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Background Expanding statin use may help to alleviate the excess burden of atherosclerotic cardiovascular disease in people living with HIV (PLHIV). Pravastatin and pitavastatin are preferred agents due to their lack of substantial interaction with antiretroviral therapy. We aimed to evaluate the cost‐effectiveness of pravastatin and pitavastatin for the primary prevention of atherosclerotic cardiovascular disease among PLHIV in the United States. Methods We developed a microsimulation model that randomly selected (with replacement) individuals from the Data‐collection on Adverse Effects of Anti‐HIV Drugs study with follow‐up between 2013 and 2016. Our study population was PLHIV aged 40 to 75 years, stable on antiretroviral therapy, and not currently using lipid‐lowering therapy. Direct medical costs and quality‐adjusted life‐years (QALYs) were assigned in annual cycles and discounted at 3% per year. We assumed a willingness‐to‐pay threshold of $100,000/QALY gained. The interventions assessed were as follows: (1) treating no one with statins; (2) treating everyone with generic pravastatin 40 mg/day (drug cost $236/year) and (3) treating everyone with branded pitavastatin 4 mg/day (drug cost $2,828/year). The model simulated each individual’s probability of experiencing atherosclerotic cardiovascular disease over 20 years. Results Persons receiving pravastatin accrued 0.024 additional QALYs compared with those not receiving a statin, at an incremental cost of $1338, giving an incremental cost‐effectiveness ratio of $56,000/QALY gained. Individuals receiving pitavastatin accumulated 0.013 additional QALYs compared with those using pravastatin, at an additional cost of $18,251, giving an incremental cost‐effectiveness ratio of $1,444,000/QALY gained. These findings were most sensitive to the pill burden associated with daily statin administration, statin costs, statin efficacy and baseline atherosclerotic cardiovascular disease risk. In probabilistic sensitivity analysis, no statin was optimal in 5.2% of simulations, pravastatin was optimal in 94.8% of simulations and pitavastatin was never optimal. Conclusions Pravastatin was projected to be cost‐effective compared with no statin. With substantial price reduction, pitavastatin may be cost‐effective compared with pravastatin. These findings bode well for the expanded use of statins among PLHIV in the United States. To gain greater confidence in our conclusions it is important to generate strong, HIV‐specific estimates on the efficacy of statins and the quality‐of‐life burden associated with taking an additional daily pill.

Introduction People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (CVD) compared to their HIV‐negative peers. Expanding statin use may help alleviate this burden. However, the choice of statin in the context of antiretroviral therapy is challenging. Pravastatin and pitavastatin improve cholesterol levels in PLHIV without interacting substantially with antiretroviral therapy. They are also more expensive than most statins. We evaluated the cost‐effectiveness of pravastatin and pitavastatin for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid‐lowering therapy. Methods We developed a discrete‐state microsimulation model that randomly selected (with replacement) individuals from the TREAT Asia HIV Observational Database cohort who were aged 40 to 75 years, receiving antiretroviral therapy in Thailand, and not using lipid‐lowering therapy. The model simulated each individual’s probability of experiencing CVD. We evaluated: (1) treating no one with statins; (2) treating everyone with pravastatin 20mg/day (drug cost 7568 Thai Baht ($US243)/year) and (3) treating everyone with pitavastatin 2 mg/day (drug cost 8182 Baht ($US263)/year). Direct medical costs and quality‐adjusted life‐years (QALYs) were assigned in annual cycles over a 20‐year time horizon and discounted at 3% per year. We assumed the Thai healthcare sector perspective. Results Pravastatin was estimated to be less effective and less cost‐effective than pitavastatin and was therefore dominated (extended) by pitavastatin. Patients receiving pitavastatin accumulated 0.042 additional QALYs compared with those not using a statin, at an extra cost of 96,442 Baht ($US3095), giving an incremental cost‐effectiveness ratio of 2,300,000 Baht ($US73,812)/QALY gained. These findings were sensitive to statin costs and statin efficacy, pill burden, and targeting of PLHIV based on CVD risk. At a willingness‐to‐pay threshold of 160,000 Baht ($US5135)/QALY gained, we estimated that pravastatin would become cost‐effective at an annual cost of 415 Baht ($US13.30)/year and pitavastatin would become cost‐effective at an annual cost of 600 Baht ($US19.30)/year. Conclusions Neither pravastatin nor pitavastatin were projected to be cost‐effective for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid‐lowering therapy. We do not recommend expanding current use of these drugs among PLHIV in Thailand without substantial price reduction.

Introduction Uptake of early infant HIV diagnosis (EID) varies widely across sub-Saharan African settings. We evaluated the potential clinical impact and cost-effectiveness of universal maternal HIV screening at infant immunization visits, with referral to EID and maternal antiretroviral therapy (ART) initiation. Methods Using the CEPAC-Pediatric model, we compared two strategies for infants born in 2017 in Cote d'Ivoire (CI), South Africa (SA), and Zimbabwe: (1) existing EID programmes offering six-week nucleic acid testing (NAT) for infants with known HIV exposure (EID), and (2) EID plus universal maternal HIV screening at six-week infant immunization visits, leading to referral for infant NAT and maternal ART initiation (screen-and-test). Model inputs included published Ivoirian/South African/Zimbabwean data: maternal HIV prevalence (4.8/30.8/16.1%), current uptake of EID (40/95/65%) and six-week immunization attendance (99/74/94%). Referral rates for infant NAT and maternal ART initiation after screen-and-test were 80%. Costs included NAT ($24/infant), maternal screening ($10/mother-infant pair), ART ($5 to 31/month) and HIV care ($15 to 190/month). Model outcomes included mother-to-child transmission of HIV (MTCT) among HIV-exposed infants, and life expectancy (LE) and mean lifetime per-person costs for children with HIV (CWH) and all children born in 2017. We calculated incremental cost-effectiveness ratios (ICERs) using discounted (3%/year) lifetime costs and LE for all children. We considered two cost-effectiveness thresholds in each country: (1) the per-capita GDP ($1720/6380/2150) per year-of-life saved (YLS), and (2) the CEPAC-generated ICER of offering 2 versus 1 lifetime ART regimens (e.g. offering second-line ART; $520/500/580/YLS). Results With EID, projected six-week MTCT was 9.3% (CI), 4.2% (SA) and 5.2% (Zimbabwe). Screen-and-test decreased total MTCT by 0.2% to 0.5%, improved LE by 2.0 to 3.5 years for CWH and 0.03 to 0.07 years for all children, and increased discounted costs by $17 to 22/child (all children). The ICER of screen-and-test compared to EID was $1340/YLS (CI), $650/YLS (SA) and $670/YLS (Zimbabwe), below the per-capita GDP but above the ICER of 2 versus 1 lifetime ART regimens in all countries. Conclusions Universal maternal HIV screening at immunization visits with referral to EID and maternal ART initiation may reduce MTCT, improve paediatric LE, and be of comparable value to current HIV-related interventions in high maternal HIV prevalence settings like SA and Zimbabwe.

Introduction The unexpected identification of a neural tube defect (NTD) safety signal with preconception dolutegravir (DTG) exposure in the Botswana Tsepamo birth outcomes study brought into sharp focus the need for reliable data on use of new antiretrovirals in pregnancy, improved pharmacovigilance systems to evaluate safety of new drugs being introduced into populations including women of reproductive potential, and balanced risk‐benefit messaging when a safety signal is identified. Discussion The Tsepamo study NTD safety signal and accompanying regulatory responses led to uncertainty about the most appropriate approach to DTG use among women of reproductive potential, affecting global DTG roll‐out plans, and limiting DTG use in adolescent girls and women. It also revealed a tension between a public health approach to antiretroviral treatment (ART) and individual choice, and highlighted difficulties interpreting and messaging an unexpected safety signal with uncertainty about risk. This difficulty was compounded by the lack of high‐quality data on pregnancy outcomes from women receiving ART outside the Tsepamo surveillance sites and countries other than Botswana, resulting in a prolonged period of uncertainty while data on additional exposures are evaluated to refute or confirm the initial safety signal. We discuss principles for evaluating and introducing new drugs in the general population that would ensure collection of appropriate data to inform drug safety in adolescent girls and women of reproductive potential and minimize confusion about drug use in this population when a safety signal is identified. Conclusions The response to a signal suggesting a possible safety risk for a drug used in pregnancy or among women who may become pregnant needs to be rapid and comprehensive. It requires the existence of appropriately designed surveillance systems with broad population coverage; data analyses that examine risk‐benefit trade‐offs in a variety of contexts; guidance to transform this risk‐benefit balance into effective and agreed‐upon policy; involvement of the affected community and other key stakeholders; and a communication plan for all levels of knowledge and complexity. Implementation of this proposed framework for responding to safety signals is needed to ensure that any drug used in pregnancy can be rapidly and appropriately evaluated should a serious safety alert arise.

INTRODUCTION: Suboptimal ART adherence, despite HIV viral suppression, has been associated with chronic residual inflammation. Whether this association extends to individuals who initiate ART during early HIV infection remains unknown, which was the objective of this study.METHODS: Plasma levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein, serum amyloid A protein (SAA), IL-27, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, D-dimer and the CD4+/CD8+ T-cell ratio, were analysed at baseline and eight months after ART initiation in treatment-naïve participants with HIV and CD4+ T-cells >500 cells/mm3 enrolled in the immediate arm of START. Adherence was assessed by seven-day self-report. Multivariable linear regression was utilized to analyse the association between ART adherence and each biomarker at the eight-month visit in participants who achieved virologic suppression (RESULTS: We evaluated 1627 participants (422 female) who achieved virologic suppression at the eight-month visit in the period between 2009 and 2013. Median (IQR) CD4+ T-cell count before ART was 651 (585, 769) cells/mm3 . Incomplete adherence was reported in 109 (7%) participants at the eight month visit. After adjusting for covariates, plasma IL-6 was 1.12 (95% CI, 1.00 to 1.26; p = 0.047) fold higher in participants reporting incomplete versus 100% adherence. A similar association for SAA was observed in an exploratory analysis (1.29 (95% CI 1.04 to 1.60); p = 0.02). No significant differences in other biomarkers were observed.CONCLUSIONS: Incomplete ART adherence was associated with higher IL-6 levels in individuals who achieved virologic suppression early after ART initiation in START. A potential similar association for SAA requires confirmation. These findings suggest a role for identifying strategies to maximize ART adherence even during virologic suppression. ClinicalTrials.gov number: NCT00867048.

Introduction : For people living with HIV, the first antiretroviral treatment (ART) regimen offers the best chance for a good virological response. Early identification of those unlikely to respond to first-line ART could enable timely intervention and increase chances of a good initial treatment response. In this study we assess the extent to which the HIV RNA viral load (VL) at 1 and 3 months is predictive of first-line treatment outcome at 6 months. Methods : All previously ART-naive individuals starting ART at two London centres since 2000 with baseline (−180 to 3 days) VL >500 c/mL had a VL measurement between 6 and 12 months after starting ART, and at least one at month 1 (4–60 days) or month 3 (61–120 days) were included. Lack of treatment response was defined as (i) VL >200 copies/mL at 6 months or (ii) VL >200 copies/mL at 6 months or simultaneous switch in drugs from at least two different drug classes before 6 months. The association with VL measurements at 1 and 3 months post-ART; change from pre-ART in these values; and CD4 count measurements at 1 and 3 months were assessed using logistic regression models. The relative fit of the models was compared using the Akaike information criterion (AIC). Results : A total of 198 out of 3258 individuals (6%) experienced lack of treatment response at 6 months (definition i), increasing to 511 (16%) for definition (ii). Those with a 1-month (day 4–60 window) VL of 100,000 copies/ml had a 4%, 8%, 23% and 24% chance, respectively, of subsequently experiencing treatment non-response at 6 months (definition (i)). When considering the 3-month (day 61–120 window) VL, the chances of subsequently experiencing treatment non-response were, respectively, 3%, 25%, 67% and 75%. Results were similar for definition (ii). Conclusions : Whilst 3-month VL provides good discrimination between low and high risk of treatment failure, 1-month VL does not. Presence of a VL >10,000 copies/ml after 3 months of ART is a cutoff above which individuals are at a sufficiently higher risk of non-response that they may be considered for intervention. Keywords initial virological response; HIV; ART; response to ART; HIV treatment; VL response to ART (Published: 30 August 2017) Brima N et al. Journal of the International AIDS Society 2017, 20 :21567 http://www.jiasociety.org/index.php/jias/article/view/21567 | http://dx.doi.org/10.7448/IAS.20.1.21567

Introduction The 90‐90‐90 targets set by the United Nations aspire to 73% of people living with HIV (PLHIV) being virally suppressed by 2020. Using the HIV Synthesis Model, we aim to mimic the epidemic in Zimbabwe and make projections to assess whether Zimbabwe is on track to meet the 90‐90‐90 targets and assess whether recently proposed UNAIDS HIV transition metrics are likely to be met. Methods We used an approximate Bayesian computation approach to identify model parameter values which result in model outputs consistent with observed data, evaluated using a calibration score. These parameter values were then used to make projections to 2020 to compare with the 90‐90‐90 targets and other key indicators. We also calculated HIV transition metrics proposed by UNAIDS (percentage reduction in new HIV infections and AIDS‐related mortality from 2010 to 2020, absolute rate of new infections and AIDS‐related mortality, incidence–mortality ratio and incidence–prevalence ratios). Results After calibration, there was general agreement between modelled and observed data. The median predicted outcomes in 2020 were: proportion of PLHIV (aged 15 to 65) diagnosed 0.91 (90% uncertainty range 0.87, 0.94) (0.84 men, 0.95 women); of those diagnosed, proportion on treatment 0.92 (0.90, 0.93); of those receiving treatment, proportion with viral suppression 0.86 (0.81, 0.91). This results in 72% of PLHIV having viral suppression in 2020. We estimated a percentage reduction of 36.5% (13.7% increase to 67.4% reduction) in new infections from 2010 to 2020, and of 30.4% (9.7% increase to 56.6% reduction) in AIDS‐related mortality (UNAIDS target 75%). The modelled absolute rates of HIV incidence and AIDS‐related mortality in 2020 were 5.48 (2.26, 9.24) and 1.93 (1.31, 2.71) per 1000 person‐years respectively. The modelled incidence–mortality ratio and incidence–prevalence ratios in 2020 were 1.05 (0.46, 1.66) and 0.009 (0.004, 0.013) respectively. Conclusions Our model was able to produce outputs that are simultaneously consistent with an array of observed data and predicted that while the 90‐90‐90 targets are within reach in Zimbabwe, increased efforts are required in diagnosing men in particular. Calculation of the HIV transition metrics suggest increased efforts are needed to bring the HIV epidemic under control.

Introduction : In the United Kingdom, rates of virological suppression on antiretroviral therapy (ART) are very high, but there remain a small but significant number of people on ART with detectable viraemia. The impact of socio-economic factors on virological suppression has been little studied. Materials and Methods : We used data from ASTRA, a cross-sectional, questionnaire study of >3000 individuals from 8 clinics in the United Kingdom in 2011–2012, linked to clinical records to address this question. Included participants had received ART for >6 months with a recorded current viral load (VL) (latest at the time of questionnaire). Participants provided data on demographic factors: gender, sexual orientation, ethnicity and age; and socio-economic factors: UK birth/English reading ability, employment, housing, education and financial hardship. To assess non-adherence, participants were asked if in the past 3 months, they had missed ART for ≥2 days at a time. Virological suppression was defined as VL≤50 cps/mL. For each socio-economic factor, we calculated prevalence ratios using modified Poisson regression, first adjusting for demographic factors, then also for non-adherence. Results : A total of 2445 people fulfilled the inclusion criteria (80% male, 69% MSM, median age: 46 years, median CD4 count: 556 cells/mm 3 ); 10% (234/2445) had VL>50 cps/mL. After adjusting for demographic factors, non-fluent English, not being employed, not home owning, education below university level and increasing financial hardship were each associated with higher prevalence of VL>50 cps/mL. Additional adjustment for non-adherence largely attenuated each association, but did not fully explain them (see Table 1). After adjustment for non-adherence and demographic factors, younger age was also associated with VL>50 cps/mL: for each additional 10 years an individual was 0.80 (95% CI 0.70–0.92) times as likely to have VL>50 cps/mL (p=0.0019). Adjusted prevalence ratios for VL>50cps/mL were 0.91 (0.62–1.34) for women and 1.25 (0.85–1.84) for non-MSM men versus MSM, and 1.29 (0.92–1.80) for white versus non-white people. Conclusions : Among people on ART in the United Kingdom, the proportion with detectable VL is low. Poorer socio-economic status is associated with increased probability of virological non-suppression. It is likely that much of this association is mediated through difficulties in taking ART. Emphasis should be put on aiding the adherence of people in these higher risk groups. (Published: 2 November 2014) Citation : Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Burch L et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19533 http://www.jiasociety.org/index.php/jias/article/view/19533 | http://dx.doi.org/10.7448/IAS.17.4.19533

Introduction : Most people achieve and maintain viral load (VL) suppression on first-line antiretroviral therapy (ART) but for a minority this does not happen. It is unclear whether those who have maintained VL suppression for several years will be able to continue to do so, or if rates of VL failure – due to poor adherence, ART interruption and/or resistance – remain at appreciable levels. Methods : Eligible participants were ART-naive and started treatment after 1st January 2000, with ≥3 antiretrovirals and ≥9 months follow-up. VL failure was defined as failure to achieve VL suppression (≤50 copies/mL) by 9 months on ART or a single VL >200 copies/mL after 9 months after start of ART. Kaplan-Meier estimates were used to examine the cumulative probability of experiencing a VL >200 copies/mL over time, irrespective of treatment interruption (Figure 1). Follow-up was censored at last VL assessment but not at treatment interruption. In a sensitivity analysis, VL failure was instead defined as two consecutive VL >1000 copies/mL. Results : A total of 13,556 participants were included. Median (IQR) age at start of ART was 37 (32–43), median follow-up 4.1 (2.3–6.7) years, pre-ART VL 71,400 (17,400–221,900) copies/mL and pre-ART CD4 count 204 (110–290) cells/mm 3 . Fifty-one percent were white, 71% male and 50% MSM. Of which, 5,351 (39%) participants experienced a VL >200 copies/mL. In sub-groups of participants the proportion experiencing a VL >200 copies/mL by one year after start of ART were: 200 copies/ml was 8 years. In sensitivity analyses based on 12,811 participants, 4274 (33%) experienced two consecutive VL >1000 copies/mL. Table 1 presents the rate of experiencing a VL >200 copies/mL (two consecutive VL >1000 copies/mL) by time since start of ART. The rate of VL >200 copies/mL declines over time, from 30 per 100 person-years after up to two years after ART, to two per 100 person-years after up to 11.5 years after ART. A sum of 2,047 (15%) participants stopped ART at some point (10, 14 and 17% had stopped ART by 1, 3, and 5 years, respectively). Conclusions : Although resistance will often not be present and, even if present, several drug options will likely remain, first occurrence of VL > 200 copies/mL after having attained viral suppression continues to occur after 10 years on ART. (Published: 2 November 2014) Citation : Abstracts of the HIV Drug Therapy Glasgow Congress 2014 O’Connor J et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19527 http://www.jiasociety.org/index.php/jias/article/view/19527 | http://dx.doi.org/10.7448/IAS.17.4.19527

Introduction : Transmission of Hepatitis C virus (HCV) among HIV-positive men who have sex with men (MSM) in the United Kingdom is ongoing. We explore associations between self-reported sexual behaviours and drug use with cumulative HCV prevalence, as well as new HCV diagnosis. Methods : ASTRA is a cross-sectional questionnaire study including 2,248 HIV-diagnosed MSM under care in the United Kingdom during 2011–2012. Socio-demographic, lifestyle, HIV-related and sexual behaviour data were collected during the study. One thousand seven hundred and fifty two (≥70%) of the MSM who consented to linkage of ASTRA and clinical information (prior to and post questionnaire) were included. Cumulative prevalence of HCV was defined as any positive anti-HCV or HCV-RNA test result at any point prior to questionnaire completion. We excluded 536 participants with clinical records only after questionnaire completion. Among the remaining 1,216 MSM, we describe associations of self-reported sexual behaviours and recreational drug use in the three months prior to ASTRA with cumulative HCV prevalence, using modified Poisson regression with robust error variances. New HCV was defined as any positive anti-HCV or HCV-RNA after questionnaire completion. We excluded 591 MSM who reported ever having a HCV diagnosis at questionnaire, any positive HCV result prior to questionnaire or did not have any HCV tests after the questionnaire. Among the remaining 1,195 MSM, we describe occurrence of new HCV diagnosis during follow-up according to self-reported sexual behaviours and recreational drug use three months prior to questionnaire (Fisher's exact test). Results : Cumulative HCV prevalence among MSM prior to ASTRA was 13.3% (95% CI 11.5–15.4). Clinic- and age-adjusted prevalence ratios (95% CI) for cumulative HCV prevalence were 4.6 (3.1–6.7) for methamphetamine, 6.5 (3.5–12.1) for injection drugs, 2.3 (1.6–3.4) for gamma hydroxybutyrate (GHB), 1.6 (1.3–2.0) for nitrites, 1.7 (1.5–2.0) for all condom-less sex (CLS), 2.1 (1.7–2.5) for CLS-HIV-seroconcordant, 1.3 (0.9–1.9) for CLS-HIV-serodiscordant, 2.0 (1.6–2.5) for group sex, 1.5 (1.2–1.9) for more than 10 new sexual partners in the past year. Among 1,195 MSM with 2.2 years [IQR 1.5–2.4] median follow-up, there were 7 new HCV cases during 2,033 person-years at risk. Incidence was 3.5 per 1,000 person-years (95% CI 1.6–7.2). New HCV was recorded in 1.3% MSM who used methamphetamine versus 0.5% MSM who did not (p=0.385); 3.7% MSM who injected recreational drugs versus 0.5% MSM who did not (p=0.148); 2.9% MSM who used GHB versus 0.4% MSM who did not (p=0.003); 1.5% MSM who used nitrites versus 0.2% MSM who did not (p=0.019); 1.1% MSM having CLS versus 0.3% MSM who did not (p=0.084); 1.7% MSM having CLS-HIV-serodiscordant versus 0.4% MSM who did not (p=0.069); 0.9% MSM who had CLS-HIV-seroconcordant versus 0.5% MSM who did not (p=0.318); 0.8% MSM who had group sex versus 0.5% MSM who did not (p=0.463); and 1.6% MSM with =10 new sexual partners in the previous year versus 0.2% MSM with no or up to 9 new partners (p=0.015). Conclusions : Self-reported recent use of recreational and injection drugs, condom-less sex and multiple new sexual partners are associated with pre-existing HCV infection and, with the exception of injection drugs, appear to be predictive of new HCV co-infection among HIV-diagnosed MSM. (Published: 2 November 2014) Citation : Daskalopoulou M et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19630 http://www.jiasociety.org/index.php/jias/article/view/19630 | http://dx.doi.org/10.7448/IAS.17.4.19630

Introduction: Several resistance mutations have been shown to affect viral fitness, and the presence of certain mutations might result in clinical benefit for patients kept on a virologically failing regimen due to an exhaustion of drug options. We sought to quantify the effect of resistance mutations on CD4 slopes in patients undergoing episodes of viral failure. Materials and Methods: Patients from the EuroSIDA and UK CHIC cohorts undergoing at least one episode of virological failure (>3 consecutive RNA measurements >500 on ART) with at least three CD4 measurements and a resistance test during the episode were included. Mutations were identified using the IAS-US (2013) list, and were presumed to be present from detection until the end of an episode. Multivariable linear mixed models with a random intercept and slope adjusted for age, baseline CD4 count, hepatitis C, drug type, RNA (log-scale), risk group and subtype were used to estimate CD4 slopes. Individual mutations with a population prevalence of >10% were tested for their effect on the CD4 slope. Results: A total of 2731 patients experiencing a median of 1 (range 1–4) episodes were included in this analysis. The prevalence of any resistance per episode was 88.4%; NNRTI resistance was most common (78.5%). Overall, CD4 counts declined by 17.1 (−19.7; −14.5) cells per year; this decline was less marked with partial viral suppression (current HIV RNA more than 1.5 log below the setpoint; p=0.01). In multivariable models adjusting for viral load, CD4 decline was slower during episodes with detected resistance compared to episodes without detected resistance (21.0 cells/year less, 95% CI 11.75–30.31, p

Introduction: Darunavir (DRV) is a preferred agent in treatment guidelines for ART-naive and experienced patients [1]. It is considered to have a high genetic barrier to resistance and 11 resistance-associated mutations (RAMs) are recognized by IAS-USA [2]. These have largely been identified by analyses examining the correlation between baseline genotype and virological response [3]. However, there is little information on RAMs that are directly selected by DRV, outside of short-term clinical trials. We aimed to identify emerging mutations by comparing the genotypes of individuals before and after DRV exposure. Materials and Methods: The UK HIV Drug Resistance Database was used to identify patients aged over 16 who had received at least 30 days of a DRV-containing regimen. Patients were included if they had a “baseline” resistance test, prior to DRV exposure, and a “repeat” test, either on DRV or within 30 days of stopping this agent. To avoid attributing the effects of other PIs on emerging RAMs to DRV, patients were excluded if they had received another PI for greater than 90 days between the baseline genotype and the start of DRV. The baseline and repeat tests were compared to determine the nature of mutations stratified by PI history. Results: A total of 5623 patients had DRV, of whom 306 met the inclusion criteria. A total of 228 (74.5%) were male, median age at the start of DRV was 42 years (IQR 37–47), and half had subtype B infection. The mode of transmission was homosexual contact for 50%, heterosexual for 38%, and 3% were injection drug users. The median CD4 count at the start of DRV was 257 cells/mm 3 (IQR 94–453). A total of 149 patients (49%) had a history of PI use prior to DRV, and 157 (51%) were PI-naive. The most common previous PIs were lopinavir, atazanavir, and saquinavir. Baseline DRV RAMs were present in 1 (0.6%) PI-naive and 20 (13.4%) PI-experienced patients. Mutations emerged under DRV pressure in a further 3 (1.9%) PI-naive patients, and in 7 (4.7%) PI-experienced patients, 5 of whom had other DRV RAMs present at baseline (Table 1). The median time from the start of DRV to the repeat test was 196 days for PI-naive patients and 296 days for PI-experienced. Conclusions: PI-experienced patients had a greater prevalence of DRV RAMs at baseline than PI-naive individuals, probably due to the fact that some DRV RAMs can be selected by other PIs. This group also accumulated more RAMs during DRV exposure, possibly because previous PIs had caused minority variants which then emerged on DRV therapy. Overall, only 10 patients accumulated 16 RAMs, which supports the perception that DRV has a high genetic barrier to resistance. Repeat genotyping in the case of virological failure on DRV may still be warranted to detect emerging resistance and guide management decisions. (Published: 2 November 2014) Citation: Abstracts of the HIV Drug Therapy Glasgow Congress 2014 El Bouzidi K et al. Journal of the International AIDS Society 2014, 17(Suppl 3): 19739 http://www.jiasociety.org/index.php/jias/article/view/19739 | http://dx.doi.org/10.7448/IAS.17.4.19739