1 phenotype relative to LTBI AM at baseline. Alveolar lymphocytosis (10%-60%) was exhibited by 5/6 resisters, resulting in higher numbers of CD4 + and CD8 + IFNG -expressing cells at baseline and upon Mtb challenge than LTBI samples. Mycobactericidal granulysin was expressed almost exclusively by a cluster of CD8 + T cells that co-expressed granzyme B, perforin and NK cell receptors. For resisters, these poly-cytotoxic T cells over-represented activating NK cell receptors and were present at 15-fold higher numbers in alveoli compared to LTBI. Altogether, our results showed that alveolar lymphocytosis, with increased numbers of alveolar IFNG -expressing cells and CD8 + poly-cytotoxic T cells, as well as activated AM were strongly associated with protection from persistent Mtb infection in PLWH.

Use and acceptability of salivary hepatitis C virus testing in an English Young Offender Institution.

People held in prison are at a high risk of having hepatitis C virus (HCV) and there is a public health drive in the UK to increase HCV testing in prisons and Young Offender Institutions (YOIs), with opt-out testing. There is an oral antibody test for HCV; this project aims to determine its acceptability in an English YOI setting. This project offered HCV oral point-of-care testing (POCT) using the OraQuick® test to 107 male young offenders attending a sexual health service at an English YOI, monitoring HCV positivity and evaluating acceptability. It also investigated young offenders' histories of sexually transmitted infections (STIs) and drug use. Mean age was 19.1 years. A total of 80.4% reported lifetime drug use and 0.9% reported lifetime drug injection. A total of 19.6% reported previous STIs. One patient (0.9%) was positive for HCV on OraQuick® testing. All patients found the POCT acceptable and one stated he would have refused a fingerprick test had it been the only test available for HCV testing. Salivary rapid HCV testing is acceptable among English YOI inmates. It is not as sensitive or specific as standard HCV tests and is more expensive. In our cohort, HCV positivity was low.

Herpes simplex virus type 2 (HSV-2) seroprevalence at the time of HIV-1 diagnosis and seroincidence after HIV-1 diagnosis in an ethnically diverse cohort of HIV-1-infected persons.

OBJECTIVE: The objective of this study was to determine herpes simplex virus type 2 (HSV-2) seroprevalence at HIV-1 diagnosis and seroincidence > or =1 year after HIV-1 diagnosis. METHODS: HSV type-specific antibodies were detected by enzyme immunoassay. RESULTS: The cohort comprised 850 adults diagnosed HIV-positive in 1986-2001 and followed for a median of 3 years. HSV-2 seroprevalence was 63% (95% confidence interval [CI], 60-66%) and was associated with female gender, heterosexual risk group, black ethnicity, and older age. HSV-2 seroincidence was 1.8 per 100 person-years (95% CI, 0.8-2.8) and was associated with other sexually transmitted diseases, including human papilloma virus infection (P = 0.005) and gonorrhea (P = 0.05). A diagnosis of genital herpes was made in 21% HSV-2-seropositive persons and was more likely in those who tested HIV-positive before 1997 (adjusted odds ratio, 5.11; 95% CI, 3.28-7.98; P = 0.0001). CONCLUSIONS: Results confirm the epidemiologic association between HIV-1 and HSV-2. HSV-2 seroconversion was a marker of high-risk sexual behavior. The likelihood of developing symptoms of genital herpes declined from 1997 onward.