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1.
HIV Med ; 21(9): 588-598, 2020 10.
Article in English | MEDLINE | ID: mdl-32776431

ABSTRACT

OBJECTIVES: We report the frequency of previous HIV testing at baseline in men who have sex with men (MSM) who enrolled in an HIV self-testing (HIVST) randomized controlled trial [an HIV self-testing public health intervention (SELPHI)]. METHODS: Criteria for enrolment were age ≥ 16 years, being a man (including trans men) who ever had anal intercourse (AI) with a man, not being known to be HIV positive and having consented to national HIV database linkage. Using online survey baseline data (2017-2018), we assessed associations with never having tested for HIV and not testing in the previous 6 months, among men who reported at least two recent condomless AI (CAI) partners. RESULTS: A total of 10 111 men were randomized; the median age was 33 years [interquartile range (IQR) 26-44 years], 89% were white, 20% were born outside the UK, 0.8% were trans men, 47% were degree educated, and 8% and 4% had ever used and were currently using pre-exposure prophylaxis (PrEP), respectively. In the previous 3 months, 89% reported AI and 72% reported CAI with at least one male partner. Overall, 17%, 33%, 54%, and 72% had tested for HIV in the last 3 months, 6 months, 12 months and 2 years, respectively; 13% had tested more than 2 years ago and 15% had never tested. Among 3972 men reporting at least two recent CAI partners, only 22% had tested in the previous 3 months. Region of residence and education level were independently associated with recent HIV testing. Among current PrEP users, 15% had not tested in the previous 6 months. CONCLUSIONS: Most men in SELPHI, particularly those reporting at least two CAI partners and current PrEP users, were not testing in line with current UK recommendations. The results of the trial will inform whether online promotion of HIVST addresses ongoing testing barriers.


Subject(s)
HIV Infections/diagnosis , HIV Testing/methods , Homosexuality, Male/statistics & numerical data , Pre-Exposure Prophylaxis/statistics & numerical data , Sexual Behavior/classification , Adult , HIV Infections/epidemiology , HIV Infections/prevention & control , Humans , Male , Public Health , Self-Testing , Sexual Behavior/statistics & numerical data , Sexual Partners , United Kingdom/epidemiology , Unsafe Sex/statistics & numerical data
2.
HIV Med ; 21(3): 189-197, 2020 03.
Article in English | MEDLINE | ID: mdl-31821698

ABSTRACT

OBJECTIVES: SELPHI (HIV Self-Testing Public Health Intervention) is the largest randomized controlled trial (RCT) of HIV self-testing (HIVST) in a high-income setting to date, and has recruited 10 000 men who have sex with men (cis- and transgender) and transgender women who have sex with men. This qualitative substudy aimed to explore how those utilizing self-tests experience HIVST and the implications for further intervention development and scale-up. This is the first qualitative study in Europe investigating experiences of HIVST among intervention users, and the first globally examining the experience of using blood-based HIVST. METHODS: Thirty-seven cisgender MSM SELPHI participants from across England and Wales were purposively recruited to the substudy, in which semi-structured interviews were used to explore testing history, HIVST experiences and intervention preferences. Interviews were audio-recorded, transcribed and analysed through a framework analysis. RESULTS: Men accessed the intervention because HIVST reduced barriers related to convenience, stigma and privacy concerns. Emotional responses had direct links to acceptability. Supportive intervention components increased engagement with testing and addressed supportive concerns. HIVST facilitated more frequent testing, with the potential to reduce sexually transmitted infection (STI) screening frequency. Substudy participants with an HIV-positive result (n = 2) linked to care promptly and reported very high acceptability. Minor adverse outcomes (n = 2; relationship discord and fainting) did not reduce acceptability. Ease of use difficulties were with the lancet and the test processing stage. CONCLUSIONS: Intervention components shaped acceptability, particularly in relation to overcoming a perceived lack of support. The intervention was broadly acceptable and usable; participants expressed an unexpected degree of enthusiasm for HIVST, including those with HIV-positive results and individuals with minor adverse outcomes.


Subject(s)
Early Detection of Cancer/methods , HIV Infections/diagnosis , Homosexuality, Male/statistics & numerical data , Transgender Persons/statistics & numerical data , Adolescent , Adult , Developed Countries , England , Evaluation Studies as Topic , Female , Humans , Interviews as Topic , Male , Patient Acceptance of Health Care , Reagent Kits, Diagnostic , Self-Testing , Wales , Young Adult
3.
AIDS Behav ; 24(6): 1793-1806, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31782068

ABSTRACT

The aim of this study is to investigate five hypothesized mechanisms of causation between depression and condomless sex with ≥ 2 partners (CLS2+) among gay, bisexual, and other men who have sex with men (GBMSM), involving alternative roles of self-efficacy for sexual safety and recreational drug use. Data were from the AURAH cross-sectional study of 1340 GBMSM attending genitourinary medicine clinics in England (2013-2014). Structural equation modelling (SEM) was used to investigate which conceptual model was more consistent with the data. Twelve percent of men reported depression (PHQ-9 ≥ 10) and 32% reported CLS2+ in the past 3 months. AURAH data were more consistent with the model in which depression was considered to lead to CLS2+ indirectly via low self-efficacy for sexual safety (indirect Beta = 0.158; p < 0.001) as well as indirectly via higher levels of recreational drug use (indirect Beta = 0.158; p < 0.001). SEM assists in understanding the relationship between depression and CLS among GBMSM.


Subject(s)
Depression , HIV Infections , Sexual Behavior , Sexual and Gender Minorities , Unsafe Sex , Adolescent , Adult , Condoms , Cross-Sectional Studies , Depression/epidemiology , England/epidemiology , Female , Homosexuality, Male , Humans , Latent Class Analysis , Male , Middle Aged , Risk-Taking , Sexual Partners , Young Adult
4.
HIV Med ; 19(3): 184-194, 2018 03.
Article in English | MEDLINE | ID: mdl-29230953

ABSTRACT

OBJECTIVES: To investigate factors that predict speed of recovery and long-term CD4 cell count in HIV-1 seroconverters initiating combination antiretroviral therapy (cART), and to quantify the influence of very early treatment initiation. We make use of all pre-treatment CD4 counts, because analyses using only a single observation at initiation may be subject to biases. METHODS: We used data from the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) multinational cohort collaboration of HIV-1 seroconverters. We analysed pre- and post-treatment data of patients with seroconversion dates estimated January 2003-March 2014 (n = 7600 for primary analysis) using a statistical model in which the characteristics of recovery in CD4 counts are determined by multiple predictive factors. Secondary analyses were performed incorporating uncertainty in the exact timing of seroconversion to allow more precise estimation of the benefit of very early treatment initiation. RESULTS: 'True' CD4 count at cART initiation was the strongest predictor of CD4 count beyond 3 years on cART. Allowing for lack of complete certainty in the date of seroconversion, CD4 recovery was more rapid for patients in whom treatment was initiated within 4 months. For a given CD4 count, higher viral load (VL) at initiation was strongly associated with higher post-treatment CD4 recovery. For other patient and drug characteristics, associations with recovery were statistically significant but small in magnitude. CONCLUSIONS: CD4 count at cART initiation is the most important factor in predicting post-treatment recovery, but VL provides substantial additional information. If cART is initiated in the first 4 months following seroconversion, recovery of CD4 counts appears to be more rapid.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/immunology , HIV-1/immunology , CD4 Lymphocyte Count , Female , HIV Infections/drug therapy , Humans , Male , Models, Statistical , Seroconversion , Treatment Outcome , Viral Load
5.
HIV Med ; 18(2): 89-103, 2017 02.
Article in English | MEDLINE | ID: mdl-27385511

ABSTRACT

OBJECTIVES: An increasing proportion of people living with HIV are older adults, who may require specialized care. Adverse physical and psychological effects of HIV infection may be greatest among older people or those who have lived longer with HIV. METHODS: The ASTRA study is a cross-sectional questionnaire study of 3258 HIV-diagnosed adults (2248 men who have sex with men, 373 heterosexual men and 637 women) recruited from UK clinics in 2011-2012. Associations of age group with physical symptom distress (significant distress for at least one of 26 symptoms), depression and anxiety symptoms (scores ≥ 10 on PHQ-9 and GAD-7, respectively), and health-related functional problems (problems on at least one of three domains of the Euroqol 5D-3L)) were assessed, adjusting for time with diagnosed HIV infection, gender/sexual orientation and ethnicity. RESULTS: The age distribution of participants was: < 30 years, 5%; 30-39 years, 23%; 40-49 years, 43%; 50-59 years, 22%; and ≥ 60 years, 7%. Overall prevalences were: physical symptom distress, 56%; depression symptoms, 27%; anxiety symptoms, 22%; functional problems, 38%. No trend was found in the prevalence of physical symptom distress with age [adjusted odds ratio (OR) for trend across age groups, 0.96; 95% confidence interval (CI) 0.89, 1.04; P = 0.36]. The prevalence of depression and anxiety symptoms decreased with age [adjusted OR 0.86 (95% CI 0.79, 0.94; P = 0.001) and adjusted OR 0.85 (95% CI 0.77, 0.94; P = 0.001), respectively], while that of functional problems increased (adjusted OR 1.28; 95% CI 1.17, 1.39; P < 0.001). In contrast, a longer time with diagnosed HIV infection was strongly and independently associated with a higher prevalence of symptom distress, depression symptoms, anxiety symptoms, and functional problems (P < 0.001 for trends, adjusted analysis). CONCLUSIONS: Among people living with HIV, although health-related functional problems were more common with older age, physical symptom distress was not, and mental health was more favourable. These results suggest that a longer time with diagnosed HIV infection, rather than age, is the dominating factor contributing to psychological morbidity and lower quality of life.


Subject(s)
Anxiety/epidemiology , Depression/epidemiology , HIV Infections/pathology , HIV Infections/psychology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Surveys and Questionnaires , Time Factors , United Kingdom , Young Adult
6.
HIV Med ; 18(7): 463-473, 2017 08.
Article in English | MEDLINE | ID: mdl-28004523

ABSTRACT

OBJECTIVES: The aim of the study was to assess, among people living with HIV, knowledge of their latest HIV viral load (VL) and CD4 count. METHODS: Agreement between self-report and clinic record was assessed among 2771 HIV-diagnosed individuals on antiretroviral treatment (ART) in the UK Antiretrovirals, Sexual Transmission Risk and Attitudes Study (2011-2012). A confidential self-completed questionnaire collected information on demographic, socioeconomic, HIV-related and health-related factors. Participants were asked to self-report their latest VL [undetectable (≤ 50 copies/mL), detectable (> 50 copies/mL) or "don't know"] and CD4 count (< 200, 200-350, 351-500 or > 500 cells/µL, or "don't know"). Latest clinic-recorded VL and CD4 count were documented. RESULTS: Of 2678 participants on ART, 434 (16.2%) did not accurately report whether their VL was undetectable. Of 2334 participants with clinic-recorded VL ≤ 50 copies/mL, 2061 (88.3%) correctly reported undetectable VL; 49 (2.1%) reported detectable VL; 224 (9.6%) did not know their VL. Of 344 participants with clinic-recorded VL > 50 copies/mL, 183 (53.2%) correctly reported detectable VL; 76 (22.1%) reported undetectable VL; 85 (24.7%) did not know their VL. Of 2137 participants who reported undetectable VL, clinic-recorded VL was ≤ 50 copies/mL for 2061 (96.4%) and <1000 copies/mL for 2122 (99.3%). In analyses adjusted for gender/sexual orientation, ethnicity, age and time since starting ART, factors strongly associated with inaccurate self-report of VL (including "don't know") included socioeconomic disadvantage [prevalence ratio (95% CI) for "not" vs. "always" having enough money for basic needs: 2.4 (1.9, 3.1)], poor English fluency [3.5 (2.4, 5.1) vs. UK born], nondisclosure of HIV status [1.7 (1.3, 2.1)], ART nonadherence [2.1 (1.7, 2.7) for three or more missed doses vs. none in the past 2 weeks] and depressive symptoms (PHQ-9 score ≥ 10) [1.9 (1.6, 2.2)]. Overall, 612 (22.9%) of 2667 participants on ART did not accurately self-report whether or not their CD4 count was ≤ 350 cells/µL. CONCLUSIONS: There is a high level of accuracy of a self-report of undetectable VL in people on ART in the UK. Overall, accurate knowledge of personal VL level varied according to demographic, socioeconomic, HIV-related and health-related factors. Active identification of people who may benefit from increased levels of support and engagement in care is important.


Subject(s)
Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/virology , Self Report , Viral Load , Adult , Aged , CD4 Lymphocyte Count , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Surveys and Questionnaires , United Kingdom , Young Adult
7.
HIV Med ; 17(2): 124-32, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26186609

ABSTRACT

OBJECTIVES: The aim of the study was to investigate the relationship between self-reported antiretroviral therapy (ART) adherence and virological outcomes in the multinational Strategies for Management of Antiretroviral Therapy (SMART) study. METHODS: Eligible participants were from the continuous ART arm and had at least one viral load (VL) ≤ 50 HIV-1 RNA copies/mL and a subsequent VL value (VL pair). Self-reported adherence was measured at each visit using a five-point Likert scale which employed a 7-day recall. High adherence was defined as taking 'all pills every day' (level 1) for every regimen component; all others had suboptimal adherence (levels 2 - 5). In individuals with VL suppression (≤ 50 copies/mL), the association between adherence (at the time of VL suppression) and VL rebound (> 200 copies/mL at next visit) was assessed using multivariable logistic regression with generalized estimating equations. RESULTS: A total of 10 761 sets of VL pairs from 1986 participants were included in the study. For 1220 (11%) VL pairs, adherence was suboptimal. For 507 VL pairs (5%), VL rebound occurred. The risk of rebound generally increased as adherence decreased: 4.2% for level 1, 7.7% for level 2, 16.3% for level 3, 9.4% for level 4 and 12.9% for level 5. In multivariable analysis, suboptimal adherence at the time of suppression was associated with a 50% increased odds of experiencing subsequent VL rebound [odds ratio (OR) 1.51; 95% confidence interval (CI) 1.19-1.92; P = 0.0023], compared with high adherence. CONCLUSIONS: Self-reported suboptimal adherence in people with VL suppression is associated with an increased risk of VL rebound. Our findings highlight the importance of continued adherence counselling, even in people with VL suppression, and to ensure that people with HIV infection maintain excellent adherence in order to minimize the risk of VL rebound.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/immunology , HIV-1/immunology , Medication Adherence/statistics & numerical data , Adult , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Follow-Up Studies , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/physiology , Humans , Middle Aged , Predictive Value of Tests , Risk Factors , Self Report , Time Factors , Viral Load
8.
HIV Med ; 16 Suppl 1: 64-76, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25711325

ABSTRACT

OBJECTIVES: A proportion of HIV-positive people have condomless sex. Antiretroviral treatment (ART) reduces infectiousness, but a substantial proportion of HIV-diagnosed people are not yet on ART. We describe baseline self-reported risk behaviours in ART-naïve Strategic Timing of AntiRetroviral Treatment (START) trial participants. METHODS: All START participants completed a risk behaviour questionnaire. Data were collected on sociodemographics, lifestyle factors, health and wellbeing status and clinical status. Recent sexual behaviour and HIV transmission beliefs in the context of ART were also assessed. The primary interest was in condomless sex with serodifferent partners (CLS-D) in the past two months. RESULTS: A total of 4601 of 4685 HIV-positive participants (98%) completed the questionnaire [2559 men who have sex with men (MSM), 803 heterosexual men and 1239 women]. Region of recruitment was Europe/Israel, 33%; South America/Mexico, 25%; Africa, 22%; other, 21%. Median age was 36 years [interquartile range (IQR) 29, 44 years]. Forty-five per cent reported white ethnicity and 31% black ethnicity. Two per cent had HIV viral load < 50 HIV-1 RNA copies/mL. Seventeen per cent (767 of 4601) reported CLS-D; 20% of MSM compared with 10% of heterosexual men and 14% of women. MSM were also more likely to report multiple CLS-D partners. Possible risk limitation measures (reported by more than half of those who had CLS-D) were seropositioning (receptive anal CLS-D only) or withdrawal (insertive anal CLS-D always without ejaculation). CLS-D was more commonly reported by participants from South America/Mexico and North America compared with Europe; among heterosexual men and women CLS-D was also more commonly reported among participants from Africa compared with Europe. Knowledge of ART impact on transmission risk was low. CONCLUSIONS: A substantial minority recruited to the START study reported CLS-D at baseline. CLS-D reporting was higher in MSM than heterosexuals and varied significantly according to region of recruitment. A substantial proportion of MSM reporting CLS-D appear to take transmission risk limitation measures.


Subject(s)
Disease Transmission, Infectious , HIV Infections/transmission , Unsafe Sex , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Surveys and Questionnaires , Young Adult
9.
Infection ; 42(4): 757-62, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24902520

ABSTRACT

ATRIPLA is licensed for use only in HIV-positive persons whose viral loads <50 for ≥ 3 months. We investigated the use of ATRIPLA as first-line antiretroviral therapy (ART) in EuroSIDA using a web-based survey performed in Autumn 2012. 96/112 clinics (85.7 %) completed the survey. Recommendations when initiating first-line ART was TRUVADA plus efavirenz in 36 (37.5 %), ATRIPLA in 35 (36.5 %), a different first-line regimen in 12 clinics (12.5 %), and no recommendation in 7 clinics (7.3 %). ATRIPLA was commonest in Northern (15/21 clinics; 71.4 %), and least common in Eastern Europe (2/31 clinics; 6.5 %; p < 0.0001). Over one-third of the participating clinics in this survey were using ATRIPLA as first-line antiretroviral therapy, despite EMA recommendations.


Subject(s)
Adenine/analogs & derivatives , Anti-HIV Agents/therapeutic use , Deoxycytidine/analogs & derivatives , Drug Utilization , HIV Infections/drug therapy , Organophosphonates/therapeutic use , Oxazines/therapeutic use , Adenine/therapeutic use , Adult , Cohort Studies , Data Collection , Deoxycytidine/therapeutic use , Drug Combinations , Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination , Europe , Female , Humans , Male , Prospective Studies
10.
HIV Med ; 15(10): 595-603, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24840675

ABSTRACT

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.


Subject(s)
Coronary Disease/etiology , HIV Infections/complications , Myocardial Infarction/etiology , Stroke/etiology , Adult , Age Factors , Aged , Anti-HIV Agents/adverse effects , HIV Infections/drug therapy , Humans , Male , Middle Aged , Prospective Studies , Regression Analysis , Risk Factors
11.
Euro Surveill ; 18(48): 20647, 2013 Nov 28.
Article in English | MEDLINE | ID: mdl-24308982

ABSTRACT

The aim of this review is to summarise the evidence on the population-level effect of antiretroviral therapy (ART) in preventing HIV infections, and to discuss potential implications in the European context of recommending starting ART when the CD4 count is above 350 cells/mm3. The ability of ART to reduce the risk of HIV transmission has been reported in observational studies and in a randomised controlled trial (HPTN 052), in which ART initiation reduced HIV transmission by 96% within serodiscordant couples. As yet, there is no direct evidence for such an effect among men having sex with men or people who inject drugs. HPTN 052 led international organisations to develop recommendations with a higher CD4 threshold for ART initiation. However, there remains a lack of strong evidence of clinical benefit for HIV-positive individuals starting ART with CD4 count above 350 cells/mm3. The main goal of ART provision should be to increase ART coverage for all those in need, based on the current guidelines, and the offer of ART to those who wish to reduce infectivity; increased HIV testing is therefore a key requirement. Other proven prevention means such as condom use and harm reduction for people who inject drugs remain critical.


Subject(s)
Anti-Retroviral Agents/therapeutic use , HIV Infections/prevention & control , HIV Infections/transmission , Adult , CD4 Lymphocyte Count , Eligibility Determination , Europe , Female , HIV Infections/drug therapy , HIV-1 , Humans , Male , Middle Aged , Sexual Partners
12.
HIV Med ; 13(1): 73-8, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22106827

ABSTRACT

OBJECTIVES: Current British HIV Association (BHIVA) guidelines recommend that all patients with a CD4 count <350 cells/µL are offered highly active antiretroviral therapy (HAART). We identified risk factors for delayed initiation of HAART following a CD4 count <350 cells/µL. METHODS: All adults under follow-up in 2008 who had a first confirmed CD4 count <350 cells/µL from 2004 to 2008, who had not initiated treatment and who had >6 months of follow-up were included in the study. Characteristics at the time of the low CD4 cell count and over follow-up were compared to identify factors associated with delayed HAART uptake. Analyses used proportional hazards regression with fixed (sex/risk group, age, ethnicity, AIDS, baseline CD4 cell count and calendar year) and time-updated (frequency of CD4 cell count measurement, proportion of CD4 counts <350 cells/µL, latest CD4 cell count, CD4 percentage and viral load) covariates. RESULTS: Of 4871 patients with a confirmed low CD4 cell count, 436 (8.9%) remained untreated. In multivariable analyses, those starting HAART were older [adjusted relative hazard (aRH)/10 years 1.15], were more likely to be female heterosexual (aRH 1.13), were more likely to have had AIDS (aRH 1.14), had a greater number of CD4 measurements < 350 cells/µL (aRH/additional count 1.18), had a lower CD4 count over follow-up (aRH/50 cells/µL higher 0.57), had a lower CD4 percentage (aRH/5% higher 0.90) and had a higher viral load (aRH/log(10) HIV-1 RNA copies/ml higher 1.06). Injecting drug users (aRH 0.53), women infected with HIV via nonsexual or injecting drug use routes (aRH 0.75) and those of unknown ethnicity (aRH 0.69) were less likely to commence HAART. CONCLUSION: A substantial minority of patients with a CD4 count < 350 cells/µL remain untreated despite its indication.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , HIV Infections/immunology , Medication Adherence , Adult , Biomarkers/analysis , CD4 Lymphocyte Count , Female , Follow-Up Studies , Humans , Male , Proportional Hazards Models , Risk Factors , United Kingdom
13.
HIV Med ; 13(5): 309-14, 2012 May.
Article in English | MEDLINE | ID: mdl-22151684

ABSTRACT

OBJECTIVES: Recent studies have shown that pre-exposure prophylaxis (PrEP) can substantially reduce the chance of acquiring HIV infection. However, PrEP efficacy has been found to be compromised in macaque studies if the challenge virus is antiretroviral therapy (ART)-resistant. Our objective was to evaluate the likelihood that a UK man who has sex with men (MSM) would be exposed to PrEP-resistant HIV in a homosexual encounter with an HIV-infectious partner. METHODS: Data from the UK Collaborative HIV Cohort (UK CHIC) study were linked to the UK HIV Drug Resistance Database for HIV-1-positive MSM patients seen between 2005 and 2008. Patients were categorized as undiagnosed; diagnosed but ART-naïve; ART-experienced and on treatment; and ART-experienced and on a treatment interruption. Considering current PrEP regimens, resistance to (a) tenofovir (TDF) alone, (b) TDF and emtricitabine (FTC), and (c) TDF or FTC was estimated. Patients without resistance tests had PrEP resistance imputed using bootstrapping and logistic regression models. RESULTS: The population-level prevalence of PrEP resistance in HIV-infectious individuals in 2008 was estimated to be 1.6, 0.9 and 4.1% for PrEP resistance definitions a, b and c, respectively. Prevalence in ART-experienced patients was highest, with negligible circulating resistance amongst ART-naïve individuals. The levels of resistance declined over the period of study. CONCLUSIONS: Our analysis indicates low levels of resistance to proposed PrEP drugs. The estimated PrEP resistance prevalence in UK HIV-infected MSM is towards the lower range of values used in simulation studies which have suggested that circulating PrEP drug resistance will have a negligible impact on PrEP efficacy at the population level.


Subject(s)
Adenine/analogs & derivatives , Anti-HIV Agents/pharmacology , Deoxycytidine/analogs & derivatives , Drug Resistance, Viral/drug effects , HIV Infections/prevention & control , HIV-1/drug effects , Homosexuality, Male , Organophosphonates/pharmacology , Adenine/administration & dosage , Adenine/pharmacology , Anti-HIV Agents/administration & dosage , Cohort Studies , Deoxycytidine/administration & dosage , Deoxycytidine/pharmacology , Drug Therapy, Combination , Emtricitabine , HIV Infections/epidemiology , HIV Infections/virology , Humans , Logistic Models , Male , Organophosphonates/administration & dosage , Prevalence , Tenofovir , United Kingdom/epidemiology , Viral Load
14.
HIV Med ; 13(1): 62-72, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21848790

ABSTRACT

BACKGROUND: Virological failure of first-generation nonnucleoside reverse transcriptase inhibitors (NNRTIs) can compromise the efficacy of etravirine as a result of the accumulation of NNRTI resistance mutations. How quickly NNRTI resistance accumulates in patients with a delayed switch from nevirapine or efavirenz despite virological failure, when these drugs are used as a component of combination antiretroviral therapy (cART), remains unclear. METHODS: The rate of NNRTI resistance accumulation was estimated in patients in EuroSIDA with at least two available genotypic resistance tests (GRTs), provided that (1) the date of the first GRT (t0) was after the date of the first virological failure (VF) of an NNRTI, and (2) patients were receiving an NNRTI and HIV RNA was >500 HIV-1 RNA copies/mL in all measurements between GRTs. RESULTS: A total of 227 patients were included in the study, contributing 467 GRT pairs. At baseline-t0, a median of 3 months after VF, 66% of patients had at least one NNRTI mutation: 103N (34%), 181C (22%) and 190A (20%) were the most common mutations. Overall, 180 additional NNRTI mutations were found to have accumulated over 295 years [1 new/1.6 years; 95% confidence interval (CI) 1.5-1.8]. The rate of accumulation was faster in the first 6 months from VF (1 new/1.1 years), and slower in patients exposed to nevirapine vs. those receiving efavirenz [relative risk (RR) 0.66; 95% CI 0.46-0.95; P=0.03]. CONCLUSIONS: There is an initial phase of rapid accumulation of NNRTI mutations close to the time of VF followed by a phase of slower accumulation. We predict that it should take approximately one year of exposure to a virologically failing first-generation NNRTI-based cART regimen to reduce etravirine activity from fully susceptible to intermediate resistant, and possibly longer in patients kept on a failing nevirapine-containing regimen.


Subject(s)
Anti-HIV Agents/therapeutic use , Benzoxazines/therapeutic use , Drug Resistance, Viral/genetics , HIV Infections/drug therapy , Mutation , Nevirapine/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , Adult , Aged , Alkynes , Cyclopropanes , DNA Mutational Analysis , Female , HIV Infections/virology , Humans , Male , Middle Aged , Prospective Studies , Viral Load , Young Adult
15.
HIV Med ; 12(10): 583-93, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21569188

ABSTRACT

OBJECTIVE: The aim of the study was to describe trends in CD4 cell counts in HIV-infected patients after initiation of combination antiretroviral therapy (cART), according to CD4 cell count at initiation (baseline), and to quantify the implications of virological failure for these trends. METHODS: Eligible participants from the UK Collaborative HIV Cohort (CHIC) were antiretroviralnaïve and started cART after 1997. Random effects were used to model CD4 cell count trends, accounting for multiple measurements within participants. We assessed whether CD4 cell count trends varied according to baseline CD4 cell count and separately in participants with and without post-cART virological failure. Effects of post-cART virological failure (>1000 HIV-1 RNA copies/mL) on subsequent CD4 cell counts were evaluated. FINDINGS: A total of 7069 participants were included in the analysis (median follow-up in all baseline CD4 cell count groups was ≥ 35 months). Among participants without virological failure ≥ 6 months after the start of cART, CD4 cell counts continued to increase up to 8 years, with little evidence that differences between baseline CD4 cell count groups diminished over time. Virological failure ≥ 6 months after the start of cART was associated with lower subsequent CD4 cell counts, with greater CD4 cell count reduction for more recent virological failure and higher viral load. CONCLUSIONS: Post-cART CD4 cell counts are strongly related to pre-cART CD4 cell counts. CD4 cell count recovery is greatest in individuals who can avoid viral loads >1000 copies/mL while on cART.


Subject(s)
Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , HIV Infections/immunology , HIV-1/immunology , RNA, Viral/immunology , Viral Load/immunology , Adult , CD4 Lymphocyte Count/trends , Cohort Studies , Drug Therapy, Combination , Female , Follow-Up Studies , HIV Infections/epidemiology , Humans , Male , Prognosis , RNA, Viral/drug effects , United Kingdom/epidemiology , Viral Load/trends
16.
Neurology ; 76(8): 693-700, 2011 Feb 22.
Article in English | MEDLINE | ID: mdl-21339496

ABSTRACT

OBJECTIVE: The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. METHODS: Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. RESULTS: The median (interquartile range) CPE score for initial cART regimen increased from 7 (5-8) in 1996-1997 to 9 (8-10) in 2000-2001 and subsequently declined to 6 (7-8) in 2006-2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤ 4, and less frequently in those with scores ≥ 10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤ 4 were independently associated with increased risk of death. CONCLUSION: Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses.


Subject(s)
Anti-HIV Agents/therapeutic use , Central Nervous System Diseases , HIV Infections/complications , HIV Infections/drug therapy , Adult , CD4 Antigens/metabolism , Central Nervous System Diseases/drug therapy , Central Nervous System Diseases/etiology , Central Nervous System Diseases/virology , Cohort Studies , Drug Therapy, Combination , Female , HIV/isolation & purification , HIV Infections/mortality , Humans , Male , Regression Analysis , Reproducibility of Results , Retrospective Studies , Sex Factors
17.
HIV Med ; 11(3): 216-24, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20002781

ABSTRACT

OBJECTIVE: The aim of the study was to assess whether a simple, routinely available measure of antiretroviral therapy (ART) adherence predicts viral rebound at the next HIV viral load (VL) measurement in virally suppressed patients. METHODS: The analysis was performed on the Royal Free HIV Cohort, London, UK. Each 'drug coverage-viral load episode' (DCVL episode) was defined as a 6-month period immediately prior to a VL < or =50 HIV-1 RNA copies/mL (time-zero), during which the patient had been continuously on HAART, with all measured VLs < or =50 copies/mL. The next VL after time-zero was used to assess whether VL rebound (defined as >200 copies/mL) had occurred. Drug coverage, our measure of adherence, was calculated as the proportion of days in the 6-month period covered by a valid prescription for at least three antiretroviral drugs. RESULTS: A total of 376 (2.4%) VL rebounds occurred in 15 660 DCVL episodes among 1632 patients. Drug coverage was 100% for 32% of episodes, 95-99% for 16% of episodes and < or =60% for 10% of episodes. The risk ratio of rebound associated with a 10% increase in drug coverage, adjusted for potential confounding variables, was 0.93 (95% confidence interval 0.88-0.98). CONCLUSIONS: Antiretroviral drug coverage assessed at the time of VL measurement in patients with undetectable VL is potentially clinically useful for predicting VL rebound at the next VL measurement.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Antiretroviral Therapy, Highly Active/statistics & numerical data , Drug Prescriptions/statistics & numerical data , HIV Infections/drug therapy , Medication Adherence/statistics & numerical data , Viral Load/statistics & numerical data , Antiretroviral Therapy, Highly Active/methods , Drug Administration Schedule , Female , HIV Infections/immunology , HIV Infections/virology , Humans , London , Male , Predictive Value of Tests , Recurrence , Statistics as Topic , Time Factors , Treatment Outcome
18.
HIV Med ; 10(1): 35-43, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19018876

ABSTRACT

OBJECTIVE: The aim of this study was to describe the relationship between age and the time to treatment discontinuation in the absence of virological failure as well as the development of specific laboratory abnormalities, in patients starting highly active antiretroviral therapy (HAART) for the first time. METHODS: Analyses included 8708 antiretroviral-naïve patients from the UK Collaborative HIV Cohort (CHIC) study who started HAART from 1998 onwards. We considered time to the first discontinuation of any drug in the initial HAART regimen for reasons other than virological failure; the association between this and age at the start of HAART was determined using proportional hazards regression after adjustment for potential confounders. The incidence of specific laboratory abnormalities in the first year after starting HAART was compared in those of different ages using multiple logistic regression. RESULTS: A total of 2650 patients discontinued at least one drug in their HAART regimen in the first year for reasons other than virological failure; after controlling for confounders, those aged < 30 years at the time of starting HAART were more likely to discontinue than those aged 30-39 years [relative hazard (RH) 1.12; 95% confidence interval (CI) 1.01, 1.24] as were those aged > or = 50 years (RH 1.14; 95% CI 1.00, 1.31). There were strong associations between greater age and raised total cholesterol, decreased haemoglobin and raised triglycerides over the first year, although the latter disappeared after adjustment for pre-HAART levels, suggesting that this finding reflected higher pre-HAART triglyceride levels in older individuals. CONCLUSIONS: Continued attempts to improve the tolerability of HAART regimens may help to sustain the good outcomes in all age groups over the longer term.


Subject(s)
Antiretroviral Therapy, Highly Active/adverse effects , HIV Infections/drug therapy , HIV-1 , Adult , Age Factors , CD4 Lymphocyte Count , Drug Administration Schedule , Female , HIV Infections/virology , Humans , Male , Middle Aged , Patient Compliance , Time Factors , Viral Load
19.
HIV Med ; 10(1): 19-27, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19018880

ABSTRACT

OBJECTIVE: More and more highly treatment-experienced patients are achieving viral suppression. However, the durability of suppression remains unclear. METHODS: Patients from Royal Free Hospital (London, UK) and JW Goethe University Hospital (Frankfurt, Germany) who had failed > or = 1 antiretroviral (ARV) regimen in all three main drug classes and > or = 3 previous ARV regimens and subsequently achieved viral load < 50 HIV-1 RNA copies/mL were included. They were followed until stopping pre-combination antiretroviral therapy, end of follow-up or viral rebound (two viral loads >400 copies/mL). RESULTS: Two hundred and forty-seven patients contributed 723 person-years and 114 viral rebounds [rate=15.8 per 100 person-years; 95% confidence interval (CI) 12.9-18.7]. More recent calendar years of viral suppression [relative risk (RR)=0.90 per year later; 95% CI 0.81-1.00; P=0.05] and greater number of ARVs in the regimen not previously failed (RR=0.78 per 1 ARV more; 95% CI 0.65-0.95; P=0.01) were associated with lower viral rebound rates. At 0-1, 1-2, 2-3 and > 3 years after achieving suppression, the rebound rates were 30.9, 9.2, 4.3 and 3.5 per 100 person-years, respectively. Compared to 0-1 years, the adjusted RRs (95% CIs) after 1-2, 2-3 and > 3 years were 0.33 (0.18-0.58), 0.21 (0.09-0.48) and 0.14 (0.06-0.33), respectively (P<0.0001). CONCLUSIONS: Although rebound rates are high, especially in the first year after viral suppression, this risk reduces substantially if highly treatment-experienced patients can maintain viral suppression.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV-1 , Adult , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Drug Administration Schedule , Female , Germany , HIV Infections/virology , Humans , London , Male , Recurrence , Time Factors , Treatment Failure , Viral Load
20.
HIV Med ; 9 Suppl 2: 6-12, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18557863

ABSTRACT

This article aims to build a picture of HIV epidemiology in Europe by combining existing surveillance data to mathematical modelling to achieve observations closer to the dynamic reality of HIV infections across different parts of Europe. In the European Union (EU), where it is estimated that 30% of HIV-infected persons have not been diagnosed, the number of new HIV diagnoses has risen in recent years. However, trends must be interpreted with some caution around the differences and variations in surveillance systems and testing rates among affected populations and regions. By introducing mathematical models, we can build an overall picture from the pieces of information available. We present a mathematical model of the course of infection and the effect of ART which has been developed to fit as closely as possible to observed data from HIV cohorts. The preliminary estimates for the entire WHO European Region are that around 2.3 million people were living with HIV in Europe at the end of 2006, of whom around 50% have not been diagnosed. The model can also be used to assess the potential impact of earlier diagnoses. Observations show how a combination of surveillance data and modelling allows an estimation of the current state of the epidemic in Europe, though further developments in both areas are needed.


Subject(s)
Anti-Retroviral Agents/therapeutic use , HIV Infections/diagnosis , HIV-1/drug effects , Europe/epidemiology , European Union , Female , HIV Infections/epidemiology , HIV Infections/transmission , HIV Seropositivity/epidemiology , HIV Seropositivity/transmission , Humans , Male , Mandatory Testing/trends , Population Surveillance , Risk Factors
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