Jennifer Tosswill

Prospective study of HTLV-I infection in an initially asymptomatic cohort

A prospective clinical study of 20 initially asymptomatic HTLV-I-seropositive carriers was commenced in 1991 to determine the natural history of the infection in relation to HTLV-I proviral load, immune responses, and lymphocyte phenotype. Proviral load varied widely between carriers but was relatively constant within an individual over time. The lymphocyte phenotype and prevalence of activated lymphocytes were not predictive of disease and the magnitude of the cytotoxic T-lymphocyte response to HTLV-I was independent of proviral load. Incident conditions, some related to HTLV-I infection, including a case of HTLV-I-associated myelopathy (HAM), were documented in 9 carriers. Development of myelopathy and uveitis was associated with high peripheral blood HTLV-I proviral load that predated symptoms. Persistently high proviral load appears to predate the development of HTLV-I-associated inflammation in neuro-ophthalmic tissue.

British HIV Association guidelines for the management of HIV infection in pregnant women 2012 (2014 interim review)

Emtricitabine/tenofovir/rilpivirine as a single‐tablet regimen (STR) is widely used without licence in treatment‐experienced patients. The purpose of this retrospective observational study was to assess viral suppression of ART‐experienced patients switching to STR.

Recent infection testing algorithm (RITA) applied to new HIV diagnoses in England, Wales and Northern Ireland, 2009 to 2011

In 2009, Public Health England (PHE) introduced the routine application of a recent infection testing algorithm (RITA) to new HIV diagnoses, where a positive RITA result indicates likely acquisition of infection in the previous six months. Laboratories submit serum specimens to PHE for testing using the HIV 1/2gO AxSYM assay modified for the determination of HIV antibody avidity. Results are classified according to avidity index and data on CD₄ count, antiretroviral treatment and the presence of an AIDS-defining illness. Between 2009 and 2011, 38.4% (6,966/18,134) of new HIV diagnoses in England, Wales and Northern Ireland were tested. Demographic characteristics of those tested were similar to all persons with diagnosed HIV. Overall, recent infection was 14.7% (1,022/6,966) and higher among men who have sex with men (MSM) (22.3%, 720/3,223) compared with heterosexual men and women (7.8%, 247/3,164). Higher proportions were among persons aged 15-24 years compared with those ≥50 years (MSM 31.2% (139/445) vs 13.6% (42/308); heterosexual men and women 17.3% (43/249) vs 6.2% (31/501)). Among heterosexual men and women, black Africans were least likely to have recent infection compared with whites (4.8%, 90/1,892 vs 13.3%, 97/728; adjusted odds ratio: 0.6; 95% CI: 0.4-0.9). Our results indicate evidence of ongoing HIV transmission during the study period, particularly among MSM.

Evaluation of an Enzyme Immunoassay for the Combined Detection of Antibodies to HIV-1, HIV-2, HTLV-I and HTLV-II

ObjectiveTo assess the sensitivity and specificity of a newly-developed assay (Bioelisa HIV-1 + 2, HTLV-1 + 2) for the simultaneous detection of HIV-1, HIV-2, HTLV-I and HTLV-II antibodies in human serum or plasma specimens. MethodsA panel of 775 well characterized serum or plasma samples was studied. This included samples confirmed to contain antibodies to HIV-1 (n = 46), HIV-2 (n = 14), HTLV-I (n = 49) and HTLV-II (n = 12), samples containing low litres of anti-HIV antibody (n = 14) and samples collected during HIV seroconversion (n = 36). Eighty-three sera samples which were reactive in one or more HIV or HTLV screening assays, but which could not be confirmed to contain anti-HIV-1/2 or anti-HTLV-I/ll antibodies, were also examined. ResultsExcluding the seroconversion samples and those selected on the basis of false reactivity in other screening assays, the Bioelisa kit had a sensitivity of 100% for antibody to all four viruses and a specificity of 98.8%. The ability of the kit to detect anti-HIV during seroconversion was similar to that of several other synthetic HIV-antigen-based screening kits currently in use. ConclusionsOur findings indicate that the Bioelisa kit is sufficiently accurate to screen for both HIV and HTLV infections and that it warrants larger scale trials. Its use might allow blood donor screening for HTLV infection to be introduced more widely at modest extra cost.

O4 Hiv incidence among people who attend sexual health clinics in england in 2012: estimates using a biomarker for recent infection

Introduction In England, 80% of HIV diagnoses are in sexually transmitted infection (STI) clinics. Since 2009, Public Health England offered testing for recent HIV infection. Aim To estimate HIV incidence among STI clinic attendees in 2012. Methods The AxSYM avidity assay, modified to determine antibody avidity, was conducted on aliquots of newly diagnosed persons and results linked to the national HIV database. An incident case was defined as avidity <0.8, no antiretroviral treatment or AIDS and viral load ≥400 copies/mL at diagnosis. The number of persons tested for HIV was assessed using the Genitourinary Medicine Clinic Activity Dataset. We estimated and adjusted for a 1.9% (95% C.I. 1.0%–3.4%) false recent rate and used 202 days as the mean duration of recent infection to calculate incidence rates. Results Of 212 STI clinics in England, 150(71%) submitted specimens for recent infection testing, comprising 3,930 persons newly diagnosed; 50% were MSM. The number of HIV tests/diagnosis was 210 for all clinic attendees, 38 for MSM, 403 for all heterosexuals and 46 for black African heterosexuals. HIV incidence was 0.15% (95% C.I. 0.13–0.18%) for all attendees, 1.22% (95% C.I. 1.07–1.42%) for MSM, 1.41% (95% C.I. 1.21%-1.66%) for MSM in London, 0.03% (95% C.I. 0.02–0.04%) for heterosexuals and 0.13% (0.05–0.22%) for black African heterosexuals. Discussion/conclusion Testing for recent HIV infection combined with routinely collected clinical data provides robust and timely national estimates of HIV incidence. HIV incidence among MSM and black African heterosexuals attending STI clinics was 40 and nine times higher respectively than among all heterosexuals, and exceeds the WHO-defined elimination threshold of 0.1%.

Enhanced surveillance of HIV-1 drug resistance in recently infected MSM in the UK

Objectives To determine the prevalence of inferred low-frequency HIV-1 transmitted drug resistance (TDR) in MSM in the UK and its predicted effect on first-line therapy. Methods The HIV-1 pol gene was amplified from 442 newly diagnosed MSM identified as likely recently infected by serological avidity testing in 2011–13. The PCR products were sequenced by next-generation sequencing with a mutation frequency threshold of >2% and TDR mutations defined according to the 2009 WHO surveillance drug resistance mutations list. Results The majority (75.6%) were infected with subtype B and 6.6% with rare complex or unique recombinant forms. At a mutation frequency threshold of >20%, 7.2% (95% CI 5.0%–10.1%) of the sequences had TDR and this doubled to 15.8% (95% CI 12.6%–19.6%) at >2% mutation frequency (P < 0.0001). The majority (26/42, 62%) of low-frequency variants were against PIs. The most common mutations detected at >20% and 2%–20% mutation frequency differed for each drug class, these respectively being: L90M (n = 7) and M46IL (n = 10) for PIs; T215rev (n = 9) and D67GN (n = 4) for NRTIs; and K103N (n = 5) and G190E (n = 2) for NNRTIs. Combined TDR was more frequent in subtype B than non-B (OR = 0.38; 95% CI = 0.17–0.88; P = 0.024) and had minimal predicted effect on recommended first-line therapies. Conclusions The data suggest differences in the types of low-frequency compared with majority TDR variants that require a better understanding of the origins and clinical significance of low-frequency variants. This will better inform diagnostic and treatment strategies.

Epidemiology of Human T-cell lymphotropic viruses (HTLV) in England and Wales, 2003-2012

We report on the epidemiology of HTLV in England and Wales (EW 721/818). Two-thirds were women (64%; 573/889) and 87% were aged ≥35 years (768/887). Where ethnicity was reported (568), black Caribbeans accounted for 59% (337) of diagnoses, followed by whites (21%; 117), black Africans (11%; 66) and persons of Indian-subcontinent ethnicity (3%; 18). 43% (142/338) of people diagnosed probably acquired HTLV infection in the UK and 40% (135/338) in Latin America/ Caribbean. The majority of diagnoses were made among those exposed through mother-to-child transmission and/or heterosexual contact (90%; 381/423). For persons presenting with HTLV-related symptoms (559), the median age was 57 years and 45 years for those without symptoms (331). Median age for persons reported with adult T cell lymphoma (117) was 59 years and 55 years for HTLV-I-associated myelopathy (74). Of 283 symptomatic infections, 87% (247) were among black African/Caribbeans. 75 (8.4%) persons died over the decade, 84% (63) within one year of HTLV diagnosis. Though rare in E&W, HTLV infection is life-long and can result in debilitating disease. Enhanced surveillance remains of public health importance to continue building an epidemiological picture of HTLV and to better understand clinical disease progression.

HIV incidence among sexual health clinic attendees in England: First estimates for black African heterosexuals using a biomarker, 2009-2013

Introduction The HIV epidemic in England is largely concentrated among heterosexuals who are predominately black African and men who have sex with men (MSM). We present for the first time trends in annual HIV incidence for adults attending sexual health clinics, where 80% of all HIV diagnoses are made. Methods We identified newly diagnosed incident HIV using a recent infection testing algorithm (RITA) consisting of a biomarker (AxSYM assay, modified to determine antibody avidity), epidemiological and clinical information. We estimated HIV incidence using the WHO RITA formula for cross-sectional studies, with HIV testing data from sexual health clinics as the denominator. Results From 2009 to 2013, each year, between 9,700 and 26,000 black African heterosexuals (of between 161,000 and 231,000 heterosexuals overall) were included in analyses. For the same period, annually between 19,000 and 55,000 MSM were included. Estimates of HIV incidence among black Africans increased slightly (although non-significantly) from 0.15% (95% C.I.0.05%-0.26%) in 2009 to 0.19% (95% C.I.0.04%-0.34%) in 2013 and was 4-5-fold higher than among all heterosexuals among which it remained stable between 0.03% (95% C.I.0.02%-0.05%) and 0.05% (95% C.I.0.03%-0.07%) over the period. Among MSM incidence was highest and increased (non-significantly) from 1.24% (95%C.I 0.96–1.52%) to 1.46% (95% C.I 1.23%-1.70%) after a peak of 1.52% (95%C.I 1.30%-1.75%) in 2012. Conclusion These are the first nationwide estimates for trends in HIV incidence among black African and heterosexual populations in England which show black Africans, alongside MSM, remain disproportionately at risk of infection. Although people attending sexual health clinics may not be representative of the general population, nearly half of black Africans and MSM had attended in the previous 5 years. Timely and accurate incidence estimates will be critical in monitoring the impact of the reconfiguration of sexual health services in England, and any prevention programmes such as pre-exposure prophylaxis.

Human T-lymphotropic viruses (HTLV) in England and Wales, 2004 to 2013: testing and diagnoses

Human T-lymphotropic virus (HTLV) infection has been under enhanced surveillance in England and Wales since 2002, however, little is known about testing patterns. Using data from two surveillance systems held at Public Health England, we described HTLV antibody testing patterns between 2008 and 2013 and the demographic and clinical characteristics of persons diagnosed with HTLV in England and Wales between 2004 and 2013. An increase in HTLV testing was observed in England between 2008 and 2013 (3,581 to 7,130). Most tests (82%; 7,597/9,302) occurred within secondary care, 0.5% (48/9,302) of persons were reactive for HTLV antibodies and 0.3% (27/9,302) were confirmed positive. Increasing age and female sex were predictors of a reactive HTLV screen and confirmed diagnosis. Testing in primary care including sexual health and antenatal services was infrequent. Between 2004 and 2013, 858 people were diagnosed with HTLV, most of whom were female (65%; 549/851), of black Caribbean ethnicity (60%), not born in the United Kingdom (72%; 369/514) and asymptomatic at diagnosis (45%; 267/595). Despite increased testing, the epidemiology and clinical features of those diagnosed with HTLV have remained consistent. Apart from donor screening, testing for HTLV infection remains uncommon, except to diagnose associated disease.

Time to first positive HIV-1 DNA PCR may differ with antiretroviral regimen in infants infected with non-B subtype HIV-1

Objective: To evaluate the association of type and timing of prophylactic maternal and infant antiretroviral regimen with time to first positive HIV-1 DNA PCR test, in nonbreastfed HIV-infected infants, from populations infected predominantly with HIV-1 non-B subtype virus. Design: Analysis of combined data on nonbreastfed HIV-infected infants from prospective cohorts in Botswana, Thailand, and the United Kingdom (N = 405). Methods: Parametric models appropriate for interval-censored outcomes estimated the time to first positive PCR according to maternal or infant antiretroviral regimen category and timing of maternal antiretroviral initiation, with adjustment for covariates. Results: Maternal antiretroviral regimens included: no antiretrovirals (n = 138), single-nucleoside analog reverse transcriptase inhibitor (n = 165), single-dose nevirapine with zidovudine (n = 66), and combination prophylaxis with 3 or more antiretrovirals [combination antiretroviral therapy (cART), n = 36]. Type of maternal/infant antiretroviral regimen and timing of maternal antiretroviral initiation were each significantly associated with time to first positive PCR (multivariate P < 0.0001). The probability of a positive test with no antiretrovirals compared with the other regimen/timing groups was significantly lower at 1 day after birth, but did not differ significantly after age 14 days. In a subgroup of 143 infants testing negative at birth, infant cART was significantly associated with longer time to first positive test (multivariate P = 0.04). Conclusion: Time to first positive HIV-1 DNA PCR in HIV-1-infected nonbreastfed infants (non-B HIV subtype) may differ according to maternal/infant antiretroviral regimen and may be longer with infant cART, which may have implications for scheduling infant HIV PCR-diagnostic testing and confirming final infant HIV status.