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.

Oral Human Papillomavirus Infection in Men Who Have Sex with Men: A Systematic Review and Meta-Analysis.

BACKGROUND: The epidemiology of oral human papillomavirus (HPV) infection in men who have sex with men (MSM) differs from anogenital HPV infection. The impact of HPV vaccination has, to date, largely focussed on anogenital outcomes. Vaccination of MSM in the UK has been recommended and, if implemented, baseline estimates of oral HPV prevalence will be useful. METHODS: We searched Medline, Embase and psycINFO databases for studies reporting prevalence, incidence, and clearance of oral HPV infection in MSM. We performed a random-effects meta-analysis and meta-regression on prevalence estimates and summarised within-study risk factors for oral HPV DNA detection and incidence/clearance rates. We also performed a meta-analysis of the effect of MSM on oral HPV prevalence compared to heterosexual men. RESULTS: 26 publications were identified. The pooled prevalence of oral HPV16 from twelve estimates was 3.0% (95%CI 0.5-5.5) in HIV-negative and 4.7% (95%CI 2.1-7.3) in HIV-positive MSM. Median age of study participants explained 38% of heterogeneity (p<0.01) in HPV prevalence estimates (pooled = 17% and 29% in HIV-negative and HIV-positive, respectively; 22 estimates). Nine studies compared MSM to heterosexual men and found no difference in oral HPV prevalence (pooled OR 1.07 (95%CI 0.65-1.74)). The clearance rate was higher than incidence within studies. Type-specific concordance between oral and anogenital sites was rare. CONCLUSION: There was substantial heterogeneity between estimates of oral HPV prevalence in MSM populations that was partly explained by HIV status and median age.

Seven years of undiagnosed syphilis: a missed opportunity for mother and child.

We report the case of congenital syphilis diagnosed in a 7-year-old child after her 32-year-old mother was investigated for neurosyphilis. Our case illustrates the importance of antenatal syphilis screening and the need for a clear referral and management pathway for women with positive serology to ensure cases such as ours do not occur in the future.

Service impact of a change in HIV-1 viral load quantification assay.

INTRODUCTION: Due to discontinuation of the Siemens Versant HIV-1 RNA (bDNA) assay in the UK, our laboratory switched to the Roche Cobas Ampliprep/Taqman HIV-1 viral load (VL) assay (Roche) in April 2013. This assay has a lower cut-off of 20 RNA copies/mL (compared with <50 for the Siemens assay). Our laboratory demonstrated previously that a significant proportion (18%) of patients undetectable using bDNA HIV-1 RNA quantification exhibited low level viraemia (LLV) using the new assay. Local guidelines recommend that patients stable on therapy receive twice-yearly VLs. We evaluated the impact of the introduction of the new assay on our clinical service. METHODS: A retrospective cohort analysis of treated patients with stable undetectable VL by bDNA (<50 copies/mL) followed by ≥ one low-level (<400 copies/mL) VL with the Roche assay. Demographic data were collected in addition to frequency of VL testing and genotypic resistance assays. Referrals to virtual clinic (VC) were recorded. Patients were identified using laboratory data and information collected from electronic patient records. RESULTS were analyzed with SPSS v18. RESULTS: One hundred and ninety patients were included. DEMOGRAPHICS: 79.5% male; 60.6% homosexual; mean age of 46 years. Duration on stable treatment was 46.35 (std. dev. 38.15) months. Current treatment regimens were 43.3% PI-based; 43.3% NNRTI-based and 13.7% other. Patients were stratified into VL 20-49 copies/mL (n=109); VL 50-199 copies/mL (n=71) and VL 200-399 copies/mL (n=10). In total, there were 471 VLs measured of which 274 were additional as a result of the assay switch. This resulted in six HIV-1 genotype requests and 16 VC discussions (Table 1). Longer duration on HAART was associated with reduced frequency of VL testing. The relative risk of ongoing detectability according to drug class are: PI 1.62 (95% CI 1.18-2.21); NNRTI 0.507 (95% CI 0.30-0.85) and other 1.09 (95% CI 0.48-2.43). CONCLUSIONS: Changes in assay can result in difficulties in interpretation of patient results. The assay switch in our service had significant impact on patient and staff time and cost with an increase in patient recalls; increased frequency of VL measurement, genotypes and discussions in VC. Choice of assay is paramount to running an efficient and cost-effective clinical service.

Enhanced normalisation of CD4/CD8 ratio with early antiretroviral therapy in primary HIV infection.

INTRODUCTION: Despite normalization of total CD4 counts, ongoing immune dysfunction is noted amongst those on antiretroviral therapy (ART). Low CD4/CD8 ratio is associated with a high risk of AIDS and non-AIDS events and may act as a marker of immune senescence [1]. This ratio is improved by ART although normalization is uncommon (~7%) [2]. The probability of normalization of CD4 count is improved with immediate ART initiation in primary HIV infection (PHI) [3]. We examined whether CD4/CD8 ratio similarly normalized in immediate vs. deferred ART at PHI. MATERIAL AND METHODS: Using data from the SPARTAC trial and the UK Register of HIV Seroconverters, we examined the effect of ART with time (continuous) from HIV seroconversion (SC) on CD4/CD8 ratio (≥1) adjusted for sex, risk group, ethnicity, enrolment from an African site and both CD4 count and age at ART initiation. We also examined that effect by dichotomizing HIV duration at ART initiation (ART started within six months of SC: early ART; ART initiated>six months after SC: deferred). We also considered time to CD4 count normalization (≥900 cells/mm(3)). RESULTS: In total, 353 initiated ART with median (IQR) 97.9 (60.5, 384.5) days from estimated seroconversion; 253/353 early ART, 100 deferred ART. At one year after starting ART, 114/253 (45%) early ART had normalized CD4/8 ratio, compared with 11/99 (11%) in the deferred group, whilst 83/253 (33%) of early ART had normalized CD4 counts, compared with 3/99 (3%) in the deferred group. Individuals initiating within six months of PHI were significantly more likely to reach normal ratio than those initiating later (HR, 95% CI 2.96, 1.75 - 5.01, p<0.001). The longer after SC ART was initiated, the reduced likelihood of achieving normalization of CD4/CD8 ratio (HR 0.98, 95% CI 0.96 - 0.99 for each 30-day increase). CD4 count at ART initiation was also associated with normalization, as expected (HR 1.002, 95% CI 1.001 - 1.002, p<0.001). There was an association between normal CD4/CD8 ratio and being virally suppressed (<400 copies HIV RNA/ml) p<0.001. CD4 count normalization was also significantly more likely for those initiating early (HR 5.00, 95% CI 1.52 - 16.41, p=0.008). CONCLUSIONS: The likelihood of achieving normalization of CD4/CD8 ratios was increased if ART was initiated within six months of PHI. Higher CD4/CD8 ratio may reflect a more "normal" immune phenotype conferring enhanced prognosis and predict post-treatment control.

Cholecystectomy or Cholelithiasis - a Missed Marker for Hyperlipidaemia? A Combined Retrospective and Prospective Study.

BACKGROUND: Multiple studies have shown an association between gallstones and abnormal lipids and the latter increases the risk of coronary artery disease and stroke. Our study investigates the current incidence of lipid abnormalities in patients who have undergone cholecystectomy (retrospective study) and who have gallstones (prospective study). METHODS: We conducted a retrospective analysis of the lipid profiles of 715 patients who underwent cholecystectomy in a rural district general hospital from 2003 to 2006. Details of the cholecystectomy patients were obtained from Patient Information and Management System (PIMS) and cross-referenced with biochemical and histological databases. Following this a prospective study was undertaken of 129 patients presenting with gallstones. RESULTS: Of the 715 patients, three quarters were women. Only 36.2% of women and 36.9% of men who had a cholecystectomy had a full lipid profile including high density lipoproteins (HDL) and low density lipoproteins (LDL). Of these, 76.4% of women and 70.7% of men had an abnormal lipid profile. In the prospective group, 91.1 % of women and 96.3 % of men had a full lipid profile. These were abnormal in 81.4% of women and 70.4 % of men. Hypercholesterolemia and raised LDL were the most common abnormalities in both sexes. Hypertriglyceridaemia was common in both sexes in both the groups. CONCLUSIONS: Patients who have had a cholecystectomy or gallstones should have a full fasting lipid profile, including HDL and LDL, as a large proportion will be abnormal. Current guidelines suggest they are at an increased risk of cardiovascular disease and should be treated.