Achievement Of Viral Suppression Research Articles

Improving HIV testing, linkage, and retention in care among South African men through U = U messaging: A study protocol for two sequential hybrid type 1 effectiveness-implementation randomized controlled trials.

Increasing HIV testing and treatment coverage among people living with HIV (PLHIV) is essential for achieving global HIV epidemic control. However, compared to women, cis-gender heterosexual men living with HIV are significantly less likely to know their HIV status, initiate anti-retroviral therapy (ART) and achieve viral suppression. This is particularly true in South Africa, where men are also at increased risk of mortality resulting from AIDS-related illnesses. While there is growing knowledge of Treatment as Prevention or the concept Undetectable = Untransmittable (U = U) among PLHIV in Western and high-income countries, the reach and penetration of the U = U message in sub-Saharan Africa remains limited, and few studies have evaluated the impact of accessible and relatable U = U messages on ART initiation and adherence. To address these gaps, rigorous evaluations of interventions that incorporate U = U messages are needed, especially among men in high prevalence settings. Building on our U = U messages that we previously developed for men using behavioral economics insights and a human-centered design, we will conduct two sequential hybrid type 1 effectiveness-implementation trials to evaluate the impact of U = U messages on men's uptake of community-based HIV testing and ART initiation (Trial 1), and retention in care and achievement of viral suppression (Trial 2). For trial 1, a cluster randomized trial will be implemented with HIV testing service site-days (each day at one testing site) randomized to U = U or standard-of-care (SoC) messages inviting men to test for HIV. For trial 2, an individual-level randomized control trial will be implemented, with men initiating ART at six government clinics randomized to receive U = U counselling or SoC treatment adherence messaging. We will incorporate a multi-method evaluation to inform future implementation of U = U messaging interventions. The study will be conducted in the Buffalo City Metro Health District of the Eastern Cape Province and in the Cape Town Metro Health District in the Western Cape Province in South Africa. These trials are the first to rigorously evaluate the impact of U = U messaging on HIV testing uptake, ART initiation and achievement of viral suppression among African men. If effective, these messaging interventions can shape global HIV testing, treatment and adherence counselling guidelines and practices.

Enabling Adherence to Treatment (EAT): a pilot study of a combination intervention to improve HIV treatment outcomes among street-connected individuals in western Kenya

BackgroundStreet-connected individuals (SCI) in Kenya experience barriers to accessing HIV care. This pilot study provides proof-of-concept for Enabling Adherence to Treatment (EAT), a combination intervention providing modified directly observed therapy (mDOT), daily meals, and peer navigation services to SCI living with HIV or requiring therapy for other conditions (e.g. tuberculosis). The goal of the EAT intervention was to improve engagement in HIV care and viral suppression among SCI living with HIV in an urban setting in Kenya.MethodsThis pilot study used a single group, pre/post-test design, and enrolled a convenience sample of self-identified SCI of any age. Participants were able to access free hot meals, peer navigation services, and mDOT 6 days per week. We carried out descriptive statistics to characterize participants’ engagement in EAT and HIV treatment outcomes. We used McNemar’s chi-square test to calculate unadjusted differences in HIV outcomes pre- and post-intervention among participants enrolled in HIV care prior to EAT. We compared unadjusted time to initiation of antiretroviral therapy (ART) and first episode of viral load (VL) suppression among participants enrolled in HIV care prior to EAT vs. concurrently with EAT using the Wilcoxon rank sum test. Statistical significance was defined as p < 0.05. We calculated total, fixed, and variable costs of the intervention.ResultsBetween July 2018 and February 2020, EAT enrolled 87 participants: 46 (53%) female and 75 (86%) living with HIV. At baseline, 60 out of 75 participants living with HIV (80%) had previously enrolled in HIV care. Out of 60, 56 (93%) had initiated ART, 44 (73%) were active in care, and 25 (42%) were virally suppressed (VL < 1000 copies/mL) at their last VL measure in the 19 months before EAT. After 19 months of follow-up, all 75 participants living with HIV had enrolled in HIV care and initiated ART, 65 (87%) were active in care, and 44 (59%) were virally suppressed at their last VL measure. Among the participants who were enrolled in HIV care before EAT, there was a significant increase in the proportion who were active in HIV care and virally suppressed at their last VL measure during EAT enrollment compared to before EAT enrollment. Participants who enrolled in HIV care concurrently with EAT had a significantly shorter time to initiation of ART and first episode of viral suppression compared to participants who enrolled in HIV care prior to EAT. The total cost of the intervention over 19 months was USD $57,448.64. Fixed costs were USD $3623.04 and variable costs were USD $63.75/month/participant.ConclusionsThis pilot study provided proof of concept that EAT, a combination intervention providing mDOT, food, and peer navigation services, was feasible to implement and may support engagement in HIV care and achievement of viral suppression among SCI living with HIV in an urban setting in Kenya. Future work should focus on controlled trials of EAT, assessments of feasibility in other contexts, and cost-effectiveness studies.

Effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in HIV late presenters

The efficacy of BIC/FTC/TAF in HIV late presenters initiating antiretroviral therapy (ART) has not been sufficiently evaluated. The aim of this study was to assess the effectiveness and tolerability of BIC/FTC/TAF compared to other first-line antiretroviral regimens in treatment-naïve adult individuals from the CoRIS Cohort starting ART with CD4 counts <200 cells/mm3 and/or AIDS-defining conditions between January 1st 2019 and November 30th 2020. Logistic regression models were used to estimate odds ratios (ORs) of association between initial regimen and achievement of viral suppression (VS) (primary objective), defined as HIV RNA <50 cop/mL, and immunological recovery (IR) (secondary objective), defined as CD4 count >200 cells/mm3, at weeks 24 and 48 after initiation of ART. We evaluated 314 individuals (84.7% men, median age 40 years). Of them, 158 initiated with BIC/FTC/TAF. At inclusion, 117 had an AIDS-defining condition. In multivariable analyses, individuals with AIDS-defining conditions initiating ART with BIC/FTC/TAF achieved higher rates of VS at 24 weeks than other regimens (aOR: 0.2; 95% CI: 0.06-0.64) and, at 48 weeks, than DTG/ABC/3TC (aOR: 0.06; 95% CI: 0.01-0.76) and DTG+TDF/3TC (aOR: 0.2; 95% CI: 0.47-0.9). No other differences in VS or IR were observed. At 24 and 48 weeks after ART initiation, treatment discontinuations were lower with BIC/FTC/TAF than with other regimens (3.2% and 7.6% vs. 24.4% and 37.8%, respectively; P < 0.005). Our results suggest that BIC/FTC/TAF could be a preferred regimen as initial therapy in HIV late presenters because of its high effectiveness and good tolerability.

Cascade of care and rapid treatment pathway at Auckland City Hospital for patients with a new diagnosis of HIV infection, 2015-2019.

Legislative changes in 2017 enabled subsidised HIV care for all people living with HIV in New Zealand. This enabled a rapid treatment pathway (RTP) to be developed at Auckland City Hospital (ACH). Our aims were to document the cascade of care for people referred with newly diagnosed HIV infection and evaluate the effect of the RTP. People with newly diagnosed HIV infection in New Zealand referred to ACH between 2015 and 2019 were included in the cascade of care. The 2-year periods before (2015 and 2016) and after (2018 and 2019) the RTP were compared for initiation of antiretroviral therapy (ART) and attainment of HIV viral suppression. There were 240 people with newly diagnosed HIV infection referred. Of these, 197/200 (98.5%) were on ART and 195/197 (99%) had documented viral suppression. ART was initiated within 6 weeks of referral for 41/120 (34.2%) in the pre-RTP and 76/79 (96.2%) in the RTP periods (p<0.0001). Viral suppression was achieved within 6 months of diagnosis for 66/118 (55.9%) in the pre-RTP and 73/75 (97.3%) in the RTP periods (p<0.0001). A high proportion of people referred with newly diagnosed HIV infection were commenced on ART and achieved viral suppression. The RTP facilitated earlier initiation of ART and achievement of viral suppression.

Peer Case Management Promoting Advancement Along the HIV Care Continuum Among Black Men Who Have Sex with Men Living with HIV: Building Brothers Up.

Black men who have sex with men (BMSM) in the United States are at elevated risk for HIV relative to their heterosexual and/or non-BMSM counterparts, yet on average demonstrate suboptimal HIV care linkage and rates of HIV primary care retention. From October 2019 to December 2020, 69 adult (i.e., aged 18–65) BMSM enrolled in Building Brothers Up (2BU), a 6-session peer case management intervention delivered across 3 months and designed to improve retention in HIV primary care through to full viral suppression. Peer case management sessions included detailed assessment of participants' needs and barriers to treatment, which led to the development of a participant-centered treatment plan. All participants self-identified as Black, about three-quarters self-identified as gay (72.5%), and 46.4% reported an annual income of $5000 or less. A total of 69 participants enrolled in 2BU; however, multiply imputed chained equation logistic regressions were carried out on the final analytical data set (n = 40; 99 imputations) due to a large amount of COVID-19-related missing data. Although analyses of retention and achievement of viral suppression did not reach full significance, the probability of a Type-II hypothesis testing error was high, and viral load results (adjusted odds ratio = 1.56; 95% confidence interval = 0.94–2.60; p = 0.08) suggested that increased attendance to peer case management sessions may be associated with improved odds of achieving full viral suppression among BMSM. The significant impact of national race-related civil unrest and the COVID-19 pandemic on the target population during implementation of 2BU is underscored.

Two or more significant life-events in 6-months are associated with lower rates of HIV treatment and virologic suppression among youth with HIV in Uganda and Kenya

ABSTRACT Youth living with HIV in sub-Saharan Africa have poor HIV care outcomes. We determined the association of recent significant life-events with HIV antiretroviral treatment (ART) initiation and HIV viral suppression in youth aged 15–24 years living with HIV in rural Kenya and Uganda. This was a cross-sectional analysis of 995 youth enrolled in the SEARCH Youth study. At baseline, providers assessed recent (within 6 months) life-events, defined as changes in schooling/employment, residence, partnerships, sickness, incarceration status, family strife or death, and birth/pregnancy, self-reported alcohol use, being a parent, and HIV-status disclosure. We examined the frequencies of events and their association with ART status and HIV viral suppression (<400 copies/ul). Recent significant life-events were prevalent (57.7%). Having >2 significant life-events (aOR = 0.61, 95% CI:0.45-0.85) and consuming alcohol (aOR = 0.61, 95% CI:0.43-0.87) were associated with a lower odds of HIV viral suppression, while disclosure of HIV-status to partner (aOR = 2.39, 95% CI:1.6-3.5) or to family (aOR = 1.86, 95% CI:1.3-2.7), being a parent (aOR = 1.8, 95% CI:1.2-2.5), and being single (aOR = 1.6, 95% CI:1.3-2.1) had a higher odds. This suggest that two or more recent life-events and alcohol use are key barriers to ART initiation and achievement of viral suppression among youth living with HIV in rural East Africa. Trial registration: ClinicalTrials.gov identifier: NCT03848728..

Longitudinal Improvements in Viral Suppression for Persons With New HIV Diagnosis Receiving Care in the Ryan White Program: A 10-Year Experience in New Haven, CT (2009-2018).

BackgroundThe Ryan White (RW) program funds medical and other support services for low-income persons with HIV, significantly improving progress along the HIV care continuum. Although the program has shown overall improvements in achievement of viral suppression, the relative contributions of changes in clinical practice and RW service components to the optimization of the HIV care continuum, particularly for those with new HIV diagnoses, remain unknown.MethodsThe target population was patients with recent HIV diagnoses who received care at RW-funded clinics in the greater New Haven area between 2009 and 2018. Client data were extracted from the RW-funded database, CAREWare, and the electronic medical record. Primary outcomes included time between HIV diagnosis and first HIV primary care (PC) visit, antiretroviral therapy (ART) initiation, and viral suppression (VS).ResultsThere were 386 eligible patients. Between 2009 and 2018, the median number of days from HIV diagnosis to first PC visit decreased from 58.5 to 8.5 days, and ART initiation decreased from 155 to 9 days. In 2018, 86% of participants achieved viral suppression within 1 year, compared with 2.5% in 2009. Patients who initiated single-tablet ART and integrase inhibitor–containing regimens were more likely to reach viral suppression within 1 year (P < .001). Receipt of medical case management services was also associated with achieving viral suppression (P < .001).ConclusionsLongitudinal improvements over 10 years in ART initiation and viral suppression were observed due to clinical advances and their effective implementation through the RW comprehensive care model. Further study of the essential components promoting these outcomes is needed.

The CombinADO study to assess the impact of a combination intervention strategy on viral suppression, antiretroviral therapy adherence, and retention in HIV care among adolescents and young people living with HIV: protocol for a cluster-randomized controlled trial

BackgroundAdolescents and youth living with HIV (AYAHIV) have worse HIV outcomes than other age groups, particularly in sub-Saharan Africa (SSA). AYAHIV in SSA face formidable health system, interpersonal- and individual-level barriers to retention in HIV care, uptake of ART, and achievement of viral suppression (VS), underscoring an urgent need for multi-component interventions to address these challenges. This cluster-randomized control trial (cRCT) aims to evaluate the effectiveness and monitor implementation of a community-informed multi-component intervention (“CombinADO strategy”) addressing individual-, facility-, and community-level factors to improve health outcomes for AYAHIV.MethodsThis trial will be conducted in 12 clinics in Nampula Province, Northern Mozambique. All clinics will implement an optimized standard of care (control) including (1) billboards/posters and radio shows, (2) healthcare worker (HCW) training, (3) one-stop adolescent and youth-friendly services, (4) information/motivation walls, (5) pill containers, and (6) tools to be used by HCW during clinical visits. The CombinADO strategy (intervention) will be superadded to control conditions at 6 randomly selected clinics. It will include five additional components: (1) peer support, (2) informational/motivational video, (3) support groups for AYAHIV caregivers, (4) AYAHIV support groups, and (5) mental health screening and linkage to adolescent-focused mental health support. The study conditions will be in place for 12 months; all AYAHIV (ages 10–24 years, on ART) seeking care in the participating sites will be exposed to either the control or intervention condition based on the clinic they attend. The primary outcome is VS (viral load < 50 copies/mL) at 12 months among AYAHIV attending participating clinics. Secondary outcomes include ART adherence (self-reported and TDF levels) and retention in care (engagement in the preceding 90 days). Uptake, feasibility, acceptability, and fidelity of the CombinADO strategy during implementation will be measured. Trial outcomes will be assessed in AYAHIV, caregivers, healthcare workers, and key informants. Statistical analyses will be conducted and reported in line with CONSORT guidelines for cRCTs.DiscussionThe CombinADO study will provide evidence on effectiveness and inform implementation of a novel community-informed multi-component intervention to improve retention, adherence, and VS among AYAHIV. If found effective, results will strengthen the rationale for scale up in SSA.Trial registrationClinicalTrials.gov NCT04930367. Registered on 18 June 2021

Effect of community-based interventions targeting female sex workers along the HIV care cascade in sub-Saharan Africa: a systematic review and meta-analysis

BackgroundFemale sex workers are extremely vulnerable and highly susceptible to being infected with human immunodeficiency virus. As a result, community-based targeted interventions have been recommended as one of the models of care to improve access to HIV services and continued engagement in care. We conducted a systematic review to (1) assess the effect of FSW-targeted community interventions on the improvement of HIV services access along the treatment cascade and (2) describe community-based interventions that positively affect continuation in HIV care across the HIV treatment cascade for FSWs in sub-Saharan Africa.MethodsWe defined the 5 steps that make up the HIV care cascade and categorized them as outcomes, namely, HIV testing and diagnosis, linkage to care, receipt of ART, and achievement of viral suppression. We conducted a systematic search of randomized controlled trials, cohort, and cross-sectional studies done in sub-Saharan African countries and published from 2004 to 2020. The period was selected based on the time span within which ART was scaled up through widespread roll-out of comprehensive HIV programs in sub-Saharan Africa. We reviewed studies with data on the implementation of community interventions for any of the HIV care cascade stage. The data were analyzed using random effects meta-analysis where possible, and for the rest of the studies, data were synthesized using summary statistics.ResultsThe significant impact of the community interventions was observed on HIV testing, HIV diagnosis, and ART use. However, for HIV testing and ART use, the improvement was not sustained for the entire period of implementation. There were minimal interventions that had impact on HIV diagnosis, with only one community service delivery model showing significance. Generally, the interventions that had reasonable impact are those that implemented targeted and comprehensive package of HIV services provided at one location, and with unique strategies specific to each cascade stage.ConclusionsThe evidence brought forward from this review shows that the effect of community-based interventions varies across the different stages of HIV care cascade. A broad package of interventions including a combination of behavioral, biomedical, and structural, designed with specific strategies, unique to each cascade stage appears to be more effective, although information on long-term treatment outcomes and the extent to which FSWs remain engaged in care is sparse. There is need to conduct a further research to deepen the assessment of the effectiveness of community-based interventions on HIV care cascade for FSWs. This will enhance identification of evidence-based optimal interventions that will guide effective allocation of scarce resources for strategies that would have a significant impact on HIV service delivery.Systematic review registrationPROSPERO CRD42020157623

Health information technology interventions and engagement in HIV care and achievement of viral suppression in publicly funded settings in the US: A cost-effectiveness analysis.

BackgroundThe US National HIV/AIDS Strategy (NHAS) emphasizes the use of technology to facilitate coordination of comprehensive care for people with HIV. We examined cost-effectiveness from the health system perspective of 6 health information technology (HIT) interventions implemented during 2008 to 2012 in a Ryan White HIV/AIDS Program (RWHAP) Special Projects of National Significance (SPNS) Program demonstration project.Methods/findingsHIT interventions were implemented at 6 sites: Bronx, New York; Durham, North Carolina; Long Beach, California; New Orleans, Louisiana; New York, New York (2 sites); and Paterson, New Jersey. These interventions included: (1) use of HIV surveillance data to identify out-of-care individuals; (2) extension of access to electronic health records (EHRs) to support service providers; (3) use of electronic laboratory ordering and prescribing; and (4) development of a patient portal. We employed standard microcosting techniques to estimate costs (in 2018 US dollars) associated with intervention implementation. Data from a sample of electronic patient records from each demonstration site were analyzed to compare prescription of antiretroviral therapy (ART), CD4 cell counts, and suppression of viral load, before and after implementation of interventions. Markov models were used to estimate additional healthcare costs and quality-adjusted life-years saved as a result of each intervention. Overall, demonstration site interventions cost $3,913,313 (range = $287,682 to $998,201) among 3,110 individuals (range = 258 to 1,181) over 3 years. Changes in the proportion of patients prescribed ART ranged from a decrease from 87.0% to 72.7% at Site 4 to an increase from 74.6% to 94.2% at Site 6; changes in the proportion of patients with 0 to 200 CD4 cells/mm3 ranged from a decrease from 20.2% to 11.0% in Site 6 to an increase from 16.7% to 30.2% in Site 2; and changes in the proportion of patients with undetectable viral load ranged from a decrease from 84.6% to 46.0% in Site 1 to an increase from 67.0% to 69.9% in Site 5. Four of the 6 interventions—including use of HIV surveillance data to identify out-of-care individuals, use of electronic laboratory ordering and prescribing, and development of a patient portal—were not only cost-effective but also cost saving ($6.87 to $14.91 saved per dollar invested). In contrast, the 2 interventions that extended access to EHRs to support service providers were not effective and, therefore, not cost-effective. Most interventions remained either cost-saving or not cost-effective under all sensitivity analysis scenarios. The intervention that used HIV surveillance data to identify out-of-care individuals was no longer cost-saving when the effect of HIV on an individual’s health status was reduced and when the natural progression of HIV was increased. The results of this study are limited in that we did not have contemporaneous controls for each intervention; thus, we are only able to assess sites against themselves at baseline and not against standard of care during the same time period.ConclusionsThese results provide additional support for the use of HIT as a tool to enhance rapid and effective treatment of HIV to achieve sustained viral suppression. HIT has the potential to increase utilization of services, improve health outcomes, and reduce subsequent transmission of HIV.

Rapid ART start in early HIV infection: Time to viral load suppression and retention in care in a London cohort.

Rapid antiretroviral therapy (ART) initiation is recommended in early HIV infection (EHI), even in the absence of baseline viral resistance test result. We analysed time to viral suppression according to ART regimen started in a cohort of patients diagnosed with EHI. Clinical records of individuals consecutively diagnosed with EHI between July 2016-June 2018 were reviewed. The distribution of clinical, virological and immunological factors was compared in treatment groups using the Mann-Whitney U-test. 262 individuals (97% MSM) were diagnosed with EHI. 58% of patients agreed to start ART within 14 days of diagnosis. Tenofovir-based combinations were prescribed to all patients. DRV/b was the most commonly prescribed third agent (78%), when genotypic resistance testing was not available at time of ART choice. Switching to INSTI was encouraged once VRT became available and 27% switched from DRV/b to INSTI (mainly RAL) within 28 days from ART start. Those receiving INSTI were more likely to have a baseline viral load exceeding 1 million HIV-1 RNA copies/mL compared with those starting with DRV/b. Rapid start with INSTI regimens resulted in quicker viral suppression than when DRV/b was chosen in EHI, even when that was subsequently switched to INSTI. Retention in care following rapid ART start was achieved by all patients at 24 weeks. Starting an INSTI-based ART combination was associated with quicker viral suppression than when a protease inhibitor-based combination was chosen. No differences in the achievement of viral suppression or in retention in care were observed.

Toward Better HIV Care: A Thought Leader Interview.

The two largest providers of HIV care in the US are the Veterans Administration and Kaiser Permanente. Both organizations are significantly outperforming the general population in implementing the HIV Care Continuum, which involves 1) testing and diagnosis, 2) linkage to care, 3) retention in care, 4) initiation and continuation of antiretroviral therapy, and 5) achievement of viral suppression. Adherence to the care continuum allows people living with HIV to achieve viral suppression to levels where the virus is undetectable. Such individuals are less likely to transmit the virus than are other infected individuals not receiving medical care. In this interview article, leaders from the two comprehensive integrated health care systems share insight about how their organizations achieve top-quality HIV care outcomes, as well as their ongoing efforts to identify and close gaps in care.

Impact of Tablet Burden and Antiretroviral Therapy (ART) Choice on Virologic Outcomes in Treatment Naive HIV+ Individuals Attending an Inner City Clinic

BackgroundThe durability and effectiveness of single tablet regimens (STR) in treating ART naïve patients in real world, inner city settings, has not been well established.MethodsData was abstracted from administrative/medical records at Henry Ford Health System, serving metropolitan Detroit, for HIV+ patients initiating ART (1/1/2007–9/30/2015), who were enrolled in the Health Alliance Plan (HAP) or had ≥1 clinician contact per year and ≥1 viral load (VL)/CD4 test result ≤90 days prior to ART initiation. Patients were followed from initiation to first of: change in ART, death, HAP disenrollment, study end (03/31/2016), or lost to follow-up. Cox regression estimated impact of tablet burden on ART regimen duration, achievement of viral suppression (VS) and viral failure—(VF) failure to suppress plasma HIV RNA to <50 copies/mL or rebound after VS.ResultsAmong 390 eligible patients, 79% were male, 74% African-American. Median (IQR) age was 37 years (27–47), 49% MSM and 22% presented with AIDS. The majority (65%) initiated on an STR; 35% on multiple tablet regimens (MTR). The majority of STR initiators (63%) began with EFV/FTC/TDF; 24% with EVG/c/FTC/TDF; and 8% with DTG/ABC/3TC. The most frequent MTR were DRV+RTV+TDF/FTC (26%) and ATV+RTV+TDF/FTC (20%). Median (IQR) log10 VL at baseline was 4.8 (4.3–5.2) in STR; 4.8 (4.4–5.4) in MTR cohorts. Median CD4 cells/µL (IQR) was 277 (115–407) in STR; 231 (37–371) in MTR. VL suppression occurred in 81% (85% STR, 74% MTR, P < 0.01) of patients and in 91% of INSTI regimens (91% STR, 90% MTR, P = 0.757).VF occurred in 19% (15% STR, 25% MTR, P = 0.015) and in 10% of INSTI regimens (9% STR, 13% MTR, P = 0.459). Resistance occurred in 15% of VF patients, predominantly with NNRTI mutations. A total of 22% of STR and 60% of MTR initiators experienced a change in their initial ART regimen (P < 0.0001). Cox model results suggest STR initiators were 59% less likely to experience regimen change (P < 0.0001), 46% less likely to experience VF (P < 0.05) and 30% more likely to achieve viral suppression (P < 0.05) compared with MTR initiators.ConclusionInner city, HIV treatment naïve patients, initiating ART with a STR are significantly more likely to achieve viral suppression and less likely to experience a change in ART regimen.Disclosures B. Tidwell, ViiV Healthcare: Research Contractor, Research support; L. Lamerato, ViiV Healthcare: Collaborator, Research support; S. Zelt, ViiV Healthcare: Employee and Shareholder, Salary and Stock; R. D’Amico, ViiV Healthcare: Employee and Shareholder, Salary and Stock; K. Schulman, ViiV Healthcare: Research Contractor, Research support

Comparison of Time to Viral Suppression Among Treatment-Naïve HIV-Infected Adults Initiating Combination Antiretroviral Therapy by Antiretroviral Regimen Class

BackgroundAntiretroviral therapy (ART) regimens for the treatment of HIV that incorporate the integrase strand inhibitor (INSTI) class of antiretroviral medications have high efficacy and tolerability, and may result in faster time to virologic suppression compared with regimens that contain protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, differences in viral suppression are not well-defined in routine clinical settings.MethodsWe performed a retrospective single-center chart review of treatment-naïve HIV patients initiating ART between 2013 and 2016. Among patients on different ART regimen types, we compared rates of achievement of viral suppression (defined as viral load less than limit of detection or <20 copies/uL) over time and median time to viral suppression using chi-square and independent samples median testing. Patients who were prescribed nonstandard regimens, were nonadherent, or discontinued or changed ART within 6 months were excluded.ResultsOne hundred and fifty-five patients—45 (29.0%) female and 110 (71%) male—met study inclusion criteria. Mean age at ART initiation was 41.3 years (SD 12.5), and mean baseline viral load was 293,974 copies/uL. Twelve (7.7%) patients had an opportunistic infection diagnosed at time of ART initiation. Seventy-one (45.8%) initiated an INSTI-based ART regimen, 58 (37.4%) initiated a NNRTI-based regimen, and 26 (16.8%) initiated a PI-based regimen. Eighty-one (52.3%) patients had documented viral suppression, with median time to viral suppression 105 days (IQR 49–159). Patients on INSTI regimens were more likely to achieve viral suppression by 6 months (93.2% compared with 69.7% on NNRTIs and 30.8% on PIs), and had lower median time to suppression (62.6 days vs. 140.5 days on NNRTI regimens and 154.5 days on PI regimens, P = 0.002).ConclusionIn this cohort, patients on INSTI-based ART regimens experienced higher rates of viral suppression at 6 months and shorter time from ART initiation to viral suppression. In HIV patients on INSTI-based ART regimens, virologic failure should be suspected prior to the current recommendation of 6 months.Disclosures All authors: No reported disclosures.

Effects of HIV diagnosis and enrolment in care on transmission risk of HIV-infected men who have sex with men in Hong Kong: a cross-sectional study

BackgroundThe HIV continuum of care is a framework for monitoring of health-care service targets. From a public health perspective, little is known about the changes of transmission risks of HIV-positive men who have sex with men (MSM) at different stages in the continuum. In this study we aimed to assess the effects of HIV diagnosis and enrolment in care on the transmission risk of HIV-infected MSM in Hong Kong. MethodsA questionnaire was administered to HIV-positive MSM attending the largest HIV specialist clinic in Hong Kong between October and December, 2014. Data collected included demographics, sex networking pattern, risk behaviours, and viral loads at different stages of the care continuum, following informed consent. Approval was obtained from Joint Chinese University of Hong Kong–New Territories East Cluster Clinical Research Ethics Committee (CREC). Findings345 HIV-positive MSM (median age 37 years, IQR 30–46) were recruited. Following diagnosis, sex networking through the internet and physical venues decreased, as shown by a fall in the number of visits by 14% and 23%, respectively, within a year. 74 (21%) men had no sex partners, with a median period of abstinence of 3–6 months. Consistent condom use for anal sex with regular and non-regular partners increased (p=0·001). 336 (97%) had initiated antiretroviral therapy either in the diagnosis year (160/336 [48%]) or subsequently. Viral load suppression was achieved 1 year after diagnosis (IQR 1–3 years), a status attained by 277 (80%) at the time of study. For those whose treatment were started more than 2 years before the survey (n=82), almost all (81 [99%]) had visited sex networking venues and 44 (54%) had engaged in unprotected anal sex within a year after treatment initiation. InterpretationDiagnosis of HIV was associated with decreased sex networking and increased condom use. With the achievement of viral suppression in a majority of MSM, a general reduction of secondary HIV-transmission risk could be inferred. However, inconsistent condom use and sex networking after treatment initiation could predispose to the spread of sexually transmitted infections both within and between different MSM networks. FundingCouncil for the AIDS Trust Fund, Hong Kong Special Administrative Region Government (project code MSS230R).

Structural equation modelling of viral tropism reveals its impact on achieving viral suppression within 6 months in treatment-naive HIV-1-infected patients after combination antiretroviral therapy.

To evaluate the role of pre-treatment co-receptor tropism of plasma HIV on the achievement of viral suppression (plasma HIV RNA 1.69 log10 copies/mL) at the sixth month of combination antiretroviral therapy (cART) in a cohort of naive patients using, for the first time in this context, a path analysis (PA) approach. Adult patients with chronic infection by subtype B HIV-1 were consecutively enrolled from the start of first-line cART (T0). Genotypic analysis of viral tropism was performed on plasma and interpreted using the bioinformatic tool Geno2pheno, with a false positive rate of 10%. A Bayesian network starting from the viro-immunological data at T0 and at the sixth month of treatment (T1) was set up and this model was evaluated using a PA approach. A total of 262 patients (22.1% bearing an X4 virus) were included; 178 subjects (67.9%) achieved viral suppression. A significant positive indirect effect of bearing X4 virus in plasma at T0 on log10 HIV RNA at T1 was detected (P = 0.009), the magnitude of this effect was, however, over 10-fold lower than the direct effect of log10 HIV RNA at T0 on log10 HIV RNA at T1 (P = 0.000). Moreover, a significant positive indirect effect of bearing an X4 virus on log10 HIV RNA at T0 (P = 0.003) was apparent. PA overcame the limitations implicit in common multiple regression analysis and showed the possible role of pre-treatment viral tropism at the recommended threshold on the outcome of plasma viraemia in naive patients after 6 months of therapy.

Disparities in achieving and sustaining viral suppression among a large cohort of HIV-infected persons in care – Washington, DC

ABSTRACTOne goal of the HIV care continuum is achieving viral suppression (VS), yet disparities in suppression exist among subpopulations of HIV-infected persons. We sought to identify disparities in both the ability to achieve and sustain VS among an urban cohort of HIV-infected persons in care. Data from HIV-infected persons enrolled at the 13 DC Cohort study clinical sites between January 2011 and June 2014 were analyzed. Univariate and multivariate logistic regression were conducted to identify factors associated with achieving VS (viral load < 200 copies/ml) at least once, and Kaplan–Meier (KM) curves and Cox proportional hazards models were used to identify factors associated with sustaining VS and time to virologic failure (VL ≥ 200 copies/ml after achievement of VS). Among the 4311 participants, 95.4% were either virally suppressed at study enrollment or able to achieve VS during the follow-up period. In multivariate analyses, achieving VS was significantly associated with age (aOR: 1.04; 95%CI: 1.03–1.06 per five-year increase) and having a higher CD4 (aOR: 1.05, 95% CI 1.04–1.06 per 100 cells/mm3). Patients infected through perinatal transmission were less likely to achieve VS compared to MSM patients (aOR: 0.63, 95% CI 0.51–0.79). Once achieved, most participants (74.4%) sustained VS during follow-up. Blacks and perinatally infected persons were less likely to have sustained VS in KM survival analysis (log rank chi-square p ≤ .001 for both) compared to other races and risk groups. Earlier time to failure was observed among females, Blacks, publically insured, perinatally infected, those with longer standing HIV infection, and those with diagnoses of mental health issues or depression. Among this HIV-infected cohort, most people achieved and maintained VS; however, disparities exist with regard to patient age, race, HIV transmission risk, and co-morbid conditions. Identifying populations with disparate outcomes allows for appropriate targeting of resources to improve outcomes along the care continuum.

Potential anti-inflammatory effects of maraviroc in HIV-positive patients: a pilot study of inflammation, endothelial dysfunction, and coagulation markers.

Persistent immune activation and chronic inflammation significantly contribute to non-AIDS morbidity in HIV-infected patients. The HIV inhibitor maraviroc (MVC) targets the cellular chemokine CCR5 HIV co-receptor, which is involved in important inflammatory pathways. MVC could have significant anti-inflammatory and anti-atherosclerotic effects, also reducing immune activation. We designed a pilot study to determine which plasma biomarkers of inflammation, endothelial dysfunction, and hypercoagulability were modified by MVC in 2 groups of 10 patients starting MVC-free or MVC-containing regimens. Ten age- and gender-matched healthy controls were also included. We found higher levels of all inflammatory biomarkers in HIV-infected patients compared to healthy controls. Both groups showed decreasing levels of interleukin (IL)-17, IL-10, and macrophage inflammatory protein (MIP)-1a following the achievement of viral suppression. Vascular cell adhesion molecule (VCAM)-1 levels were decreased in the MVC group and increased in the MVC-free group. In conclusion, some inflammatory biomarkers tend to decrease with the salvage regimen; MVC was not associated with a better impact on these measured markers.

Virologic outcomes of second-line antiretroviral therapy in Eastern European country of Georgia.

BackgroundData on the effectiveness of second-line antiretroviral therapy (ART) in resource-limited countries of Eastern Europe is limited. Objective of this study was to evaluate virological outcomes of second-line ART in Georgia.MethodsWe conducted retrospective analysis using routinely available program data. Study included adult HIV-infected patients with confirmed HIV drug resistance, who were switched to second-line ART from August 2005 to December 2010. Patients were followed until July 1, 2011. Primary outcome was achievement of viral suppression. Demographic, clinical, laboratory and adherence data were abstracted from medical and program records. Adherence was expressed as percentage based on medication refill data, and was calculated as days supply of medications dispensed divided by days between prescription fills. Predictors of primary outcome were assessed in modified Poisson regression analysis.ResultsA total of 84 patients were included in the study. Among them 71.4% were men and 62% had history of IDU. All patients were receiving non-nucleoside reverse transcriptase based regimen as initial ART. The mean 6-month adherence prior to virologic failure was 75%, with 31% of patients showing 100% adherence. All patients were switched to protease inhibitor based regimens. Patients were followed for median 27 months. Over this period 9 (10.7%) patients died. Among 80 patients remaining alive at least 6 month after ART regimen switch, 72 (90%) patients ever reached undetectable viral load. The mean first 6-month adherence on second-line treatment was 81%, with 47.5% of patients showing 100% adherence. The proportion of patients achieving viral suppression after 6, 12, 24 and 36 months of second-line ART did not vary significantly ranging from 79 to 83%. Percentage of IDUs achieving viral suppression ranged from 75% and 83%. Factors associated with failure to achieve viral suppression at 6-months of second-line ART were: adherence <80% (Risk ratio [RR] 5.09, 95% CI: 1.89-13.70) and viral load >100,000 at the time of treatment failure (RR 3.39, 95% CI: 1.46-7.89).ConclusionsThe study demonstrated favourable virological outcomes of the second-line ART in Georgia. Majority of patients, including IDUs, achieved sustained virological response over 36 month period. The findings highlight the need of improving adherence.

Tolerability and Efficacy of PI Versus NNRTI-Based Regimens in Subjects Receiving HAART During Acute or Early HIV Infection

Little is known about modifications to highly active antiretroviral therapy (HAART) initiated during acute or early HIV infection. Reasons for first modifications of HAART regimens were recorded using the AIDS Clinical Trials Group form among 363 subjects who initiated HAART within 1 year of seroconversion from 2005 in the Acute Infection and Early Disease Research Program. Modifications recorded as due to "patient choice" or "physician choice" were clarified by query to the recording site. Times to events were analyzed by Kaplan-Meier methods; significance of differences was assessed by the log-rank test. Two hundred five of 363 (56%) subjects modified therapy, at a median of 425 days after initiation, by changing drugs, discontinuing treatment, or removing or adding drugs. Most modifications were attributed to toxicity (n = 105, 51%), most of which was low grade; regimen simplification (n = 18, 5%); and achievement of viral suppression (n = 15, 7%). Time to first modification was shorter for those with shorter time from infection to initiation (P = 0.005) and those having higher CD4 lymphocyte count at initiation (P = 0.06). Modifications occurred sooner in subjects receiving regimens taken more than once daily (P < 0.001) or with more than 2 pills daily (P < 0.001). Most regimens were nonnucleoside reverse transcriptase inhibitor based or protease inhibitor based, and these did not differ significantly in rate and timing of modification. HAART initiated early in HIV infection was modified in the majority of cases, usually due to minor toxicities whose incidence was similar for protease inhibitor-based and nonnucleoside reverse transcriptase inhibitor-based regimens. Convenience of regimens (lower pill burden and dosing frequency) was associated with a lower rate of modification.