Pregnancy Management in HIV Viral Controllers: Twenty Years of Experience.

(1) Background: The evidence base for the management of spontaneous viral controllers in pregnancy is lacking. We describe the management outcomes of pregnancies in a series of UK women with spontaneous HIV viral control (<100 copies/mL 2 occasions before or after pregnancy off ART). (2) Methods: A multi-centre, retrospective case series (1999-2021) comparing pre- and post-2012 when guidelines departed from zidovudine-monotherapy (ZDVm) as a first-line option. Demographic, virologic, obstetric and neonatal information were anonymised, collated and analysed in SPSS. (3) Results: A total of 49 live births were recorded in 29 women, 35 pre-2012 and 14 post. HIV infection was more commonly diagnosed in first reported pregnancy pre-2012 (15/35) compared to post (2/14), p = 0.10. Pre-2012 pregnancies were predominantly managed with ZDVm (28/35) with pre-labour caesarean section (PLCS) (24/35). Post-2012 4/14 received ZDVm and 10/14 triple ART, p = 0.002. Post-2012 mode of delivery was varied (5 vaginal, 6 PLCS and 3 emergency CS). No intrapartum ZDV infusions were given post-2012 compared to 11/35 deliveries pre-2012. During pregnancy, HIV was detected (> 50 copies/mL) in 14/49 pregnancies (29%) (median 92, range 51-6084). Neonatal ZDV post-exposure prophylaxis was recorded for 45/49 infants. No transmissions were reported. (4) Conclusion: UK practice has been influenced by the change in guidelines, but this has had little impact on CS rates.

Prevalence of porA pseudogene deletion among Neisseria gonorrhoeae isolates referred to the UK's Gonococcal Resistance to Antimicrobials Surveillance Program.

porA pseudogene-negative Neisseria gonorrhoeae isolates produce false-negative results when examined by polymerase chain reaction (PCR) with porA pseudogene targets. In the present study, 533 representative gonococcal isolates received in 2011 via the Gonococcal Resistance to Antimicrobials Surveillance Program were examined to determine the prevalence of porA-negative isolates. Less than 0.4% (2/533) of isolates were found to be reproducibly negative with the porA real-time PCR but were confirmed as N. gonorrhoeae with molecular, biochemical and immunological confirmatory tests. Sequencing revealed both isolates contained the Neisseria meningitidis porA gene. Low prevalence indicates that although these isolates do not present a major public health problem, microbiologists should remain vigilant.

Effects on vitamin D, bone and the kidney of switching from fixed-dose tenofovir disoproxil fumarate/emtricitabine/efavirenz to darunavir/ritonavir monotherapy: a randomized, controlled trial (MIDAS).

BACKGROUND: Efavirenz (EFV) has been associated with reductions in vitamin D (25[OH]D) and tenofovir (TDF) with increased bone turnover, reductions in bone mineral density (BMD) and renal tubular dysfunction. We hypothesized that switching from fixed-dose TDF/emtricitabine (FTC)/EFV to darunavir/ritonavir monotherapy (DRV/r) might increase 25(OH)D and BMD, and improve renal tubular function. METHODS: Subjects with HIV RNA <50 copies/ml on TDF/FTC/EFV for ≥6 months were randomized 1:1 to ongoing TDF/FTC/EFV or DRV/r (800/100 mg once daily) for 48 weeks. The primary end point was change from baseline in 25(OH)D at week 48. Secondary end points included changes in BMD, bone turnover markers and renal tubular function. RESULTS: A total of 64 subjects (86% male, 66% white, mean [sd] CD4(+) T-cell count 537.3 [191.5]/mm(3)) were analysed. After adjustment for baseline 25(OH)D and demographics, at week 48 DRV/r monotherapy was associated with a +3.6 (95% CI 0.6, 6.6) ng/ml increase in 25(OH)D compared to TDF/FTC/EFV (P=0.02). DRV/r monotherapy was associated with an increase in BMD (+2.9% versus -0.003% at the neck of femur and +2.6% versus +0.008% at the lumbar spine for DRV/r versus TDF/FTC/EFV; P<0.05 for all) and reductions in bone biomarkers compared with those remaining on TDF/FTC/EFV. No significant difference in renal tubular function was observed. Reasons for discontinuation in the DRV/r arm included side effects (n=4) and viral load rebound (n=3), all of which resolved with DRV/r discontinuation or regimen intensification. CONCLUSIONS: Switching from TDF/FTC/EFV to DRV/r in patients with suppressed HIV RNA resulted in significant improvements in 25(OH)D and bone biomarkers, and a 2-3% increase in BMD.

¹8F-FDG PET/CT in HIV-related central nervous system pathology.

PURPOSE: To evaluate the utility of ¹8F-FDG PET/CT in suspected cerebral pathology in HIV-infected individuals. METHODS: ¹8F-FDG PET/CT scans from 29 HIV-infected individuals (29 brain scans, 22 whole-body scans) who presented with neurological symptoms and signs were retrospectively reviewed and compared with subsequent clinical investigations. RESULTS: The majority of patients (n=25) were referred to differentiate infection from malignant causes of cerebral pathology. Ten of the 11 patients with an eventual diagnosis of toxoplasmosis infection were correctly diagnosed by ¹8F-FDG PET/CT showing lesional uptake less than that of normal brain cortex (mean SUVmax 3.5, range 1.9 - 5.8). All five patients with a final diagnosis of primary central nervous system lymphoma (PCNSL) were correctly diagnosed by ¹8F-FDG PET/CT showing lesional uptake greater than that of normal brain cortex (mean SUVmax 18.8, range 12.4 - 29.9). Four of the five patients with ¹8F-FDG PET/CT features suggesting a vasculitic process had vasculitis confirmed as the final diagnosis. Three patients showed variable uptake in multiple cerebral lesions (including final diagnoses of tuberculosis and metastases from lung cancer in two patients) and there were four other miscellaneous diagnoses. In 12 patients biopsies were performed at sites guided by PET abnormality (7 brain, 5 lymph nodes) confirming or excluding significant disease in 11. CONCLUSION: ¹8F-FDG PET/CT is particularly useful for differentiating between infection and PCNSL in HIV-infected patients with a cerebral lesion on MRI or CT. ¹8F-FDG PET/CT was also a helpful tool in the diagnostic work-up of patients with other HIV-related cerebral pathology. Additional advantages of ¹8F-FDG PET/CT are the abilities to assess abnormally increased glucose metabolism in the body and to identify potential sites for biopsy.

A re-assessment of the epidemiology and patient characteristics of hepatitis D virus infection in inner city London.

OBJECTIVES: To re-assess the prevalence and patient characteristics of hepatitis D virus (HDV) infection among hepatitis B patients in inner city London. METHODS: All hepatitis B patients attending clinics over a 52 months period were tested for HDV antibody. All reactive samples were also tested for anti-HDV IgM and RNA. The characteristics of HDV seronegative patients first seen in the calendar year 2008 were compared with all HDV seropositive patients in the cohort. RESULTS: Of 1048 hepatitis B patients, 11 had equivocal anti-HDV serology (1%) and 22 were HDV seropositive (2.1%, 95%CI 1.39-3.16%); 12 were anti-HDV IgM positive and 15 HDV RNA positive. No patient with equivocal anti-HDV serology had detectable HDV RNA. Five HDV seropositive patients were intravenous drug users (22.7%); 17/22 were from abroad with 11/22 (50%) from sub-Saharan Africa. HDV seropositive patients had poorer laboratory parameters and were more likely to have evidence of cirrhosis. Triple infected (HIV/HBV/HDV) patients were also more likely to have cirrhosis than HIV/HBV dually infected patients. CONCLUSIONS: The prevalence of HDV in hepatitis B patients in inner city London was about 2%. The role of migration from endemic countries should be recognised.