Distinct Inflammatory Phenotypes are associated with subclinical and clinical Cardiovascular disease in People living with HIV.

Despite inflammation being implicated in cardiovascular disease (CVD) in people with HIV (PWH), considerable heterogeneity within populations of PWH exists. Stratifying CVD risk based on inflammatory phenotype could play an important role. Using principal component analyses and unsupervised hierarchical clustering, we examined 38 biomarkers to identify inflammatory phenotypes in two independent cohorts of PWH. We identified three distinct inflammatory clusters present in both cohorts that associated with altered risk of both subclinical CVD (cohort 1) and prevalent clinical CVD (cohort 2) after adjusting for CVD risk factors. These data support precision medicine approaches to enhance CVD risk assessment in PWH.

A rapid review of antenatal hepatitis C virus testing in the United Kingdom.

BACKGROUND: The United Kingdom (UK) has committed to the World Health Organization's viral hepatitis elimination targets. New case finding strategies, such as antenatal testing, may be needed to achieve these targets. We conducted a rapid review to understand hepatitis C-specific antibody (anti-HCV) and HCV RNA test positivity in antenatal settings in the United Kingdom to inform guidance. METHODS: Articles and conference abstracts published between January 2000 and June 2022 reporting anti-HCV testing in antenatal settings were identified through PubMed and Web of Science searches. Results were synthesised using a narrative approach. RESULTS: The search identified 2,011 publications; 10 studies were included in the final synthesis. Seven studies used anonymous testing methods and three studies used universal opt-out testing. Anti-HCV test positivity ranged from 0.1 to 0.99%, with a median value of 0.38%. Five studies reported HCV RNA positivity, which ranged from 0.1 to 0.57% of the testing population, with a median value of 0.22%. One study reported cost effectiveness of HCV and found it to be cost effective at £9,139 per quality adjusted life years. CONCLUSION: The relative contribution of universal opt-out antenatal testing for HCV should be reconsidered, as antenatal testing could play an important role in new case-finding and aid achieving elimination targets.

Evaluating virological outcomes in people with HIV on stable antiretroviral therapy with reduced frequency of HIV viral load monitoring during the COVID-19 pandemic.

OBJECTIVES: In response to the COVID-19 pandemic, HIV outpatient attendances were restricted from March 2020, resulting in reduced frequency of HIV viral load (VL) monitoring (previously 6-monthly) in clinically stable and virologically suppressed people living with HIV (PLWH). We investigated virological outcomes during this period of reduced monitoring and compared with the previous year, prior to the COVID-19 pandemic. METHODS: People living with HIV with undetectable VL (<200 HIV RNA copies /mL) on antiretroviral therapy (ART) were identified from March 2018 to February 2019. We determined VL outcomes during the pre-COVD-19 period (March 2019-February 2020) and the COVID-19 period (March 2020-February 2021) when monitoring was restricted. Frequency and longest durations between VL tests in each period were evaluated, and virological sequelae in those with detectable VL were determined. RESULTS: Of 2677 PLWH virologically suppressed on ART (March 2018-February 2019), VLs were measured and undetectable in 2571 (96.0%) and 2003 (77.9%) in the pre-COVID and COVID periods, respectively. Mean (SD) numbers of VL tests were 2.3 (1.08) and 1.1 (0.83) and mean longest duration between VL tests was 29.5 weeks (SD 8.25, 3.1% were ≥12 months) and 43.7 weeks (12.64, 28.4% were ≥12 months), in the pre-COVID and COVID periods, respectively. Of 45 individuals with one or more detectable VL during the COVID-19 period, two developed new drug resistance mutations. CONCLUSION: Reduced VL monitoring was not associated with poorer virological outcomes in the majority of stable individuals receiving ART. One in 20 individuals had not returned for VL testing after ≥31 months and the risk of harm in these individuals is unknown.

The Global Task Force for Chronic Pain in People with HIV (PWH): Developing a research agenda in an emerging field.

Chronic pain is a common comorbidity in people with HIV (PWH), with prevalence estimates of 25-85%. Research in this area is growing, but significant gaps remain. A Global Task Force of HIV experts was organized to brainstorm a scientific agenda and identify measurement domains critical to advancing research in this field. Experts were identified through literature searches and snowball sampling. Two online questionnaires were developed by Task Force members. Questionnaire 1 asked participants to identify knowledge gaps in the field of HIV and chronic pain and identify measurement domains in studies of chronic pain in PWH. Responses were ranked in order of importance in Questionnaire 2, which was followed by a group discussion. 29 experts completed Questionnaire 1, 25 completed Questionnaire 2, and 21 participated in the group. Many important clinical and research priorities emerged, including the need to examine etiologies of chronic pain in PWH. Pain-related measurement domains were discussed, with a primary focus on domains that could be assessed in a standardized manner across various cohorts that include PWH in different countries. We collaboratively identified clinical and research priorities, as well as gaps in standardization of measurement domains, that can be used to move the field forward.

How do we measure unmet need within sexual and reproductive health? A systematic review.

BACKGROUND: Addressing health inequality with sexual and reproductive health requires an understanding of unmet need within a range of populations. This review examined the methods and definitions that have been used to measure unmet need, and the populations most frequently assessed. METHODS: Five databases (PubMed, Web of Science, Scopus, The Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Health Management and Policy Database (HMIC)) were searched for studies that described quantitative measurement of unmet need within sexual and/or reproductive health between 2010 and 2021. A narrative synthesis was then undertaken to ascertain themes within the literature. RESULTS: The database search yielded 19,747 papers; 216 papers were included after screening. 190 studies assessed unmet reproductive health need, of which 137 were analyses of trends among people living in low/lower-middle income countries; 181 used cross-sectional data, with only nine analyses being longitudinal. Eighteen studies analysed unmet sexual health need, of which 12 focused on high and upper-middle income populations. 16 papers used cross-sectional analyses. The remaining 10 studies examined unmet need for a combination of sexual and reproductive health services, eight among populations from upper-middle or high income countries. All were cross-sectional analyses. 165 studies used the Demographic and Health Surveys (DHS) definition of unmet need; no other standardised definition was used among the remaining papers. DISCUSSION: There is a significant focus on unmet need for contraception among women in low income countries within the published literature, leaving considerable evidence gaps in relation to unmet need within sexual health generally and among men in particular, and unmet reproductive health need in high income settings. In addition, using an increased range of data collection methods, analyses and definitions of unmet need would enable better understanding of health inequality in this area.

Mortality and AIDS-defining events among young people following transition from paediatric to adult HIV care in the UK.

OBJECTIVES: To investigate risk of AIDS and mortality after transition from paediatric to adult care in a UK cohort of young people with perinatally acquired HIV. METHODS: Records of people aged ≥ 13 years on 31 December 2015 in the UK paediatric HIV cohort (Collaborative HIV Paediatric Study) were linked to those of adults in the UK Collaborative HIV Cohort (CHIC) cohort. We calculated time from transition to a new AIDS event/death, with follow-up censored at the last visit or 31 December 2015, whichever was the earliest. Cumulative incidence of and risk factors for AIDS/mortality were assessed using Kaplan-Meier and Cox regression. RESULTS: At the final paediatric visit, the 474 participants [51% female, 80% black, 60% born outside the UK, median (interquartile range) age at antiretroviral therapy (ART) initiation = 9 (5-13) years] had a median age of 18 (17-19) years and CD4 count of 471 (280-663) cell/µL; 89% were prescribed ART and 60% overall had a viral load ≤ 400 copies/mL. Over median follow-up in adult care of 3 (2-6) years, 35 (8%) experienced a new AIDS event (n = 25) or death (n = 14) (incidence = 1.8/100 person-years). In multivariable analyses, lower CD4 count at the last paediatric visit [adjusted hazard ratio = 0.8 (95% confidence interval: 0.7-1.0)/100 cells/µL increment] and AIDS diagnosis in paediatric care [2.7 (1.4-5.5)] were associated with a new AIDS event/mortality in adult care. CONCLUSIONS: Young people with perinatally acquired HIV transitioning to adult care with markers of disease progression in paediatric care experienced poorer outcomes in adult care. Increased investment in multidisciplinary specialized services is required to support this population at high risk of morbidity and mortality.

Respiratory symptoms and chronic bronchitis in people with and without HIV infection.

OBJECTIVES: High rates of respiratory symptoms and chronic bronchitis (CB) are reported in people with HIV infection (PWH). We investigated the prevalence of respiratory symptoms and CB in PWH and HIV-negative people in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study. METHODS: Assessment of respiratory symptoms and CB was undertaken using the modified form of the St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease (COPD). Univariate (χ2 tests, Mann-Whitney U tests and Spearman's rank correlation) and multivariable (linear and logistic regression) analyses were performed to consider associations of respiratory symptoms with demographic, lifestyle and HIV-related parameters, and with depressive symptoms and quality of life. RESULTS: Among the 619 participants, respiratory Symptom scores were higher in older and younger PWH compared to older HIV-negative people, with median (interquartile range) scores of 17.7 (6.2, 39.5), 17.5 (0.9, 30.0) and 9.0 (0.9, 17.5), respectively (P = 0.0001); these differences remained significant after confounder adjustment. Sixty-three participants (10.2%) met the criteria for CB [44 (14.0%) older PWH, 14 (9.2%) younger PWH, and five (3.3%) older HIV-negative people; P = 0.002], with these differences also remaining after adjustment for confounding variables, particularly smoking status [older vs. younger PWH: odds ratio (OR) 4.48 (95% confidence interval (CI) 1.64, 12.30); P = 0.004; older PWH vs. HIV-negative people: OR 4.53 (95% CI 1.12, 18.28); P = 0.03]. Respiratory symptoms and CB were both associated with greater depressive symptom scores and poorer quality of life. No strong associations were reported between CB and immune function, HIV RNA or previous diagnosis of any AIDS event. CONCLUSIONS: Respiratory symptoms and CB are more common in PWH than in demographically and lifestyle-similar HIV-negative people and are associated with poorer mental health and quality of life.

Antiretroviral treatment outcomes among late HIV presenters initiating treatment with integrase inhibitors or protease inhibitors.

OBJECTIVES: The aim of the study was to investigate the efficacy and safety of first-line antiretroviral therapy (ART) with integrase inhibitor (INI) or protease inhibitor (PI)-based regimens in patients with low CD4 cell counts and/or an AIDS-defining disease. METHODS: We conducted a retrospective, multicentre analysis to investigate discontinuation proportions and virological response in patients with CD4 cell counts < 200 cells/µL and/or AIDS-defining disease when starting first-line ART. Proportions of those discontinuing ART were compared using univariate analysis. Virological response was analysed using the Food & Drug Administration (FDA) snapshot analysis (HIV-1 RNA < 50 HIV-1 RNA copies/mL at week 48). RESULTS: Two hundred and eighteen late presenters were included in the study: 13.8% were women and 23.8% were of non-European ethnicity, and the mean baseline CD4 count was 91 cells/µL (standard deviation 112 cells/µL). A total of 131 late presenters started on INI- and 87 on PI-based treatment. It was found that 86.1% of patients treated with INIs and 81.1% of patients treated with PIs had a viral load < 50 copies/mL at week 48; proportions of discontinuation because of adverse events were 6.1% in the INI group and 11.5% in the PI group. No significant differences in discontinuation proportions were observed at week 12 or 48 between INI- and PI-based regimens (P = 0.76 and 0.52, respectively). Virological response was equally good in those receiving INIs and those receiving PIs (86.1% vs. 81.1%, respectively; P = 0.36). CONCLUSIONS: In a European cohort of late presenters starting first-line INI or PI-based ART regimens, there were no significant differences in discontinuation proportions or virological response at week 48.

Monitoring of older HIV-1-positive adults by HIV clinics in the United Kingdom: a national quality improvement initiative.

OBJECTIVES: The aim of the study was to describe a UK-wide process to assess adherence to guidelines for the routine investigation and monitoring of HIV-positive adults aged ≥ 50 years and provide clinical services with individual feedback to support improvement in quality of care. METHODS: The British HIV Association (BHIVA) invited HIV clinical care sites to provide retrospective data from case notes of up to 40 adults aged ≥ 50 years with HIV-1 infection attending the clinic for care during 2017 and/or 2018, using a structured dynamic online questionnaire. RESULTS: A total of 4959 questionnaires from 141 clinical services were returned. Regarding the key targets specified in the BHIVA monitoring guidelines, 97% of patients on antiretroviral therapy (ART) had had their viral load measured in the last 9 months, or 15 months if on a protease inhibitor, and 94% had had all medications recorded in the last 15 months. Only 67% of patients on ART without cardiovascular disease (CVD) had had a 10-year CVD risk calculated in the last 3 years. It was reported that 80% and 92% had had their smoking status documented in the last 2 years and blood pressure checked in the last 15 months, respectively. HIV services had communicated with the general practitioners of 90% of consenting individuals, but consulted electronic primary care records for only 10%. CONCLUSIONS: Nationally, targets were met for viral load and blood pressure monitoring but not for CVD risk assessment, smoking status documentation and recording of comedication. There was variable performance in relation to other outcomes; adherence and laboratory measurements were carried out more regularly than lifestyle and wellbeing assessments.

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.

Level of agreement between frequently used cardiovascular risk calculators in people living with HIV.

OBJECTIVES: The aim of the study was to describe agreement between the QRISK2, Framingham and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cardiovascular disease (CVD) risk calculators in a large UK study of people living with HIV (PLWH). METHODS: PLWH enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study without a prior CVD event were included in this study. QRISK2, Framingham CVD and the full and reduced D:A:D CVD scores were calculated; participants were stratified into 'low' (< 10%), 'intermediate' (10-20%) and 'high' (> 20%) categories for each. Agreement between scores was assessed using weighted kappas and Bland-Altman plots. RESULTS: The 730 included participants were predominantly male (636; 87.1%) and of white ethnicity (645; 88.5%), with a median age of 53 [interquartile range (IQR) 49-59] years. The median calculated 10-year CVD risk was 11.9% (IQR 6.8-18.4%), 8.9% (IQR 4.6-15.0%), 8.5% (IQR 4.8-14.6%) and 6.9% (IQR 4.1-11.1%) when using the Framingham, QRISK2, and full and reduced D:A:D scores, respectively. Agreement between the different scores was generally moderate, with the highest level of agreement being between the Framingham and QRISK2 scores (weighted kappa = 0.65) but with most other kappa coefficients in the 0.50-0.60 range. CONCLUSIONS: Estimates of predicted 10-year CVD risk obtained with commonly used CVD risk prediction tools demonstrate, in general, only moderate agreement among PLWH in the UK. While further validation with clinical endpoints is required, our findings suggest that care should be taken when interpreting any score alone.

Depression, lifestyle factors and cognitive function in people living with HIV and comparable HIV-negative controls.

OBJECTIVES: We investigated whether differences in cognitive performance between people living with HIV (PLWH) and comparable HIV-negative people were mediated or moderated by depressive symptoms and lifestyle factors. METHODS: A cross-sectional study of 637 'older' PLWH aged ≥ 50 years, 340 'younger' PLWH aged < 50 years and 276 demographically matched HIV-negative controls aged ≥ 50 years enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study was performed. Cognitive function was assessed using a computerized battery (CogState). Scores were standardized into Z-scores [mean = 0; standard deviation (SD) = 1] and averaged to obtain a global Z-score. Depressive symptoms were evaluated via the Patient Health Questionnaire (PHQ-9). Differences between the three groups and the effects of depression, sociodemographic factors and lifestyle factors on cognitive performance were evaluated using median regression. All analyses accounted for age, gender, ethnicity and level of education. RESULTS: After adjustment for sociodemographic factors, older and younger PLWH had poorer overall cognitive scores than older HIV-negative controls (P < 0.001 and P = 0.006, respectively). Moderate or severe depressive symptoms were more prevalent in both older (27%; P < 0.001) and younger (21%; P < 0.001) PLWH compared with controls (8%). Depressive symptoms (P < 0.001) and use of hashish (P = 0.01) were associated with lower cognitive function; alcohol consumption (P = 0.02) was associated with better cognitive scores. After further adjustment for these factors, the difference between older PLWH and HIV-negative controls was no longer significant (P = 0.08), while that between younger PLWH and older HIV-negative controls remained significant (P = 0.01). CONCLUSIONS: Poorer cognitive performances in PLWH compared with HIV-negative individuals were, in part, mediated by the greater prevalence of depressive symptoms and recreational drug use reported by PLWH.

HIV coinfection among persons diagnosed with hepatitis B in England in 2008-2014.

OBJECTIVES: The aim of the study was to estimate HIV prevalence among persons with hepatitis B virus (HBV) infection in England and to examine associated risk factors. METHODS: Persons aged ≥ 15 years with an HBV surface antigen (HBsAg) test reported to Public Health England (PHE) sentinel surveillance during 2008-2014 were linked to the PHE national HIV/AIDS database. Coinfection was defined as an HIV diagnosis prior to, or within 6 months following, a positive HBsAg test. RESULTS: During 2008-2014, 2 149 933 persons were tested for HBsAg and 3.9% (1129 of 28 789) of HBsAg-positive persons were HIV positive. The probable route of HIV infection was heterosexual exposure for 95.3% of female patients and 32.3% of male patients, with 61.5% of male patients reporting sex between men. Among African-born coinfected persons, 84% probably acquired HIV there. Predictors of HIV positivity included older age [adjusted odds ratio (aOR) 1.1] and being of black ethnicity (aOR 15.5 for males; aOR 16.4 for females) or being male and of white ethnicity (aOR 8.2) compared with being female and of white ethnicity. HIV coinfection was more likely when HBV was diagnosed in sexual health (aOR 55.0), specialist liver (aOR 6.7), emergency department (aOR 5.3) and renal services (aOR 2.8) compared with general practice. Most (60.4%; 682 of 1129) coinfected persons were diagnosed with HIV infection > 6 months before HBV diagnosis. CONCLUSIONS: Persons testing positive for HBsAg had a low HIV infection rate and fell largely into two groups: those of black ethnicity with probable Africa-acquired infections and white men who have sex with men (MSM) with probable UK-acquired infections. Findings reinforce existing recommendations to sustain and improve both HBV testing of migrants from HBV-prevalent countries and vaccination among HIV-positive MSM. Findings also support blood-borne virus testing in sexual health services and emergency departments.

High-risk behaviours, and their associations with mental health, adherence to antiretroviral therapy and HIV parameters, in HIV-positive men who have sex with men.

OBJECTIVES: To investigate the patterns and frequency of multiple risk behaviours (alcohol, drugs, smoking, higher risk sexual activity) among men who have sex with men (MSM) living with HIV. METHODS: Cross sectional study. RESULTS: 147 out of 819 HIV-positive MSM exhibited a high-risk phenotype (defined as >3 of smoking, excess alcohol, sexually transmitted infection and recent recreational drug use). This phenotype was associated with younger age, depressive symptoms and <90% adherence in multivariable logistic regression. CONCLUSION: In a cohort of MSM, a small, but significant proportion exhibited multiple concurrent risk behaviours.

A systematic review of risk of HIV transmission through biting or spitting: implications for policy.

OBJECTIVES: The perceived threat of HIV transmission through spitting and biting is evidenced by the increasing use of "spit hoods" by Police Forces in the UK. In addition, a draft parliamentary bill has called for increased penalties for assaults on emergency workers, citing the risk of communicable disease transmission as one justification. We aimed to review literature relating to the risk of HIV transmission through biting or spitting. METHODS: A systematic literature search was conducted using Medline, Embase and Northern Lights databases and conference websites using search terms relating to HIV, AIDS, bite, spit and saliva. Inclusion and exclusion criteria were applied to identified citations. We classified plausibility of HIV transmission as low, medium, high or confirmed based on pre-specified criteria. RESULTS: A total of 742 abstracts were reviewed, yielding 32 articles for full-text review and 13 case reports/series after inclusion and exclusion criteria had been applied. There were no reported cases of HIV transmission related to spitting and nine cases identified following a bite, in which the majority occurred between family (six of nine), in fights involving serious wounds (three of nine), or to untrained first-aiders placing fingers in the mouth of someone having a seizure (two of nine). Only four cases were classified as highly plausible or confirmed transmission. None related to emergency workers and none were in the UK. CONCLUSIONS: There is no risk of transmitting HIV through spitting, and the risk through biting is negligible. Post-exposure prophylaxis is not indicated after a bite in all but exceptional circumstances. Policies to protect emergency workers should be developed with this evidence in mind.

The use of funnel plots with regression as a tool to visually compare HIV treatment outcomes between centres adjusting for patient characteristics and size: a UK Collaborative HIV Cohort study.

OBJECTIVES: A measure used for assessing the effectiveness of HIV care and comparing clinical centres is the proportion of people starting antiretroviral therapy (ART) with viral suppression (VS) after 1 year. We propose a method that adjusts for patients' demographic characteristics, and visually compares this measure between different sites accounting for centre size. METHODS: We analysed viral load measurements for UK Collaborative HIV Cohort (UK CHIC) patients starting ART between 2006 and 2013. We used logistic regression to estimate the proportion with VS after 1 year of ART adjusted for patient mix (in terms of age and a combined gender/ethnicity/acquisition mode variable) and calendar year. We compared outcomes between centres using funnel plots which account for centre size. RESULTS: The overall proportion of the cohort with VS 1 year after starting ART was 90% and increased from 83% to 93% between 2006 and 2013. VS was lower in younger individuals. White men who have sex with men (MSM) had the highest (94%), and black African (81%) and white (82%) heterosexual women the lowest proportions achieving VS. Comparing the unadjusted funnel plot with the adjusted, there were movements of some centres from outside to inside the 95% contour limits, which was largely explained by the patient mix of these centres. CONCLUSIONS: VS 1 year after ART start was associated with demographic characteristics and centre size; therefore, to compare the performances of centres, adjustment for these factors is required. Adjusted funnel plot is an effective tool which accounts for both the demographic characteristics and the centre size. Social factors, rather than treatment decisions within the control of the centres, may drive differences in outcomes.

Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate.

OBJECTIVES: Tenofovir disoproxil fumarate (TDF) is widely used in the treatment or prevention of HIV and hepatitis B infection. TDF may cause renal tubulopathy in a small proportion of recipients. We aimed to study the risk factors for developing severe renal tubulopathy. METHODS: We conducted an observational cohort study with retrospective identification of cases of treatment-limiting tubulopathy during TDF exposure. We used multivariate Poisson regression analysis to identify risk factors for tubulopathy, and mixed effects models to analyse adjusted estimated glomerular filtration rate (eGFR) slopes. RESULTS: Between October 2002 and June 2013, 60 (0.4%) of 15,983 patients who had received TDF developed tubulopathy after a median exposure of 44.1 (IQR 20.4, 64.4) months. Tubulopathy cases were predominantly male (92%), of white ethnicity (93%), and exposed to antiretroviral regimens that contained boosted protease inhibitors (PI, 90%). In multivariate analysis, age, ethnicity, CD4 cell count and use of didanosine or PI were significantly associated with tubulopathy. Tubulopathy cases experienced significantly greater eGFR decline while receiving TDF than the comparator group (-6.60 [-7.70, -5.50] vs. -0.34 [-0.43, -0.26] mL/min/1.73 m2/year, p < 0.0001). CONCLUSIONS: Older age, white ethnicity, immunodeficiency and co-administration of ddI and PI were risk factors for tubulopathy in patients who received TDF-containing antiretroviral therapy. The presence of rapid eGFR decline identified TDF recipients at increased risk of tubulopathy.

Lopinavir and atazanavir in pregnancy: comparable infant outcomes, virological efficacies and preterm delivery rates.

OBJECTIVES: The aim of the study was to identify differences in infant outcomes, virological efficacy, and preterm delivery (PTD) outcome between women exposed to lopinavir/ritonavir (LPV/r) and those exposed to atazanavir/ritonavir (ATV/r). METHODS: A retrospective case note review was carried out. The case notes of 493 women who conceived while on LPV/r or ATV/r or initiated LPV/r or ATV/r during pregnancy and who delivered between 1 September 2007 and 30 August 2012 were reviewed. Data collected included demographics, antiretroviral use, HIV markers, and pregnancy and infant outcomes. Infant outcomes, virological efficacies and PTD rates for LPV/r and ATV/r were compared. RESULTS: A total of 306 women received LPV/r (82 conceiving while on the drug and 224 commencing it post-conception) and 187 received ATV/r (96 conceiving while on the drug and 91 commencing it post-conception). Comparing the two protease inhibitors (PIs), viral suppression rates were similar and, in women starting antiretroviral therapy (ART) post-conception, the median times to first undetectable HIV viral load were not significantly different (P = 0.64). PTD rates did not differ by therapy overall (ATV/r, 13%; LPV/r, 14%) or when considering the timing of first exposure (conceiving on ART, P = 0.81; commencing ART in pregnancy, P = 0.08). Poor fetal outcomes were very uncommon. There were two transmissions, giving a mother-to-child transmission (MTCT) rate of 0.4% (95% confidence interval 0.05-1.5%). CONCLUSIONS: Both ART regimens were well tolerated and successful in preventing MTCT. No significant differences in tolerability or in pregnancy or infant outcomes were observed, which supports the provision of a choice of PI in pregnancy.

Time to initiation of antiretroviral therapy in HIV-infected patients diagnosed with an opportunistic disease: a cohort study.

OBJECTIVES: The aim of the study was to identify factors associated with the time between opportunistic disease (OD) diagnosis and antiretroviral therapy (ART) initiation in HIV-infected patients presenting for care with an OD, and to evaluate the outcomes associated with any delay. METHODS: A multicentre cohort study was undertaken in London, Paris and Lille/Tourcoing. The medical records of patients diagnosed from 2002 to 2012 were reviewed. RESULTS: A total of 437 patients were enrolled in the study: 70% were male, the median age was 40 years, 42% were from sub-Saharan Africa, 68% were heterosexual, the median CD4 count was 40 cells/µL, and the most common ODs were Pneumocystis pneumonia (37%), tuberculosis (24%), toxoplasmosis (12%) and Kaposi's sarcoma (11%). Of these patients, 400 (92%) started ART within 24 weeks after HIV diagnosis, with a median time from OD diagnosis to ART initiation of 30 [interquartile range (IQR) 16-58] days. Patients diagnosed between 2009 and 2012 had a shorter time to ART initiation than those diagnosed in earlier years [hazard ratio (HR) 2.07; 95% confidence interval (CI) 1.58-2.72]. Factors associated with a longer time to ART initiation were a CD4 count ≥ 200 cells/µL (HR 0.30; 95% CI 0.20-0.44), tuberculosis (HR 0.40; 95% CI 0.30-0.55) and diagnosis in London (HR 0.62; 95% CI 0.48-0.80). Patients initiating 'deferred' ART (by ≥ 30 days) exhibited no difference in disease progression or immunovirological response compared with patients who had shorter times to ART initiation. Patients in the 'deferred' group were less likely to have ART modifications (HR 0.69; 95% CI 0.48-1.00) and had shorter in-patient stays (mean 14.2 days shorter; 95% CI 8.9-19.5 days) than patients in the group whose ART was not deferred. CONCLUSIONS: The time between OD diagnosis and ART initiation remains heterogeneous and relatively long, particularly in individuals with a high CD4 count or tuberculosis or those diagnosed in London. Deferring ART was associated with fewer ART modifications and shorter in-patient stays.

Increased risk of cardiovascular disease (CVD) with age in HIV-positive men: a comparison of the D:A:D CVD risk equation and general population CVD risk equations.

OBJECTIVES: The aim of the study was to statistically model the relative increased risk of cardiovascular disease (CVD) per year older in Data collection on Adverse events of anti-HIV Drugs (D:A:D) and to compare this with the relative increased risk of CVD per year older in general population risk equations. METHODS: We analysed three endpoints: myocardial infarction (MI), coronary heart disease (CHD: MI or invasive coronary procedure) and CVD (CHD or stroke). We fitted a number of parametric age effects, adjusting for known risk factors and antiretroviral therapy (ART) use. The best-fitting age effect was determined using the Akaike information criterion. We compared the ageing effect from D:A:D with that from the general population risk equations: the Framingham Heart Study, CUORE and ASSIGN risk scores. RESULTS: A total of 24 323 men were included in analyses. Crude MI, CHD and CVD event rates per 1000 person-years increased from 2.29, 3.11 and 3.65 in those aged 40-45 years to 6.53, 11.91 and 15.89 in those aged 60-65 years, respectively. The best-fitting models included inverse age for MI and age + age(2) for CHD and CVD. In D:A:D there was a slowly accelerating increased risk of CHD and CVD per year older, which appeared to be only modest yet was consistently raised compared with the risk in the general population. The relative risk of MI with age was not different between D:A:D and the general population. CONCLUSIONS: We found only limited evidence of accelerating increased risk of CVD with age in D:A:D compared with the general population. The absolute risk of CVD associated with HIV infection remains uncertain.