Nneka Nwokolo

Rectal chlamydia - a reservoir of undiagnosed infection in men who have sex with men.

Objective: To determine the prevalence of rectal chlamydia infection in a cohort of men who have sex with men (MSM) and the proportion of infection that would be missed without routine screening. Methods: MSM presenting to four HIV/GUM outpatient clinics at the Chelsea & Westminster Hospital NHS Foundation Trust between 1 November 2005 and 29 September 2006 were offered testing for rectal chlamydia infection in addition to their routine screen for sexually transmitted infections (STIs). Chlamydia trachomatis (CT) tests were performed using the Beckton-Dickinson Probe-Tec Strand Displacement Assay. Positive samples were re-tested at the Sexually Transmitted Bacteria Reference Laboratory, to confirm the result and identify lymphogranuloma venereum (LGV)-associated serovars. Results: A total of 3076 men were screened. We found an 8.2% prevalence of infection with CT (LGV and non-LGV serovars) in the rectum and 5.4% in the urethra. The HIV and rectal chlamydia co-infection rate was 38.1%. The majority of rectal infections (69.2%, (171/247)) were asymptomatic and would have been missed if routine screening had not been undertaken. Of the samples re-tested, 94.2% (227/242) rectal and 91.8% (79/86) urethral specimens were confirmed CT positive and 36 cases of LGV were identified. Conclusion: Our data show a high rate of rectal chlamydia infection, in the majority of cases it was asymptomatic. We recommend routine screening for rectal chlamydia in men at risk, as this may represent an important reservoir for the onward transmission of infection.

2015 UK national guideline for the management of infection with Chlamydia trachomatis

This guideline offers recommendations on the diagnostic tests, treatment regimens and health promotion principles needed for the effective management of Chlamydia trachomatis genital infection. It covers the management of the initial presentation, as well the prevention of transmission and future infection. The guideline is aimed at individuals aged 16 years and older presenting to healthcare professionals working in departments offering Level 3 care in sexually transmitted infections management within the UK. However, the principles of the recommendations should be adopted across all levels, using local care pathways where appropriate.

Poly drug use, chemsex drug use, and associations with sexual risk behaviour in HIV-negative men who have sex with men attending sexual health clinics

BACKGROUND Recreational drug use and associated harms continue to be of significant concern in men who have sex with men (MSM) particularly in the context of HIV and STI transmission. METHODS Data from 1484 HIV-negative or undiagnosed MSM included in the AURAH study, a cross-sectional, self-completed questionnaire study of 2630 individuals from 20 sexual health clinics in the United Kingdom in 2013-2014, was analysed. Two measures of recreational drug use in the previous three months were defined; (i) polydrug use (use of 3 or more recreational drugs) and (ii) chemsex drug use (use of mephedrone, crystal methamphetamine or GHB/GBL). Associations of socio-demographic, health and lifestyle factors with drug use, and associations of drug use with sexual behaviour, were investigated. RESULTS Of the 1484 MSM, 350 (23.6%) reported polydrug use and 324 (21.8%) reported chemsex drug use in the past three months. Overall 852 (57.5%) men reported condomless sex in the past three months; 430 (29.0%) had CLS with ≥2 partners, 474 (31.9%) had CLS with unknown/HIV+ partner(s); 187 (12.6%) had receptive CLS with an unknown status partner. For polydrug use, prevalence ratios (95% confidence interval) for association with CLS measures, adjusted for socio-demographic factors were: 1.38 (1.26, 1.51) for CLS; 2.11 (1.80, 2.47) for CLS with ≥2 partners; 1.89 (1.63, 2.19) for CLS with unknown/HIV+ partner(s); 1.36 (1.00, 1.83) for receptive CLS with an unknown status partner. Corresponding adjusted prevalence ratios for chemsex drug use were: 1.38 (1.26, 1.52); 2.07 (1.76, 2.43); 1.88 (1.62, 2.19); 1.49 (1.10, 2.02). Polydrug and chemsex drug use were also strongly associated with previous STI, PEP use, group sex and high number of new sexual partners. Associations remained with little attenuation after further adjustment for depressive symptoms and alcohol intake. CONCLUSION There was a high prevalence of polydrug use and chemsex drug use among HIV negative MSM attending UK sexual health clinics. Drug use was strongly associated with sexual behaviours linked to risk of acquisition of STIs and HIV.

Exhaustion of Activated CD8 T Cells Predicts Disease Progression in Primary HIV-1 Infection.

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n = 122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression. Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed. Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants. Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches.

Cessation of secondary prophylaxis in patients with cryptococcosis.

: Cryptococcal disease in HIV-positive individuals is usually a consequence of advanced immunosuppression. Treatment consists of long period of induction therapy followed by long-term secondary prophylaxis, usually with fluconazole. The introduction of highly active antiretroviral therapy has resulted in improvements in immunological function such that the cessation of primary and secondary prophylaxis against several opportunistic infections has become possible. We report our experience of the cessation of secondary antifungal prophylaxis in patients responding to highly active antiretroviral therapy.

Diagnostics within the clinic to test for gonorrhoea and chlamydia reduces the time to treatment: a service evaluation

Rapid on-site diagnostics permit prompt recognition and treatment of infections. We introduced the GeneXpert system (Cepheid, California, USA) within 56 Dean Street, a central London sexual health clinic. The machine processes Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) samples in 90 min by real-time PCR. We present the results of the service evaluation of a pilot where GeneXpert was used to process samples from individuals attending outreach or specialised clinics. Asymptomatic attenders whose samples were processed using the GeneXpert system were compared with asymptomatic ‘standard of care’ …

Protein and creatine supplements and misdiagnosis of kidney disease

Check dietary supplement history before investigating apparently declining renal function

Rapidly declining HIV infection in MSM in central London

In 2016, there were 1·8 million new HIV infections worldwide. Although the annual number of new HIV infections has fallen by 16% since 2010, the rate of decline is far too slow to meet the fast-track target of 500 000 new infections per year, agreed at the UN General Assembly in 2016. We still have no cure or effective vaccine to prevent HIV. There are, however, many HIV prevention approaches available, including rapid treatment of those diagnosed with HIV to render them uninfectious— the treatment as prevention strategy. This has been an important UNAIDS policy to diminish the global burden of HIV by achieving the 90-90-90 metric by 2020 and embraced by the fast-track cities campaign. In some countries where 90-90-90 has been or has almost been achieved, incidence rates have not declined meaningfully, but in others such as Swaziland, where there is a comprehensive test-and-treat programme linked to prevention including voluntary medical male circumcision, incidence has fallen by 44%. Until 2015, new HIV infections in the UK were relatively stable, with a total of 6286 infections in that year. In 2016, Public Health England reported an 18% reduction in new diagnoses, with a 21% decrease among gay and bisexual men, a group in whom diagnoses had steadily been increasing since 2007. The reduced incidence in gay and bisexual men was most pronounced in London, in whom there was a 29% decrease with an overall decline in infections in gay men outside London of 11%. The accepted explanation for this significant change was a large increase in HIV tests among gay and bisexual men attending sexual health clinics (from 37 224 in 2007 to 143 560 in 2016), including repeat testing in higher risk men and improvements in the uptake of ART after HIV diagnosis. However, increased screening probably provides only a partial explanation. 56 Dean Street, a sexual health service in London, diagnoses one in three new HIV infections in the capital and sees a quarter of newly diagnosed individuals in the UK. Since 2015, the clinic has seen an 80% reduction in diagnoses (figure). Similar trends have been seen in four other large London clinics. The decline in new infections seen at Dean Street occurred against a background of a significant increase in testing in high-risk gay men in 2014–15 which subsequently stabilised. Other important factors might have also played a part. Patients at the clinic commence HIV treatment within a median of 7 days of diagnosis. Whether this contributes substantially to a decrease in transmission deserves further study because knowledge of HIV status alone is associated with a reduction in risk behaviour for a variable period of time after diagnosis. Another important factor that needs to be considered as a major contributor to the decline in diagnoses is the use of HIV pre-exposure prophylaxis (PrEP). In the Autumn of 2014, the PROUD and IPERGAY PrEP studies were stopped early, after both showed an 86% reduction in HIV acquisition risk for people taking tenofovir disoproxil fumarate plus emtricitabine versus placebo. Gay men began to purchase generic PrEP from India as it is not available through the UK health system. This was facilitated by community activists who set up I Want PrEP Now offering advice and links to online pharmacies for people seeking to purchase PrEP on the internet. At the same time, 56 Dean Street launched a service offering support and monitoring for people buying generics online, including drug concentration testing to ensure authenticity. In addition, Dean Street PRIME, an intervention for people with at least a 10% chance For more on I Want PrEP Now see www.iwantprepnow.co.uk Published Online October 20, 2017 http://dx.doi.org/10.1016/ S2352-3018(17)30181-9

Histone Deacetylase Inhibitors Enhance CD4 T Cell Susceptibility to NK Cell Killing but Reduce NK Cell Function

In the search for a cure for HIV-1 infection, histone deacetylase inhibitors (HDACi) are being investigated as activators of latently infected CD4 T cells to promote their targeting by cytotoxic T-lymphocytes (CTL). However, HDACi may also inhibit CTL function, suggesting different immunotherapy approaches may need to be explored. Here, we study the impact of different HDACi on both Natural Killer (NK) and CTL targeting of HIV-1 infected cells. We found HDACi down-regulated HLA class I expression independently of HIV-1 Nef which, without significantly compromising CTL function, led to enhanced targeting by NK cells. HDACi-treated HIV-1-infected CD4 T cells were also more effectively cleared than untreated controls during NK co-culture. However, HDACi impaired NK function, reducing degranulation and killing capacity. Depending on the HDACi and dose, this impairment could counteract the benefit gained by treating infected target cells. These data suggest that following HDACi-induced HLA class I down-regulation NK cells kill HIV-1-infected cells, although HDACi-mediated NK cell inhibition may negate this effect. Our data emphasize the importance of studying the effects of potential interventions on both targets and effectors.

Not just PrEP: other reasons for London's HIV decline

www.thelancet.com/hiv Vol 4 April 2017 e153 Diagnoses started to fall in the autumn of 2015 (figure). In 2014, we opened Dean Street Express, reducing time to treatment for chlamydia and gonorrhoea from 10 days to 2 days. Given that both these infections are drivers of HIV transmission, their early treatment may have played a part in the decline in new infections. Additionally, the opening of Dean Street Express was linked to a significant increase in HIV testing in high risk men who have sex with men (MSM). Other factors likely to have had an effect are that we prescribe over a quarter of the HIV post-exposure prophylaxis in the UK (2637 of 9609 prescriptions in 2015), and the Dean Street Wellbeing Programme promoting regular testing in high risk MSM, including those practising chemsex. Not just PrEP: other reasons for London’s HIV decline