Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation.

OBJECTIVES: The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes. METHODS: We identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1 year. We analysed outcomes of viral suppression (< 200 HIV-1 RNA copies/mL) and appearance of new major drug resistance mutations (DRMs) using Cox and Poisson models, with stratification by new drug regimen (excluding 3TC/FTC) and Bayesian implementation, and estimated the effect of 3TC/FTC adjusted for individual and viral characteristics. RESULTS: We included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. We found a negative adjusted association between 3TC/FTC use and viral suppression [hazard ratio (HR) 0.84; 95% credibility interval (CrI) 0.71-0.98]. On subgroup analysis of individual drugs, there was no evidence of an association with viral suppression for 3TC (n = 184; HR 0.94; 95% CrI 0.73-1.15) or FTC (n = 454; HR 0.99; 95% CrI 0.80-1.19) amongst those on tenofovir-containing regimens, but we estimated a reduced rate of viral suppression for people on 3TC amongst those without tenofovir use (n = 481; HR 0.71; 95% CrI 0.54-0.90). We found no association between 3TC/FTC and detection of any new DRM (overall HR 0.92; 95% CrI 0.64-1.18), but found inconclusive evidence of a lower incidence rate of new DRMs (overall incidence rate ratio 0.69; 95% CrI 0.34-1.11). CONCLUSIONS: We did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir.

The people living with HIV stigma survey UK 2015: HIV-related sexual rejection and other experiences of stigma and discrimination among gay and heterosexual men.

We aim to understand the difference in stigma and discrimination, in particular sexual rejection, experienced between gay and heterosexual men living with HIV in the UK. The People Living with HIV StigmaSurvey UK 2015 recruited a convenience sample of persons with HIV through over 120 cross sector community organisations and 46 HIV clinics to complete an online survey. 1162 men completed the survey, 969 (83%) gay men and 193 (17%) heterosexual men, 92% were on antiretroviral therapy. Compared to heterosexual men, gay men were significantly more likely to report worrying about workplace treatment in relation to their HIV (21% vs. 11%), worrying about HIV-related sexual rejection (42% vs 21%), avoiding sex because of their HIV status (37% vs. 23%), and experiencing HIV-related sexual rejection (27% vs. 9%) in the past 12 months. In a multivariate logistic regression controlling for other sociodemographic factors, being gay was a predictor of reporting HIV-related sexual rejection in the past 12 months (aOR 2.17, CI 1.16, 4.02). Both gay and heterosexual men living with HIV experienced stigma and discrimination in the past 12 months, and this was higher for gay men in terms of HIV-related sexual rejection. Due to the high proportion of men reporting sexual rejection, greater awareness and education of the low risk of transmission of HIV among people on effective treatment is needed to reduce stigma and sexual prejudice towards people living with HIV.

Low levels of neurocognitive impairment detected in screening HIV-infected men who have sex with men: The MSM Neurocog Study.

This study aimed to determine the prevalence of HIV neurocognitive impairment in HIV-infected men who have sex with men aged 18-50 years, using a simple battery of screening tests in routine clinical appointments. Those with suspected abnormalities were referred on for further assessment. The cohort was also followed up over time to look at evolving changes. HIV-infected participants were recruited at three clinical sites in London during from routine clinical visits. They could be clinician or self-referred and did not need to be symptomatic. They completed questionnaires on anxiety, depression, and memory. They were then screened using the Brief Neurocognitive Screen (BNCS) and International HIV Dementia Scale (IHDS). Two hundred and five HIV-infected subjects were recruited. Of these, 59 patients were excluded as having a mood disorder and two patients were excluded due to insufficient data, leaving 144 patients for analysis. One hundred and twenty-four (86.1%) had a normal composite z score (within 1 SD of mean) calculated for their scores on the three component tests of the BNCS. Twenty (13.9%) had an abnormal z score, of which seven (35%) were symptomatic and 13 (65%) asymptomatic. Current employment and previous educational level were significantly associated with BNCS scores. Of those referred onwards for diagnostic testing, only one participant was found to have impairment likely related to HIV infection. We were able to easily screen for mood disorders and cognitive impairment in routine clinical practice. We identified a high level of depression and anxiety in our cohort. Using simple screening tests in clinic and an onward referral process for further testing, we were not able to identify neurocognitive impairment in this cohort at levels consistent with published data.

Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom.

OBJECTIVES: Transmission of drug-resistant HIV-1 has decreased in the UK since the early 2000s. This analysis reports recent trends and characteristics of transmitted drug resistance (TDR) in the UK from 2010 to 2013. METHODS: Resistance tests conducted in antiretroviral treatment (ART)-naïve individuals between 2010 and 2013 were analysed for the presence of transmitted drug resistance mutations (TDRMs), defined as any mutations from a modified 2009 World Health Organization surveillance list, or a modified 2013 International Antiviral Society-USA list for integrase tests. Logistic regression was used to examine associations between demographics and the prevalence of TDRMs. RESULTS: TDRMs were observed in 1223 (7.5%) of 16 425 individuals; prevalence declined from 8.1% in 2010 to 6.6% in 2013 (P = 0.02). The prevalence of TDRMs was higher among men who have sex with men (MSM) compared with heterosexual men and women (8.7% versus 6.4%, respectively) with a trend for decreasing TDRMs among MSM (P = 0.008) driven by a reduction in nucleoside reverse transcriptase inhibitor (NRTI)-related mutations. The most frequently detected TDRMs were K103N (2.2%), T215 revertants (1.6%), M41L (0.9%) and L90M (0.7%). Predicted phenotypic resistance to first-line ART was highest to the nonnucleoside reverse transcriptase inhibitors (NNRTIs) rilpivirine and efavirenz (6.2% and 3.4%, respectively) but minimal to NRTIs, including tenofovir, and protease inhibitors (PIs). No major integrase TDRMs were detected among 101 individuals tested while ART-naïve. CONCLUSIONS: We observed a decrease in TDRMs in recent years. However, this was confined to the MSM population and rates remained stable in those with heterosexually acquired HIV infection. Resistance to currently recommended first-line ART, including integrase inhibitors, remained reassuringly low.

A cross-sectional study to evaluate the association of hyperbilirubinaemia on markers of cardiovascular disease, neurocognitive function, bone mineral density and renal markers in HIV-1 infected subjects on protease inhibitors.

BACKGROUND: Ongoing inflammation in controlled HIV infection contributes to non-AIDS comorbidities. High bilirubin appears to exhibit an anti-inflammatory effect in vivo. We therefore examined whether increased bilirubin in persons with HIV was associated with differences in markers of inflammation and cardiovascular, bone, renal disease, and neurocognitive (NC) impairment. METHODS: This cross-sectional study examined inflammatory markers in individuals with stable HIV infection treated with two nucleoside reverse transcriptase inhibitors and a boosted protease inhibitor. Individuals recruited were those with a normal bilirubin (NBR; 0-17 µmol/L) or high bilirubin (>2.5 × upper limit of normal). Demographic and anthropological data were recorded. Blood and urine samples were taken for analyses. Pulse wave velocity (PWV) measurement, carotid intimal thickness (CIT), and calcaneal stiffness (CSI) were measured. Males were asked to answer a questionnaire about sexual function; NC testing was performed using CogState. RESULTS: 101 patients were screened, 78 enrolled (43 NBR and 35 HBR). Atazanavir use was significantly higher in HBR. Whilst a trend for lower CIT was seen in those with HBR, no significant differences were seen in PWV, bone markers, calculated cardiovascular risk (Framingham), or erectile dysfunction score. VCAM-1 levels were significantly lower in the HBR group. HBR was associated with lower LDL and triglyceride levels. NBR was associated with a calculated FRAX significantly lower than HBR although no associations were found after adjusting for tenofovir use. No difference in renal markers was observed. Component tests of NC testing revealed differences favouring HBR but overall composite scores were similar. DISCUSSION: High bilirubin in the context of boosted PI therapy was found not to be associated with differences in with the markers examined in this study. Some trends were noted and, on the basis of these, a larger, clinical end point study is warranted.

HIV-related neurocognitive impairment screening: the patient's perspective on its utility and psychological impact.

Despite ever improving advances in antiretroviral therapy, neurocognitive impairments such as asymptomatic and mild neurocognitive impairment remain a significant problem for the HIV-positive population. We distributed a post-neurocognitive impairment screening service evaluation questionnaire to assess satisfaction and anxiety. Subjects were HIV positive and aged 18-50. They were screened using the Brief Neurocognitive Score and International HIV Dementia Score as well as undergoing screening for anxiety (Generalised Anxiety Disorder Assessment [GAD-7]), depression (Participant Health Questionnaire Mood Scale [PHQ-9]) and memory (Everyday Memory Questionnaire [EMQ-R]). On completion, they were either reassured that the tests were normal or were referred for further investigation. Following assessment, subjects were asked to complete an anonymous satisfaction survey; 101 surveys were analysed. Forty-nine per cent of participants stated that they "felt better" following screening, 43% said it "made no difference", 6% stated it "worried me" and 1% "did not understand". On a scale of 0-10 of helpfulness, the mean score was 7.53. Forty-seven subjects indicated that they were referred for further investigation and 46 subjects that nothing else was needed; 8 reported they did not know. Those referred on rated satisfaction at a mean of 7.54/10 and those with normal screen as 7.09/10 (p = 0.46). Of the groups that were referred for further investigation, 6% said the test "worried them" compared to 4% in the non-referred group. Forty-nine per cent said they "felt better" despite an abnormal result compared to 50% in a normal screening result (p = 0.76). The results of this survey show that screening for neurocognitive impairment by this method is acceptable and helpful to participants. It did not lead to an increase in anxiety and there was no correlation between referred for further investigations and anxiety suggesting concerns about creating undue anxiety by screening and referral are unfounded.

Screening for HIV-related neurocognitive impairment in clinical practice: challenges and opportunities.

With increasingly successful management of HIV, focus has shifted away from AIDS-related complications to other chronic co-morbidities. For HIV-related cognitive problems, the true aetiopathogenesis and epidemiology remains unclear. Rather than a systematic review, this paper presents the challenges and the opportunities we faced in establishing our own clinical service. Papers were identified using Pubmed and the terms "screening", "HIV" and "neurocognitive". This article covers the background of HIV-associated neurocognitive disorders (HAND) with a focus on HIV-related neurocognitive impairment (NCI), detailing classification, prevalence, diagnostic categories and diagnostic uncertainties. Screening is discussed, including a comparison of the available screening tools for cognitive deficits in HIV-infected patients and the importance of practice effects. Discussed also are the normal ranges and the lack thereof and potential investigations for those found to have impairments. We conclude by discussing the role of NCI screening in routine clinical care at the current time.

A dedicated clinic for HIV-positive individuals over 50 years of age: a multidisciplinary experience.

The HIV-infected population is ageing. Issues including polypharmacy and co-morbidities led us to develop a dedicated clinic for HIV-infected individuals over 50. We describe our service evaluation after two years. The over 50 clinic commenced in January 2009. The team comprises a registrar, consultant, nurse practitioner and is supported by a pharmacist and mental health services. Patients undergo a full medication and drug interactions review, neurocognitive assessment, adherence self-assessment and investigations including therapeutic drug monitoring (TDM), coronary artery calcium scores (CACS) and bone mineral density. Over two years of activity, 150 patients attended the service. Median (range) age was 58 (50-88), all were on combined antiretroviral therapy and 38% (57/150) were on ≥3 non-HIV drugs. CACS was high (>90th centile) in 14%. Thirty-eight percent had osteopaenia and 18% had osteoporosis requiring treatment. Thirteen out of 125 men had an increased prostate specific antigen, four were diagnosed with prostate cancer. Drug interaction, TDM and neurocognitive assessments were useful for several patients. Asymptomatic patients over 50 in long-term follow-up had new pathologies detected through targeted screening. The clinic has improved general practitioner (GP) liaison and facilitated closer working relationships with other specialties. Patients have reacted positively to the clinic, particularly as many do not routinely access their GP.

Sexual dysfunction in HIV-positive men is multi-factorial: a study of prevalence and associated factors.

To establish the prevalence of sexual dysfunction amongst HIV-positive men and to determine the factors associated with dysfunction we conducted a cross-sectional study in seven European HIV treatment centres. Data on medical history, antiretroviral treatment and laboratory results were collected by interview and case record review. Sexual function was evaluated by the participant self-completion of a questionnaire based on the International Index of Erectile Function (IIEF) 711/929. Seventy-seven percent of participants returned the questionnaire. Data from 668 (72%) respondents were included. Thirty-three percent (95%CI: 29.4-36.5%) had moderate/severe erectile dysfunction (EDF) and 24% (95%CI: 20.9-27.3%) had moderate to severe impairment of sexual desire. Variables significantly associated with EDF in multivariable analysis were older age (greater than 40 years), heterosexual status, non-alcohol drinking status, depression, antidepressants, psychotropic medications and duration of ARV therapy. Low sexual desire (LSD) was associated with older age (greater than 40 years), depression and black African ethnicity. We establish that EDF and LSD are common in both ARV naïve and ARV experienced, HIV-positive individuals. Erectile dysfunction was associated with long duration of ARV treatment, with a significantly increased risk of dysfunction in the quartile with the longest period of exposure. No significant association was seen with specific classes of anti-retrovirals. Older age, and depression were the variables most consistently associated with both EDF and LSD.

Increasing detection of asymptomatic syphilis in HIV patients.

BACKGROUND/OBJECTIVES: The burden of new syphilis diagnoses in London has mainly been in men who have sex with men (MSM), many of whom are co-infected with HIV. Our HIV unit introduced regular serological screening for syphilis during routine follow up care to detect patients who may be at risk of asymptomatic infection. We assessed if this remained an effective and necessary strategy in the second year since introduction. METHODS: All HIV outpatients with newly positive syphilis serology between 1 May 2002 and 30 April 2003 were identified using a prospectively collected database. Only patients who were asymptomatic at the time of screening were included (cohort B). They were compared to patients in the exact preceding year (cohort A). RESULTS: 2655 patients had at least one CD4 count measured in the period (surrogate marker for patients having routine follow up bloods), of whom 2389 (90%) had syphilis serology performed. 40 individuals were found to have early asymptomatic infection (two were re-infections), compared to 26 patients in cohort A. These 40 patients represented 36% of all patients with infectious syphilis treated within our department and 56% of those who were HIV positive. The event rate in cohort B was 7.3 per 1000 patient years (CI 5.2 to 9.9) compared to 2.8 (CI 1.8 to 4.0) in cohort A. CONCLUSION: Routine screening is effective and has detected increasing numbers of HIV outpatients with early asymptomatic syphilis. Our department will continue this strategy for all HIV patients during their follow up care. We recommend that other units adopt similar initiatives that assist with regional control of the UK syphilis epidemic.

Prevalence and factors associated with sexual dysfunction among HIV-positive women in Europe.

Little is known on female sexual dysfunction (FSD) among HIV-positive women. A cross-sectional survey in seven European HIV centres was performed and data on medical history, antiretroviral treatment and laboratory results were collected. Sexual function was evaluated by the Female Sexual Function Index (FSFI). The data from 166 women were available (response rate=77%). The non-respondents had a lower CD4 cell count, were older and more frequently of sub-Saharan African origin. The overall median FSFI was 25.2 (interquartile range=19.3). Thirty-six women (25%) had a FSFI score < or = 10. Depression, irritability and anxiety were associated with a low FSFI score. The participants reported a significant decrease in sex functioning since HIV diagnosis but not since the start of antiretroviral treatment. Sexual dysfunction in women with HIV infection is frequent and is mainly driven by psychological factors and by the HIV diagnosis.

Is increased surveillance for asymptomatic syphilis in an HIV outpatient department worthwhile?

OBJECTIVES: Syphilis outbreaks have recently been reported in the United Kingdom, some of which have included cohorts of HIV positive individuals. As a result we commenced 3 monthly screening of syphilis serology (STS) for HIV positive patients having routine follow up blood tests. We assessed if there was an increased number of individuals being screened and also whether the screening programme was diagnosing early cases of syphilis. METHODS: Data from a 1 year period following introduction of screening (May 2001) were analysed and compared with data from the same period last year. The case notes of patients with a positive VDRL were reviewed to establish, firstly, whether these represented new diagnoses and, secondly, whether patients were asymptomatic at the time of screening. RESULTS: 2670 patients had at least one CD4 count measured in the period (surrogate for patients having routine bloods). Of these, 2266 patients had STS performed (85%). 38 patients had a positive VDRL. Of these, 20 were confirmed as having early syphilis which was asymptomatic at the time of screening. Six asymptomatic cases were also confirmed with newly positive TPPAs and a negative VDRL. These 26 asymptomatic cases represent 29% of all cases of early syphilis diagnosed in our department and 50% of cases in the HIV positive cohort. CONCLUSION: With intensive surveillance significant numbers of cases of asymptomatic early syphilis are being identified in a group of HIV individuals under routine follow up, at an earlier stage than would otherwise have been the case. This presents an opportunity to intervene not only to prevent clinical illness but also to institute infection control measures.

Sequencing to NRTI plus NNRTI-only combinations after virological failure of protease inhibitor-based combination HIV-1 therapy.

PURPOSE: To examine the success of sequencing to nucleoside reverse transcriptase inhibitor (NRTI) plus nonnucleoside reverse transcriptase inhibitor (NNRTI)-only combinations after virological failure of protease inhibitor (PI)-based combinations in NNRTI-naïve individuals. METHOD: This was an observational cohort study. RESULTS: 171 patients were identified. The group was highly antiretroviral therapy-experienced with median cumulative NRTI and PI durations prior to change of 53 months and 21 months, respectively. The median CD4 count and viral load (VL) prior to change were 228 cells/mm(3) and 24500 copies/mL. Overall, 37.4% had a VL below the limit of detection (50 copies/mL) at 12 months (intention-to-treat analysis). Markers associated with success at 12 months were efavirenz (EFV) use, the use of three NRTI+NNRTI combinations, and abacavir (ABC) use. In multivariate analysis, use of EFV remained highly significant (relative hazard of virological success of nevirapine [NVP] vs. EFV = 0.39; p =.003), while ABC use became nonsignificant. A benefit from the use of three NRTI + NNRTI regimens was observed. CONCLUSION: NRTI plus NNRTI-only combinations performed poorly, however the superior outcomes of patients treated with EFV are consistent with findings in cohort studies. The suggestion of benefit in patients receiving three NRTIs in addition to either NVP or EFV deserves further study in randomized trials.

Pneumonia due to antibiotic resistant Streptococcus pneumoniae and Pseudomonas aeruginosa in the HAART era.

Antibiotic resistance profiles are useful in directing therapeutic strategies during bacterial infections. Patterns of antimicrobial resistance in Streptococcus pneumoniae and Pseudomonas aeruginosa associated pneumonia were investigated in an HIV-1 infected cohort during the era of highly active antiretroviral therapy. The median CD4 count at presentation was significantly lower for cases of P aeruginosa than for S pneumoniae. However, the number of antibiotic resistant cases of P aeruginosa decreased throughout the study period, while the incidence of S pneumoniae remained unchanged. In contrast to pneumococcal pneumonia, we show that antiretrovirals have protected from pneumonia due to antibiotic resistant P aeruginosa. These findings have implications for the treatment of individuals presenting with serious infections in which antibiotic therapy needs to be instituted before identification and sensitivities are known.

What do patients attending HIV and GUM outpatient clinics want from service providers? Results from a large-scale consultation exercise in west London.

Our objectives were to understand patient demographic profiles, experiences of care and opinions about services. A questionnaire survey of 202 HIV patients and 389 genitourinary medicine (GUM) outpatients attending clinics during one week in 1999 was undertaken at a clinical directorate of HIV/GUM in west London. HIV and GUM patients differed by age (over 30: 84% vs 39%), sex (male: 88% vs 51%), and attendance (attended 6+ times: 55% vs 14%). Most indicated that they were satisfied with the general standard of care (97% HIV patients vs 95% GUM patients). Several clinic features were rated essential. When indicating reasons they might leave in the future, HIV patients were more likely to select leading edge care factors, such as lack of up-to-date treatment (54%). More GUM patients selected factors relating to convenience, such as waiting times (58%). In conclusion, most HIV and GUM patients were satisfied with their care, but differing experiences and opinions need to be addressed when planning services.