Risk Of Virological Failure Research Articles

Viral suppression in adults, adolescents and children receiving antiretroviral therapy in Cameroon: adolescents at high risk of virological failure in the era of \u201ctest and treat\u201d

BackgroundAfter the launching of the « Test & Treat » strategy and the wider accessibility to viral load (VL), evaluating virological success (VS) would help in meeting the UNAIDS targets by 2020 in Cameroon.Setting and methodsCross-sectional study conducted in the Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management (CIRCB), Yaoundé, Cameroon; data generated between October 2016 and August 2017 amongst adults, adolescents and children at 12, 24, 36 and ≥ 48 months on ART. VS was defined as < 1000 copies/mL of blood plasma and controlled viremia as VL < 50 copies/mL. Data were analysed by SPSS; p < 0.05 considered as significant.Results1946 patients (70% female) were enrolled (1800 adults, 105 adolescents, 41 children); 1841 were on NNRTI-based and 105 on PI-based therapy; with 346 patients at M12, 270 at M24, 205 at M36 and 1125 at ≥ M48. The median (IQR) duration on was 48 months (24–48). Overall, VS was 79.4% (95% CI 77.6–81.2) and 67.1% (95% CI 64.9–69.1) had controlled viral replication. On NNRTI-based, VS was 79.9% vs. 71.4% on PIs-based, p = 0.003. By ART duration, VS was 84.1% (M12), 85.9% (M24), 75.1% (M36) and 77.2% (≥ M48), p = 0.001. By age, VS was 75.6% (children), 53.3% (adolescents) and 81.1% (adults), p < 0.001.ConclusionsIn this sub-population of patients receiving ART in Cameroon, about 80% might be experiencing VS, with declining performance at adolescence, with NNRTI-based regimens, and as from 36 months on ART. Thus, improving VS may require an adapted adherence support mechanism, especially for adolescents with long-term treatment in resource-limited settings.

The Impact of Cumulative Depression Along the HIV Care Continuum in Women Living With HIV During the Era of Universal Antiretroviral Treatment.

Data are limited on cumulative impacts of depression on engagement in care and HIV outcomes in women living with HIV (WLWH) during the era of universal antiretroviral therapy (ART). Understanding the relationship of accumulated depression with HIV disease management may help identify benefits of interventions to reduce severity and duration of depressive episodes. A cohort of WLWH (N = 1491) from the Women's Interagency HIV Study at 9 sites across the US. This longitudinal observational cohort study (2013-2017) followed WLWH for a maximum of 9 semiannual visits. Depression was quantified as a time-updated measure of percent of days depressed (PDD) created from repeated assessments using the Center for Epidemiologic Studies Depression scale. Marginal structural Poisson regression models were used to estimate the effects of PDD on the risks of missing an HIV care appointment, <95% ART adherence, and virological failure (≥200 copies/mL). The risk of missing an HIV care appointment [risk ratio (RR) = 1.16, 95% confidence interval = 0.93 to 1.45; risk difference (RD) = 0.01, -0.01 to 0.03], being <95% ART adherent (RR = 1.27, 1.06-1.52; RD = 0.04, -0.01 to 0.07), and virological failure (RR = 1.09, 1.01-1.18; RD = 0.01, -0.01 to 0.03) increased monotonically with increasing PDD (comparing those with 25 to those with 0 PDD). The total effect of PDD on virological failure was fully (%100) mediated by being <95% ART adherent. Time spent depressed increases the risk of virological failure through ART adherence, even in the era of universal ART regimes forgiving of imperfect adherence.

301. Risk of Virologic Failure with Antiretroviral Switches in HIV/HCV Co-infections

BackgroundDirect-acting antivirals (DAA) and antiretroviral (ARV) medications pose treatment challenges in HIV/HCV co-infection. Management of contraindicated combinations varies across practices. ARV switches may increase the risk of HIV virologic and treatment failure, and has been reported to increase the risk of DAA treatment failure. This analysis assesses how switches in ARV regimen impacts treatment outcomes in HIV/HCV co-infection.MethodsThis retrospective cohort study includes patients 18 years and older with stable HIV/HCV co-infection (HIV RNA<50 for ≥6 months) who received DAA HCV therapy. Data were obtained using the Centers for AIDS Research Network of Integrated Clinical Systems. The “ARV switch” cohort is defined as patients undergoing a switch in ARV regimen within 6 months prior to DAA treatment. The “no ARV switch” cohort was defined as patients without a change in ARV during the same time period. The primary outcome is HIV treatment failure which is a composite endpoint including HIV virologic failure (defined as confirmed loss of HIV viral suppression), discontinuation/change of ARV regimen, progression to AIDS, or death. We compared baseline characteristics, the proportion of patients free of HIV treatment failure, free of HIV virologic failure, and that achieved sustained viral response (SVR) at 12 and 24 weeks after DAA treatment among ARV switch and no ARV switch groups.ResultsOf the 256 patients, 63/256 (25%) underwent an ARV switch (Table 1). At baseline, the most common regimen in the ARV switch group was protease inhibitor (PI)-based while for the no ARV switch group, it was an integrase strand transfer inhibitor (INSTI)-based regimen. HIV/HCV transmission risk factors, HCV genotype, and AST/ALT were similar among the two groups (Table 1). The proportion with HIV treatment and virologic failure, and the proportion achieving SVR12/24 were similar among the ARV switch and no ARV switch groups.ConclusionHIV treatment and virologic failure, and SVR12/24 were not different among patients who did or did not undergo a switch in their ARV regimen prior to DAA treatment. This suggests that switches in the ARV regimen for DAA treatment of HCV do not negatively impact HIV or HCV outcomes among patients with HIV/HCV Coinfection. Disclosures All authors: No reported disclosures.

No impact of previous NRTIs resistance in HIV positive patients switched to DTG+2NRTIs under virological control: Time of viral suppression makes the difference.

The accumulation of drug-resistance mutations on combined antiretroviral regimens (ART) backbone could affect the virological efficacy of the regimen. Our aim was to assess the impact of previous drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) on the probability of virological failure (VF) in patients, under virological control, who switched to dolutegravir (DTG)+2NRTIs regimens. All HIV-1 positive drug-experienced patients who started a regimen composed by DTG+2NRTIs [abacavir/lamivudine or tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF)/emtricitabine (FTC)] in the ARCA collaborative group with HIV-RNA <50 cp/mL were included in the analysis. Patients with a previous VF to integrase inhibitors were excluded. The impact of single and combined NRTIs mutations on the probability of VF (defined as 2 consecutive HIV-RNA >50 copies/mL or one HIV-RNA >1000 copies/mL) was assessed by Kaplan Meier curves. A multivariable Cox regression analysis was constructed to assess factors potentially related to VF. Five hundred and eighty-eight patients were included in the analysis with a median time of viral suppression before the switch of 37 months (IQR 12–78), of whom 148 (25.2%) had at least one previous NRTIs resistance mutation. In the multivariable model no association was observed between NRTIs mutations and VF. Conversely, the duration of viral suppression before switch resulted associated with a lower risk of VF (for 1 month increase, adjusted Hazard Ratio 0.98, 95%CI 0.96–0.99; p=0.024). Previous NRTIs mutations appeared to have no impact on the risk of VF in patients switched to DTG+2NRTIs, whereas a longer interval on a controlled viremia decreased significantly the risk of VF.

Associations between baseline characteristics, CD4 cell count response and virological failure on first-line efavirenz + tenofovir + emtricitabine for HIV

ObjectivesThe aim of this study was to investigate associations between baseline characteristics and CD4 cell count response on first-line antiretroviral therapy and risk of virological failure (VF) with or without drug resistance. MethodsWe conducted an analysis of UK Collaborative HIV Cohort data linked to the UK HIV Drug Resistance Database. Inclusion criteria were viral sequence showing no resistance prior to initiation of first-line efavirenz + tenofovir disoproxil fumarate + emtricitabine and virological suppression within 6 months. Outcomes of VF (≥200 copies/mL) with or without drug resistance were assessed using a competing risks approach fitted jointly with a model for CD4 cell count recovery. Hazard ratios for each VF outcome were estimated for baseline CD4 cell count and viral load and characteristics of CD4 cell count response using latent variables on a standard normal scale. ResultsA total of 3640 people were included with 338 VF events; corresponding viral sequences were available in 134 with ≥1 resistance mutation in 36. VF with resistance was associated with lower baseline CD4 (0.30, 0.09–0.62), lower CD4 recovery (0.04, 0.00–0.17) and higher CD4 variability (4.40, 1.22–12.68). A different pattern of associations was observed for VF without resistance, but the strength of these results was less consistent across sensitivity analyses. Cumulative incidence of VF with resistance was estimated to be >2% at 3 years for baseline CD4 ≥350 cells/μL. ConclusionLower baseline CD4 cell count and suboptimal CD4 recovery are associated with VF with drug resistance. People with low CD4 cell count before ART or with suboptimal CD4 recovery on treatment should be a priority for regimens with high genetic barrier to resistance.

Abstract # 3251 You sleep, but your heart is not in it - the importance of nocturnal autonomic signalling

Although experts have recommended testing for pretreatment drug resistance (PDR) before antiretroviral therapy (ART) initiation, there is little evidence to support its implementation. We aimed to establish whether an inexpensive point mutation assay can improve virological suppression by identifying PDR to guide drug selection for ART in a lower-middle income country.Investigators did an open-label, randomised controlled trial at three HIV treatment sites in Kenya: two in Nairobi and one in rural Maseno. Individuals (aged ≥2 years) were eligible to participate if they were confirmed HIV-seropositive, qualified for first-line ART, planned to reside in the area for more than 1 year, and provided informed consent. We randomly assigned participants (1:1) to either PDR testing by oligonucleotide ligation assay (OLA) to guide selection of ART or to standard of care, which did not include OLA testing. The OLA-guided therapy group had pre-ART peripheral blood mononuclear cells evaluated for drug resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) at codons Lys103Asn, Tyr181Cys, Gly190Ala, and to lamivudine at Met184Val, and when at least one drug-resistant codon was detected in a participant's pre-ART specimen, clinicians were directed to prescribe protease inhibitor-based second-line ART. Those without detected resistance and those who were randomised to standard of care received NNRTI-based first-line ART. The primary outcome was plasma HIV-1 RNA of at least 400 copies per mL at 4, 8, or 12 months after ART initiation, which defined virological failure, assessed in all participants who received treatment (data were censored for those lost-to-follow-up or who died). The study has been completed and is registered with ClinicalTrials.gov, NCT01898754.We screened 1198 participants between May 28, 2013, and Nov 4, 2014, of whom 991 (83%) were enrolled (492 received OLA and 495 received standard of care; four did not begin treatment). 93 participants (prevalence 9·4%) had PDR (95% CI 7·7–11·4). 34 (8·5%) of 400 participants in the OLA group had virological failure at month 12 of ART (95% CI 6·0–11·7) compared with 39 (9·7%) of 402 (7·0–13·0) in the standard-of-care group (log-rank p=0·26). Among participants with PDR, virological failure was lower in the OLA-guided therapy group than in the standard-of-care group: five (14%) of 35 compared with 13 (50%) of 26; p=0·0020). Among those prescribed NNRTI-based ART, participants given efavirenz were less likely to have virological failure than were those receiving nevirapine (odds ratio 0·37, 95% CI 0·22–0·62; p<0·0001). The OLA-guided therapy group had 39 serious non-lethal adverse events and 34 deaths. The standard-of-care group had 34 severe adverse events and 43 deaths, differences that were not significant. Adverse events judged to potentially be due to ART were few and similar between groups, with 17 (16%) in the OLA-guided therapy group and 16 (16%) in the standard-of-care group (p=0·90).Our finding that OLA testing for PDR reduced virological failure in only those with specific PDR mutations suggests that PDR poses less of a risk for virological failure than that predicted by past prevalence estimates, and that the value of PDR testing to reduce virological failure should be assessed for antiretroviral treatment regimens.US National Institutes of Health.

Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross-sectional study

ObjectivesWe assessed the prevalence and risk factors associated with virological failure among female sex workers living with HIV on antiretroviral therapy (ART) in Kampala, Uganda.MethodsWe conducted a cross-sectional study between...

Use of darunavir in HIV-1-infected individuals in routine clinical practice from 2012 to 2016 in France.

We assessed virological outcomes of darunavir use in France from 2012 to 2016, in three groups of people living with HIV (PLHIV): (i) antiretroviral (ARV)-naive PLHIV; (ii) ARV-experienced PLHIV switching to darunavir while failing therapy; and (iii) ARV-experienced PLHIV switching to darunavir while virologically controlled. Virological success (VS) was defined as a plasma HIV-1 viral load (VL) <50 copies/mL and virological failure (VF) as two consecutive VL >50 copies/mL or one VL >50 copies/mL followed by a treatment switch prior to the next VL measurement. The cumulative incidence of VS was assessed considering darunavir discontinuation, loss to follow-up and death as competing risks, while estimates of cumulative incidence of VF accounted for loss to follow-up and death. Among the 3235 ARV-naive PLHIV initiating darunavir, the 4 year cumulative incidence of VS was 80.9% and was associated with lower VL and higher CD4 cell counts. Among the 3485 ARV-experienced PLHIV switching to darunavir while failing therapy, the 4 year cumulative incidence of VS was 82.2% and was associated with lower VL. Among the 3005 ARV-experienced PLHIV switching to darunavir while virologically controlled, the 4 year cumulative incidence of VF was 12.6%. The risk of VF was higher with darunavir monotherapy [subdistribution hazard ratio (sHR)=1.67, 95% CI 1.15-2.42] while no difference was observed with dual therapy (sHR = 1.00, 95% CI 0.71-1.42) relative to triple therapy or more. Darunavir-containing regimens yielded similarly high rates of viral suppression in PLHIV whether they were ARV naive or ARV experienced switching to darunavir while failing therapy, or of maintaining VS in ARV-experienced PLHIV switching to darunavir while virologically controlled.

Longitudinal virological outcomes and factors associated with virological failure in behaviorally HIV-infected young adults on combination antiretroviral treatment in the Netherlands, 2000 to 2015.

Achieving and maintaining viral suppression in young adults (18–24 years) living with HIV is challenging. Overall HIV viral suppression rates are lower in young as compared to older adults. Longitudinal data provide valuable insight on dynamics of viral suppression and variables of potential influence on HIV virological failure (VF), but is scarce in young adults living with HIV on combination antiretroviral therapy (cART). We evaluated longitudinal virological outcomes of behaviorally young adults (18–24 years) living with HIV in the Netherlands over a period of 15 years.We analyzed data from the Dutch national HIV database of 816 young adults living with HIV on cART in the Netherlands from 2000 to 2015. VF was defined as 2 consecutive detectable plasma HIV-1 viral load (VL) measurements > 200 copies/ml. Generalized linear mixed model analyses were used to assess HIV VF over time and identify risk factors associated with VF.VF during the study follow-up occurred at least once in 26% of cases. The probability of experiencing VF decreased over the study period per calendar year (OR 0.78, 95% confidence interval [CI];0.72; 0.85). Factors significantly associated with VF were being infected through heterosexual contact (OR 5.20, CI 1.39;19.38) and originating from Latin America or the Caribbean (OR 6.59, CI 2.08;20.92). Smaller, yet significant risk factors for VF were being infected through a blood transfusion or a needle accident (OR9.93, CI 1.34;73.84, and having started with cART with a nadir CD4 count >500 cells/μl (OR 11.36, CI 2.03;63.48).In our large cohort of young adults, the risk of VF has diminished over 15 years. Specific subgroups were identified to be at risk for suboptimal treatment.

Trends in medication adherence in HIV patients in the US, 2001 to 2012: an observational cohort study.

IntroductionAdherence to antiretroviral therapy (ART) is essential to reduce HIV‐related morbidity and mortality as well as the risk of virological failure and HIV transmission. We determined the trends in ART adherence during the periods of therapeutic advances, wider use of ART and greater attention to ART adherence. To understand the general trends in medication adherence, we compared ART adherence with medications for other common chronic conditions.MethodsA retrospective cohort study using Medicaid claims between 2001 and 2012 from 14 US states with the highest HIV prevalence. Medicaid is the largest source of care for HIV patients in the US. We identified Medicaid beneficiaries with HIV who initiated ART between 2001 and 2010 (n=23,343). Comparison groups included (1) HIV‐ persons who initiated a statin, angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB), or metformin and (2) HIV+ persons who initiated these control medications while on and not on ART. We estimated adjusted odds of >90% medication implementation during the two years following initiation.ResultsThe proportion of HIV+ persons with >90% ART implementation increased from 33.5% in those who initiated in 2001 to 46.4% in 2005 and 52.4% in 2010. ART initiators in 2007 to 2010 had 53% increased odds of >90% implementation compared to those in 2001 to 2003 (adjusted OR 1.53, 99% CI: 1.34 to 1.75). Older age, male, White race, newer ART regimens and absence of substance use indicators were also associated with increased odds of >90% ART implementation. No or minimal improvements were found in the implementation of control medications in HIV‐ persons. For HIV‐ persons, the adjusted ORs comparing 2007–2010 to 2001–2003 were 1.06, 1.01 and 1.19 for statins, ACEI/ARB, metformin respectively. HIV+ persons who were on ART had, on average, 15.0 (SD: 4.2) and 16.1 (SD: 3.4) percentage points higher >90% implementation rates of concurrent statins, ACEI/ARB or metformin compared to HIV‐ persons and HIV+ persons who were not on ART respectively.ConclusionsAdherence to ART substantially improved between 2001 and 2012. Nevertheless, the absolute rates of >90% implementation were low for all groups examined. Substantial disparities by age, sex and race were present, drawing attention to the need to continue to enhance medication adherence. Further studies are required to examine whether these trends and disparities persist in the most recent period.

A systematic review of the genetic mechanisms of dolutegravir resistance.

BackgroundCharacterizing the mutations selected by the integrase strand transfer inhibitor (INSTI) dolutegravir and their effects on susceptibility is essential for identifying viruses less likely to respond to dolutegravir therapy and for monitoring persons with virological failure (VF) on dolutegravir therapy.MethodsWe systematically reviewed dolutegravir resistance studies to identify mutations emerging under dolutegravir selection pressure, the effect of INSTI resistance mutations on in vitro dolutegravir susceptibility, and the virological efficacy of dolutegravir in antiretroviral-experienced persons.Results and conclusionsWe analysed 14 studies describing 84 in vitro passage experiments, 26 studies describing 63 persons developing VF plus INSTI resistance mutations on a dolutegravir-containing regimen, 41 studies describing dolutegravir susceptibility results, and 22 clinical trials and 16 cohort studies of dolutegravir-containing regimens. The most common INSTI resistance mutations in persons with VF on a dolutegravir-containing regimen were R263K, G118R, N155H and Q148H/R, with R263K and G118R predominating in previously INSTI-naive persons. R263K reduced dolutegravir susceptibility ∼2-fold. G118R generally reduced dolutegravir susceptibility >5-fold. The highest levels of reduced susceptibility occurred in viruses containing Q148 mutations in combination with G140 and/or E138 mutations. Dolutegravir two-drug regimens were highly effective for first-line therapy and for virologically suppressed persons provided dolutegravir’s companion drug was fully active. Dolutegravir three-drug regimens were highly effective for salvage therapy in INSTI-naive persons provided one or more of dolutegravir’s companion drugs was fully active. However, dolutegravir monotherapy in virologically suppressed persons and functional dolutegravir monotherapy in persons with active viral replication were associated with a non-trivial risk of VF plus INSTI resistance mutations.

Cost-Effectiveness of Preemptive Switching to Efavirenz-Based Antiretroviral Therapy for Children With Human Immunodeficiency Virus.

BackgroundThe NEVEREST-3 (South Africa) and MONOD-ANRS-12206 (Côte d’Ivoire, Burkina Faso) randomized trials found that switching to efavirenz (EFV) in human immunodeficiency virus–infected children >3 years old who were virologically suppressed by ritonavir-boosted lopinavir (LPV/r) was noninferior to continuing o LPV/r. We evaluated the cost-effectiveness of this strategy using the Cost-Effectiveness of Preventing AIDS Complications–Pediatric model.MethodsWe examined 3 strategies in South African children aged ≥3 years who were virologically suppressed by LPV/r: (1) continued LPV/r, even in case of virologic failure, without second-line regimens; continued on LPV/r with second-line option after observed virologic failure; and preemptive switch to EFV-based antiretroviral therapy (ART), with return to LPV/r after observed virologic failure. We derived data on 24-week suppression (<1000 copies/mL) after a switch to EFV (98.4%) and the subsequent risk of virologic failure (LPV/r, 0.23%/mo; EFV, 0.15%/mo) from NEVEREST-3 data; we obtained ART costs (LPV/r, $6–$20/mo; EFV, $3–$6/mo) from published sources. We projected discounted life expectancy (LE) and lifetime costs per person. A secondary analysis used data from MONOD-ANRS-12206 in Côte d’Ivoire.ResultsContinued LPV/r led to the shortest LE (18.2 years) and the highest per-person lifetime cost ($19 470). LPV/r with second-line option increased LE (19.9 years) and decreased per-person lifetime costs($16 070). Switching led to the longest LE (20.4 years) and the lowest per-person lifetime cost ($15 240); this strategy was cost saving under plausible variations in key parameters. Using MONOD-ANRS-12206 data in Côte d’Ivoire, the Switch strategy remained cost saving only compared with continued LPV/r, but the LPV/r with second-line option strategy was cost-effective compared with switching.ConclusionFor children ≥3 years old and virologically suppressed by LPV/r-based ART, preemptive switching to EFV can improve long-term clinical outcomes and be cost saving.Clinical Trials RegistrationNCT01127204

First-line antiretroviral treatment and virological response among HIV adult patients at an accredited HIV care center, Cameroon

BackgroundViral load (VL) monitoring in the clinical follow-up of HIV patients to detect treatment failure is not routinely offered in Cameroon. The study was designed to characterize virological response on antiretroviral treatment (ART) among adults living with HIV and to identify predictors of virological failure (VF).MethodsBetween November 2014 and January 2016, a prospective, population-based cohort study was conducted among HIV-positive adults under first-line treatment and monitored at the Accredited HIV Care Center (AHCC) of Laquintinie Hospital of Douala. Clinical and biological data at the initiation of ART were collected from patients’ medical records. HIV VL at 12 and 24 months after the patient started treatment on ART were performed using quantitative real-time PCR protocol with the generic HIV Roche TaqMan assay. Descriptive and logistic regression analysis were performed in Stata SE11 version in data analysis.ResultsOverall 150 (45.5%) of 330 adults living with HIV were tested with at least one VL, and of these patients, 51 (34.0%) were tested with two VL during the followed-up. The VF was observed in 13 of 51 (25.5%) patients and among them, 8 (61.5%) switched to second-line ART regimens. Thirty-five (68.6%) of the 51 patients had an undetectable VL at the first VL measurement, and seven (13.7%) patients subsequently developed viral load rebound (VLR) on tritherapy. Using a multivariate analysis, the risk of VF was seven times higher in HIV adults who did not respect the medication hours (OR = 7.38, 95%CI = 1.56–34.90, p = 0.012) and eleven times higher in patients with none or primary school education (OR = 11.38, 95% CI = 2.41–53.76, p = 0.002).ConclusionLow education level and poor adherence are the main risk factors for VF. Strengthening therapeutic failure prevention strategies and routine VL surveillance would allow early detection of VF and contribute in achieving the third goal of UNAIDS which recommends “90–90-90” targets for People Living with HIV in resource-limited settings.

Is the rate of virological failure to cART continuing to decline in recent calendar years?

BackgroundDespite the high rate of virological success of combined antiretroviral therapy (cART), HIV infected individuals continue to fail. In this contest, it is unclear whether having previously experienced virological failure (VF) of cART remains an important predictor of future risk of VF in people receiving cART in modern times. We investigated the rate of VF and factors potentially associated with this event in 9220 HIV-1 infected patients enrolled in the Icona Cohort who showed a stable viral suppression on modern cART regimens after January 1, 2006. MethodsWe investigated two main exposure factors: current calendar period (2006–2009; 2010–2013; 2014–2017) and number of VFs (0; 1–3; >3) prior to baseline. Relative rates of VF were estimated from fitting a Poisson regression model. ResultsSeven-hundred-seventy-nine patients experienced VF over follow-up for an overall rate of 2.08 per 100 person years of follow-up (PYFU, 95%CI: 1.93–2.22). The rate of VF increased with higher numbers of previous VFs: patients with >3 previous VFs had a rate of 4.87 (4.10–5.78), 2.75-fold higher than that observed in patients without any previous VF (p < 0.001). The rate of VF was lower in recent years: 3.81 (3.36, 4.32) in 2006–2009; 1.36 (1.20–1.53) in 2014–2017 (p < 0.001). Other factors independently associated with lower risk of VF were Italian origin, longer history of virological suppression, and university education level. ConclusionsIn HIV-infected patients virologically suppressed after January 2006, the rate of VF continues to show a decline even in the most recent years. Previous VFs should be carefully considered.

The Impacts of Residential Location on the Risk of HIV Virologic Failure Among ART Users in Durban, South Africa.

Using a case-control study of patients receiving antiretroviral treatment (ART) in 2010-2012 at McCord Hospital in Durban, South Africa, we sought to understand how residential locations impact patients' risk of virologic failure (VF). Using generalized estimating equations to fit logistic regression models, we estimated the associations of VF with socioeconomic status (SES) and geographic access to care. We then determined whether neighborhood-level poverty modifies the association between individual-level SES and VF. Automobile ownership for men and having non-spouse family members pay medical care for women remained independently associated with increased odds of VF for patients dwelling in moderately and severely poor neighborhoods. Closer geographic proximity to medical care was positively associated with VF among men, while higher neighborhood-level poverty was positively associated with VF among women. The programmatic implications of our findings include developing ART adherence interventions that address the role of gender in both the socioeconomic and geographical contexts.

Brief Report: Syphilis Coinfection Is Not Associated With an Increased Risk of Virologic Failure Among HIV-Positive Men Who Have Sex With Men on Antiretroviral Therapy.

Incidence of syphilis continues to increase among HIV-positive men who have sex with men (MSM) in Ontario. Our objective was to determine the effect of acute syphilis on virologic failure (VF) among virally suppressed HIV-positive MSM taking antiretroviral therapy (ART) and determine if the relationship is confounded by drug use. The OHTN Cohort Study is a voluntary cohort of people receiving HIV care in Ontario. Syphilis and viral load (VL) data were retrieved via linkage with the provincial laboratory. Analyses included 2632 MSM from 2008 to 2015, on ART, with ≥1 questionnaire and 2 consecutive VL of <50 copies per milliliter 6 months apart. VF was defined as (1) VL of ≥1000 copies per milliliter or (2) 2 consecutive VLs of ≥200 copies per milliliter ≥1 month apart. We modeled acute syphilis as a time-varying covariate on VF using Poisson regression. Time-varying drug use was assessed for confounding using an iterative process where potential confounders were removed and then reintroduced into the model. Our model allowed for repeat observations using generalized estimating equations. VF incidence was 3.5 per 100 person-years [95% confidence interval (CI): 3.4 to 4.2]. The rate ratio for VF for acute syphilis was 1.5 (95% CI: 0.9 to 2.4) in the unadjusted model; 1.6 (95% CI: 1.0 to 2.4) in the model adjusted for age, education, region, and income; and 1.2 (95% CI: 0.7 to 1.9) in the final model with additional adjustment for drug use. Acute syphilis was not associated with VF among virologically suppressed MSM on ART. Consequently, ART may still reduce HIV transmission risk to sexual partners.

Copy-Years Viremia and Risk of Virological Failure in Long-Term-Treated HIV Patients.

Viremia copy-years (VCY) is associated with mortality and disease outcome prediction. This study evaluated the association of VCY with virological failure (VF), defined as a plasma viral load (pVL) >400 copies/mL, and with single levels of viremia. Eight hundred and fifty antiretroviral therapy (ART)-treated patients with pVL < 37 copies/mL [target not detected or target detected (TD)] or >37, but less than 200 copies/mL (low-level viremia), and at least 6-pVL measures during 54 months of follow-up were selected. VCY was calculated individually over the follow-up as the area under pVL curve. Pearson's χ test was used to analyze differences in VCY quartiles distribution between groups. Higher VCY values were detected in patients with low-level viremia {294 copy-years [interquartile range (IQR): 99-1870]} than in TD [52 copy-years (IQR: 53-153)] and target not detected groups [19 copy-years (IQR: 8-54)]. VCY was also significantly different between patients with undetectable viremia and patients with basal pVL TD (P < 0.001). Pearson's χ test revealed a significant association between VCY and basal levels of viremia (P < 0.0001). In addition, the risk of VF rose with increasing VCY (Hazard ratio 1.01, 95% confidence interval: 1.01 to 1.02). This study revealed the association of VCY with VF and with single levels of viremia suggesting that, despite the success of ART, minimal residual viremia may cause the cumulative viral burden to rise. Full viral load suppression during ART is crucial to limit the increase in VCY.

Effectiveness of switching from protease inhibitors to dolutegravir in combination with nucleoside reverse transcriptase inhibitors as maintenance antiretroviral therapy among HIV-positive patients

Prolonged exposure to regimens containing protease inhibitors (PIs) as second-line therapy for human immunodeficiency virus (HIV) infection may have a negative impact on metabolic profiles and increase the risk of cardiovascular diseases. Real-world experience with dolutegravir (DTG)-based regimens as alternatives to PI-based regimens is limited in antiretroviral-experienced patients with previous failure or intolerance to first-line therapy. The current study included HIV-positive patients receiving PI-containing regimens with viral suppression for ≥6 months. Virological response and lipid profiles were compared between patients who were subsequently switched to DTG-based therapy plus nucleoside reverse transcriptase inhibitors (NRTIs) and those remaining on their PI-containing regimen at Week 48. In total, 189 patients were switched to DTG-based regimens and 313 remained on PI-containing regimens during the observation period. Patients in the DTG group were younger (mean age 40.0 years vs. 44.6 years) and were more likely to have a previous history of virological failure (44.4% vs. 19.5%) than those in the PI group. At Week 48, 1.1% of the DTG group and 3.8% of the PI group had virological non-response (HIV-RNA load >50 copies/mL) (difference, -2.7%, 95% CI -5.5% to 0.5%). The presence of M184V/I mutation and other NRTI resistance-associated mutations (RAMs) did not increase the risk of virological failure in either group. Patients switched to DTG-based therapy had statistically significant improvement of lipid profiles. Among virally suppressed HIV-positive patients, a switch to DTG-based therapy was non-inferior to continuation of PI-based therapy in virological effectiveness at Week 48, even in the presence of NRTI RAMs.

Pharmacokinetics and Safety of the Integrase Inhibitors Elvitegravir and Dolutegravir in Pregnant Women With HIV.

Objective: To synthesize data on the pharmacokinetics and safety of dolutegravir and elvitegravir in pregnant women living with HIV. Data Sources: A PubMed, EMBASE, Web of Science, and Google Scholar literature search (January 2010 to December 2018) was performed using the search terms dolutegravir, elvitegravir, women, pregnant*, and HIV. Additional reports were identified from conference abstracts and review of reference lists. Study Selection and Data Extraction: English-language studies reporting pharmacokinetic and/or safety data in pregnant women receiving dolutegravir or elvitegravir/cobicistat were included. Data Synthesis: A total of 17 studies were selected. Studies demonstrated a modest decrease in dolutegravir concentrations in pregnancy. Preliminary data suggest an increased risk of neural tube defects when dolutegravir is used at the time of conception. Available pharmacokinetic data in pregnant women showed significantly reduced plasma concentrations of elvitegravir/cobicistat which may increase the risk of virological failure. Current guidelines recommend that dolutegravir should not be initiated in women who have the potential to become pregnant or women in their first trimester of pregnancy and elvitegravir/cobicistat should be avoided during pregnancy. Relevance to Patient Care and Clinical Practice: This review highlights pharmacokinetic and safety data for dolutegravir and elvitegravir/cobicistat in pregnant women. Clinicians need to be aware of these data to convey the risks and benefits of using these agents in women of child-bearing potential. Conclusions: Changes in guideline recommendations reflect emerging data regarding the use of dolutegravir and elvitegravir/cobicistat in pregnancy. Until further information is available, raltegravir or other first-line agents are recommended for women with HIV planning to become pregnant.

HIV virologic failure and its predictors among HIV-infected adults on antiretroviral therapy in the African Cohort Study.

IntroductionThe 2016 WHO consolidated guidelines on the use of antiretroviral drugs defines HIV virologic failure for low and middle income countries (LMIC) as plasma HIV-RNA ≥ 1000 copies/mL. We evaluated virologic failure and predictors in four African countries.Materials and methodsWe included HIV-infected participants on a WHO recommended antiretroviral therapy (ART) regimen and enrolled in the African Cohort Study between January 2013 and October 2017. Studied outcomes were virologic failure (plasma HIV-RNA ≥ 1000 copies/mL at the most recent visit), viraemia (plasma HIV-RNA ≥ 50 copies/mL at the most recent visit); and persistent viraemia (plasma HIV-RNA ≥ 50 copies/mL at two consecutive visits). Generalized linear models were used to estimate relative risks with their 95% confidence intervals.Results2054 participants were included in this analysis. Viraemia, persistent viraemia and virologic failure were observed in 396 (19.3%), 160 (7.8%) and 184 (9%) participants respectively. Of the participants with persistent viraemia, only 57.5% (92/160) had confirmed virologic failure. In the multivariate analysis, attending clinical care site other than the Uganda sitebeing on 2nd line ART (aRR 1.8, 95% CI 1·28–2·66); other ART combinations not first line and not second line (aRR 3.8, 95% CI 1.18–11.9), a history of fever in the past week (aRR 3.7, 95% CI 1.69–8.05), low CD4 count (aRR 6.9, 95% CI 4.7–10.2) and missing any day of ART (aRR 1·8, 95% CI 1·27–2.57) increased the risk of virologic failure. Being on 2nd line therapy, the site where one receives care and CD4 count < 500 predicted viraemia, persistent viraemia and virologic failure.ConclusionIn conclusion, these findings demonstrate that HIV-infected patients established on ART for more than six months in the African setting frequently experienced viraemia while continuing to be on ART. The findings also show that being on second line, low CD4 count, missing any day of ART and history of fever in the past week remain important predictors of virologic failure that should trigger intensified adherence counselling especially in the absence of reliable or readily available viral load monitoring. Finally, clinical care sites are different calling for further analyses to elucidate on the unique features of these sites.