scholarly journals Intermittent two-drug antiretroviral therapies maintain long-term viral suppression in real life in highly experienced HIV-infected patients

2021 ◽  
Author(s):  
Romain Palich ◽  
Basma Abdi ◽  
Marc Wirden ◽  
Giota Lourida ◽  
Roland Tubiana ◽  
...  
Keyword(s):  
Success Rate ◽  
Viral Suppression ◽  
Real Life ◽  
Cd4 Count ◽  
Strand Transfer ◽  
Virological Success ◽  
Single Centre Study ◽  
Drug Regimens ◽  
Transfer Inhibitor ◽  
Residual Viraemia

Abstract Objectives To assess in real life whether two-drug regimens (2-DRs) given 4–5 days a week in virally suppressed patients can maintain viral suppression over 48 and 96 weeks. Methods This observational single-centre study enrolled all patients who initiated an intermittent 2-DR between 01/01/2016 and 30/06/2019. The primary outcome was the rate of virological failure (VF), defined as confirmed plasma viral load (pVL) ≥50 copies/mL or single pVL ≥50 copies/mL followed by ART change at week 48 (W48) and W96. Secondary outcomes were the 2-DR intermittent strategy success rate (pVL <50 copies/mL with no ART change), change in CD4 count, CD4/CD8 ratio and rate of residual viraemia. Results Eighty-five patients were included; 67/85 (79%) were men, median age = 57 years (IQR = 50–63), CD4 nadir = 233 cells/mm3 (110–327), ART duration = 21 years (13–24), duration of virological suppression = 6.5 years (3.7–10.8) and CD4 count = 658 cells/mm3 (519–867). Intermittent 2-DRs consisted of integrase strand transfer inhibitor (INSTI)/NNRTI (58%), INSTI/NRTI (13%), two NRTIs (11%), PI/NRTI (7%) and other combinations (11%). The median follow-up was 90 weeks (IQR = 64–111). Overall, four VFs occurred, leading to a virological success rate of 98.8% (95% CI = 93.6–100) at W48 and 95.3% (95% CI = 88.4–98.7) at W96. Resuming the same 2-DR 7 days a week led to viral resuppression in three patients, whereas the M184V mutation emerged in one patient, leading to ART modification. There was no significant change in the CD4 count or residual viraemia rate, but a small increase in the CD4/CD8 ratio (P = 0.009) occurred over the study period. Conclusions This observational study shows the potential for intermittent 2-DRs to maintain a high virological success rate, which should be assessed in larger prospective randomized studies.

scholarly journals Maintenance of Viral Suppression after Optimization Therapy from Etravirine Plus Raltegravir to Rilpivirine Plus Dolutegravir in HIV-1-Infected Patients

2019 ◽  
Vol 18 ◽  
pp. 232595821882165 ◽  
Author(s):  
Niccolò Riccardi ◽  
Filippo Del Puente ◽  
Lucia Taramasso ◽  
Antonio Di Biagio
Keyword(s):  
Reverse Transcriptase ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Viral Suppression ◽  
Real Life ◽  
Transcriptase Inhibitor ◽  
Strand Transfer ◽  
Immunodeficiency Virus ◽  
Transfer Inhibitor ◽  
Reverse Transcriptase Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Non-nucleoside reverse-transcriptase inhibitor plus integrase strand transfer inhibitor–based dual therapies are an attractive simplification, nucleoside reverse transcriptase inhibitor-sparing strategy for experienced human immunodeficiency virus-infected patients. Thus, we performed a 24-week real-life observational study to assess efficacy and safety of switching from raltegravir plus etravirine to dolutegravir plus rilpivirine in 7 previously heavily treated patients. This simplification strategy reduced pill burden and preserved viral suppression in treatment-experienced patients with no major mutations to rilpivirine at historical genotyping.

scholarly journals 334. Weight Change Associated with Antiretroviral Therapy Switch to Integrase Strand Transfer Inhibitor-Based Regimens

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S177-S177 ◽  
Author(s):  
Saghar Saber ◽  
Andrew B Bernstein ◽  
Andrew D Sparks ◽  
Marc O Siegel
Keyword(s):  
Weight Gain ◽  
Antiretroviral Therapy ◽  
Weight Change ◽  
Statistical Significance ◽  
Inverse Correlation ◽  
Cd4 Count ◽  
Strand Transfer ◽  
Significant Difference ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Abstract Background An association between switching antiretroviral therapy (ART) to integrase strand transfer inhibitor (INSTI)-based ART and weight gain has been previously reported. However, insufficient data exists on risk factors associated with such weight gain. Methods We reviewed charts of 119 virally-suppressed HIV-positive patients switched from nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)-based ART to INSTI-based ART and compared their weight change over 17 months to 56 virally-suppressed patients who were maintained on NNRTI-based regimens over the same period.We looked at variables associated with weight gain including age, weight, body mass index (BMI), gender, CD4 count, starting ART, and final INSTI-based ART. Results The 119 patients switched to INSTI-based ART gained an average of 6.9 lbs compared with an average 1 lbs weight gain in the 56 patients who were maintained on NNRTI-based ART (P = 0.002). There was also a statistically significant difference in the percentage % weight change between the two groups (4.2% vs. 0.7%, P < 0.001).There was an average 1.2 lbs weight loss in 92 of the 119 patients with weights recorded 17 months before switching ART, compared with an average 6.7 lbs weight gain after the switch (P < 0.001).There was no association between gender, CD4 count at the time of switch, starting ART, or final INSTI-based ART with weight gain. However, patients weighing < 150 lbs at the time of switch had a greater % weight gain than patients weighing >200 lbs (6.9% vs. 2.7%, P = 0.02) and a trend to greater % weight gain than those weighing ≥150 to ≤ 200 lbs (6.9% vs. 3.8%, P = 0.06). There was marginal statistical significance when comparing those with BMIs < 25 to those with BMIs ≥25 to ≤ 30 (8.2 vs. 6.5 lbs, P = 0.069) and those with BMIs >30 (8.2 vs. 5.0 lbs, P = 0.057). There was an inverse correlation between age and weight gain, indicating that less weight was gained when switching to INSTI-based ART as the age of the patient increased (ρ = -0.211, P = 0.021). Conclusion Our study showed a statistically significant weight gain in patients switched from NNRTI- or PI- to INSTI-based ART compared with patients maintained on NNRTI-based ART.Baseline variables associated with greater weight gain included weight <150 lbs, BMI <25 and younger age. Disclosures All authors: No reported disclosures.

Dual therapy combining raltegravir with etravirine maintains a high level of viral suppression over 96 weeks in long-term experienced HIV-infected individuals over 45 years on a PI-based regimen: results from the Phase II ANRS 163 ETRAL study

2019 ◽  
Vol 74 (9) ◽  
pp. 2742-2751 ◽  
Author(s):  
Christine Katlama ◽  
Lambert Assoumou ◽  
Marc-Antoine Valantin ◽  
Cathia Soulié ◽  
Esteban Martinez ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Success Rate ◽  
Bone Mineral ◽  
Viral Suppression ◽  
Dual Therapy ◽  
Integrase Inhibitor ◽  
Mineral Density ◽  
Type 1 Error ◽  
Virological Success ◽  
High Level

Abstract Background Dual therapy combining integrase inhibitors and NNRTIs represents a promising regimen in ageing HIV-infected individuals with long exposure to nucleoside analogues and PIs. Methods The ANRS 163 ETRAL trial (NCT02212379) was a 96 week, multicentre, single-arm study evaluating the efficacy and safety of raltegravir (400 mg twice daily)/etravirine (200 mg twice daily) in individuals >45 years, on a PI-containing regimen who were integrase inhibitor and etravirine naive. The primary endpoint was the proportion of participants with virological success, defined by the absence of virological failure up to week 48. Main secondary outcomes included evolution of metabolic parameters, CD4/CD8 count, bone mineral density and inflammatory markers. The study was designed to show an efficacy >90%, assuming a success rate ≥95%, with a power of 80% and a 5% type-1 error. Results One hundred and sixty-five participants (median age 52 years, duration of ART 16.9 years, viral suppression 6.9 years and CD4 count 700 cells/mm3) were enrolled. By ITT analysis, viral suppression was maintained in 99.4% of participants (95% CI = 95.6%–99.9%) at week 48 and 98.7% (95% CI = 95.0%–99.7%) at week 96. Two virological failures occurred (week 24 and week 64) without emergence of integrase inhibitor resistance. Eight participants discontinued raltegravir/etravirine for adverse events, leading to a strategy success rate of 95.1% (95% CI = 90.5%–97.5%) at week 48 and 92.7% (95% CI = 87.5%–95.8%) at week 96. Over 96 weeks, lipid fractions improved (P < 0.001), CD4/CD8 ratio increased, IFNγ-induced protein 10 (IP-10) decreased (−8.1%), soluble CD14 decreased (−27%, P < 0.001) bone mineral density improved and BMI increased. Conclusions Raltegravir plus etravirine dual therapy demonstrated durable efficacy in virologically suppressed ageing patients.

scholarly journals A systematic review of the genetic mechanisms of dolutegravir resistance

2019 ◽  
Vol 74 (11) ◽  
pp. 3135-3149 ◽  
Author(s):  
Soo-Yon Rhee ◽  
Philip M Grant ◽  
Philip L Tzou ◽  
Geoffrey Barrow ◽  
P Richard Harrigan ◽  
...  
Keyword(s):  
Strand Transfer ◽  
Resistance Mutations ◽  
First Line Therapy ◽  
Highly Effective ◽  
Active Viral Replication ◽  
Drug Regimens ◽  
Genetic Mechanisms ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Abstract Background Characterizing 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. Methods We 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 conclusions We 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.

Is immune recovery different depending on the use of integrase strand transfer inhibitor-, non-nucleoside reverse transcriptase- or boosted protease inhibitor-based regimens in antiretroviral-naive HIV-infected patients?

2019 ◽  
Author(s):  
Yusnelkis Milanés-Guisado ◽  
Alicia Gutiérrez-Valencia ◽  
Juan Manuel Muñoz-Pichardo ◽  
Antonio Rivero ◽  
Maria Trujillo-Rodriguez ◽  
...  
Keyword(s):  
Viral Load ◽  
Repeated Measures ◽  
Integrase Inhibitor ◽  
Undetectable Viral Load ◽  
Cd4 Count ◽  
Strand Transfer ◽  
Treatment Groups ◽  
Hiv Rna ◽  
The Third ◽  
Transfer Inhibitor

Abstract Objectives To analyse whether integrase inhibitor (InSTI)-based regimens achieve better immunological recovery than NNRTI- or boosted PI (bPI)-based regimens as initial ART. Methods In a retrospective analysis, we selected patients who initiated ART with two NRTIs plus an InSTI, an NNRTI or a bPI and maintained both the same ‘third drug’ and an HIV-RNA <50 copies/mL in ≥95% of determinations once undetectable viral load had been achieved. We compared CD4+ count, %CD4+ and CD4+/CD8+ ratio recovery over 2 years. Data were analysed using mixed-effects regression models for repeated measures. Results Of the 836 patients included, 208, 481 and 147 initiated with InSTI, NNRTI and bPI, respectively. For CD4+, %CD4+ and CD4+/CD8+ two main slopes were identified: from month 0 to month 6, with the highest increments; and from month 6 to month 24, with smaller increases every semester. Although the patients on InSTI achieved undetectable viral load faster, for CD4+ and %CD4+ there were no differences in the slopes of change according to the third drug either for the first phase (P = 0.137 and P = 0.393, respectively) or from month 6 onwards (P = 0.834 and P = 0.159, respectively). The increase in CD4+/CD8+ was slightly higher for bPI compared with InSTI (difference of 0.0119, 95% CI 0.0020–0.0205; P = 0.018), but clinically negligible. From month 6 onwards, no differences were found between treatment groups (P = 0.176). Conclusions Immune restoration measured as CD4+ count, %CD4+ and CD4+/CD8+ increases was independent of the third antiretroviral drug class used when given with two NRTIs.

Inflammatory Myositis Secondary to Anti-Retroviral Therapy in a Child; Case Report and Review of the Literature

2021 ◽  
pp. 1-7
Author(s):  
Marie Monaghan ◽  
Charlotte Loh ◽  
Stephen Jones ◽  
Agyepong Oware ◽  
Kathryn Urankar ◽  
...  
Keyword(s):  
Drug Regimen ◽  
Dramatic Improvement ◽  
Strand Transfer ◽  
Inflammatory Myositis ◽  
Once Daily ◽  
Immune Mediated ◽  
Show Evidence ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Here, we describe a five year old girl with congenital HIV who had a six-week onset of rapidly deteriorating mobility and progressive proximal muscle weakness, associated with a raised Creatine Kinase (CK) level of 4330 U/L [25–200 U/L], subsequently diagnosed with an inflammatory myositis. Potential causes were investigated by paediatric neurology and immunology teams. Her viral load had been undetectable over the preceding two years, excluding a primary HIV myositis. While MRI scanning did not show evidence of definite myositis, a muscle biopsy showed evidence of an inflammatory process, comprising a moderate endomysial, perimysial and perivascular mononuclear (CD8 + T cell) infiltrate with increased MHC expression. No particular features of dermatomyositis or immune-mediated necrotising myopathy were identified and there were no features of an inclusion body myositis. Given the absence of active HIV infection, the role of anti-retroviral medications was considered. She had had a recent switch in medication, from twice daily Raltegravir (an Integrase Strand Transfer Inhibitor, INSTI) to once daily Dolutegravir (an INSTI) while continuing on an established daily protocol of Abacavir and Lamivudine (Nucleoside Reverse Transcriptase Inhibitors). Changing the Dolutegravir back to Raltegravir, in combination with continuing Lamivudine and Abacavir for two months made no difference to her weakness or CK levels. Moreover, this drug regimen had been well-tolerated over the preceding 19 month period. Changing the anti-retroviral regime completely to a single drug class (Protease Inhibitors) of Ritonavir and Darunavir, resulted in a dramatic improvement in her symptomatology. Within ten days she regained the ability to stand and walk, with a reduction in her CK from 1700 U/L at time of switch to 403 U/L [25–200]. This case highlights the potential risk of developing inflammatory myositis from anti-retrovirals even 19 months into treatment.

scholarly journals 1010. Effective Management of HIV in Rural Georgia Using Telemedicine

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S533-S533
Author(s):  
Folake J Lawal ◽  
Arni S R Srinivasa Rao ◽  
Jose A Vazquez
Keyword(s):  
Rural Areas ◽  
Viral Suppression ◽  
Retrospective Chart Review ◽  
Cd4 Count ◽  
Hiv Care ◽  
Resistance Mutations ◽  
Remote Communities ◽  
Hiv Viral Load ◽  
Viral Control ◽  
Significant Difference

Abstract Background The increasing incidence of HIV and lack of care in rural areas contributes to the ongoing epidemic. The dearth of specialized health services within remote communities and access of this population to available services poses a challenge to HIV care. Telemedicine (TM) is a potential tool to improve HIV care in these remote communities, but little is known about its effectiveness when compared to traditional (face-to-face) (F2F) care. The objective of this study is to examine the effectiveness of HIV care delivered through TM, and compare to F2F care. Methods This is a retrospective chart review of all HIV positive patients who attended either the F2F clinic (Augusta, GA) or the TM clinic (Dublin, GA) between May 2017 to April 2018. Data extracted included demographics, CD4 count, HIV PCR, co-morbidities, dates of clinic attendance, HIV resistance mutations and ART changes. Viral suppression and gain in CD4 counts were compared. T-test was conducted to test differences in characteristics and outcomes between the two groups. Results 385 cases were included in the study (52.5% black, 82% females, F2F=200, TM=185). Mean CD4 count in the TM group was statistically higher (643.9 cells/mm3) than the F2F group (596.3 cells/mm3) (p&lt; 0.001). There was no statistically significant difference in mean HIV viral load (F2F= 416.8 cp/ml, TM=713.4 cp/ml, p=0.3) and rates of year-round viral control (F2F= 73% vs TM = 77% p= 0.54). 38 patients achieved viral suppression during the study period (F2F= 24, TM =14) with a mean change of -3.34 x 104 vs -1.24 x 104, respectively. The difference in mean change was not statistically significant by Snedacor’s W Statistics. This indicates there was no significant difference between the two populations in terms of mean viral suppression among patients who were otherwise not suppressed before the study period. Conclusion To achieve an HIV cure, HIV care is required to extend to rural areas of the country and the world. Through delivery of care using TM, trained specialists can target communities with little or no health care. Moreover, use of TM achieves target outcome measures comparable to F2F clinics. Increase in the use of TM will improve the access to specialty HIV care and help achieve control of HIV in rural communities. Disclosures All Authors: No reported disclosures

Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir

2020 ◽  
Author(s):  
Hanh T Pham ◽  
Brunna M Alves ◽  
Sunbin Yoo ◽  
Meng A Xiao ◽  
Jing Leng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dna Binding ◽  
Drug Resistant ◽  
Strand Transfer ◽  
Viral Genomes ◽  
Proviral Dna ◽  
Viral Loads ◽  
Subtype B ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Abstract Objectives The development of HIV drug resistance against the integrase strand transfer inhibitor dolutegravir is rare. We report here the transient detection, by near full-genome ultradeep sequencing, of minority HIV-1 subtype B variants bearing the S153F and R263K integrase substitutions in the proviral DNA from blood cells of one patient who successfully initiated dolutegravir-based ART, over 24 weeks. Our objective was to study the effects of these substitutions. Methods Strand transfer and DNA-binding activities of recombinant integrase proteins were measured in cell-free assays. Cell-based resistance, infectivity and replicative capacities were measured using molecular clones. Structural modelling was performed to understand experimental results. Results R263K emerged first, followed by the addition of S153F at Week 12. By Week 24, both mutations remained present, but at lower prevalence. We confirmed the coexistence of S153F and R263K on single viral genomes. Combining S153F or S153Y with R263K decreased integration and viral replicative capacity and conferred high levels of drug resistance against all integrase inhibitors. Alone, S153Y and S153F did little to infectivity or dolutegravir resistance. We identified altered DNA binding as a mechanism of resistance. The patient remained with undetectable viral loads at all timepoints. Conclusions Drug-resistant minority variants have often been reported under suppressive ART. Our study adds to these observations by unravelling a progression towards higher levels of resistance through a novel pathway despite continuous undetectable viral loads. Poorly replicative HIV drug-resistant minority proviral variants did not compromise viral suppression in one individual treated with dolutegravir.

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