ART oggi: strategie in evoluzione ed innovazione

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Acknowledgements University of Milan, Italy: C. Alteri, V. Cento, L. Colagrossi. - ASST Grande Ospedale Niguarda: S. Carta
Policlinic of Rome Tor Vergata, Rome, Italy: M. Andreoni, L. Sarmati, M. Viscione, S. Gini, C. Cerva, V. Malagnino, K. Stingone, T. Guenci, F. Stazi, S. Giannella, V. Serafini, M. Ciotti, P. Paba. S. Grelli. INMI L Spallanzani, Rome, Italy: A. Antinori, R. Bellagamba, C. Pinnetti, S. Cicalini, R. Gagliardini, A. Mondi, A. Vergori, A. Sanpaoloesi, G. De Carli, F.M. Fusco, L. Lo Iacono, M.L. Giancola, G. Liuzzi, R. Acinapura, P. Scognamiglio, N. Orchi, E. Girardi, M.R. Capobianchi, C. Gori, F. Forbici, G. Berno, D. Pizzi, A. Giannetti, P. Lorenzini, A. Navarra, R. Libertone, G. Ippolito. San Gallicano Hospital, Rome, Italy: A. Latini, M. Colafigli, M. Giuliani, A. Pacifici, A. Cristaudo. General Hospital Umberto I: V. Vullo, G. D’Ettorre, F. Falasca, O. Turriziani, G. Antonelli. San Giovanni Addolorata Hospital, Rome, Italy: F. Montella, F. Di Sora, W. Leti, F. Iebba. Sant’Andrea Hospital, Sapienza University, Rome, Italy: A. Pennica. Rebibbia, Rome, Italy: S. Marcellini. Bambin Gesù Hospital, Rome Italy: S. Bernardi, H Tchidjou Kuekou. Polo Pontino, Sapienza University, Rome, Italy: C. Mastroianni, M. Lichtner, V.S. Mercurio, C. Del Borgo, R. Marrocco. Frosinone Hospital, Frosinone, Italy: G. Farinelli, E. Anzalone, M. Limodio, L. Sarracino. Rieti Hospital, Italy: G. Natalini Raponi, M.E. Bonaventura. Viterbo Hospital, Viterbo, Italy: G. Maffongelli, G. Bernardini, A. Caterini, F. Ferri, A. Ialungo, E. Liguori, D. Migliorini, R. Monarca, R. Preziosi, E. Rastrelli, G. Starnini, G. Sebastiani. University of Turin, Turin, Italy: G. Di Perri, S. Bonora, A. Calcagno, V. Ghisetti, G. Vandemmiati, T. Allice. Modena Hospital, Modena, Italy: C. Mussini, V. Borghi, W. Gennari, A. Cossarizza, M. Nasi, M. Di Gaetano.
Pescara General Hospital, Pescara, Italy: G. Parruti, F. Vadini, F. Sozio, E. Mazzott, T. Ursini, E. Polilli, P. Di Stefano, M. Tontodonati, G. Calella. San Salvatore, L’Aquila, Italy: A. Grimaldi, A. Cellini. Ancona Hospital, Ancona, Italy: A. Mataloni Paggi. Giuseppe Mazzini Hospital, Teramo, Italy: Di Giammartino, L. Falconi, P. Tarquini. San Salvatore – Muraglia- Hospital, Pesaro, Italy: E. Petrelli, G. Corbelli, P. Tarquini. Avezzano Hospital, Avezzano, Italy: M. Paoloni, R. Mariani. AO Papa Giovanni XXIII, Bergamo, Italy: F. Maggiolo, AP Callegaro. AO Careggi, Florence, Italy: K. Sterrantino.
Cotugno Hospital, Naples, Italy: A. Chirianni, M. Gargiulo. University of Campania Vanvitelli, Italy: S. Marini, N. Coppola. Bisceglie-Trani Hospital, Bisceglie, Italy: R. Losappio. Catania Hospital, Catania, Italy: R. La Rosa. Enna Hospital, Enna, Italy: L. Guarneri. Palermo Hospital, Palermo, Italy: F. Di Lorenzo T. Prestileo, A. Cascio.
The Patients
University of Rome “Tor Vergata”, Rome Italy: F. Ceccherini Silberstein, V. Svicher, A. Bertoli, M.C. Bellocchi, L. Fabeni, B. Yagai Romeo, R. Salpini, R. Scutari, S. Barbaliscia, M. Brugneti, A. Biddittu, M. Bruni, L. Carioti, P. Saccomandi. Saint Camillus International University of Health Sciences, Rome Italy: D. Armenia.
Thanks to the modern therapies, today >90% of HIV infected individuals achieve virological suppression
Jun 2019 Report for 2019, first 6
months
HIV-RNA strata (copies/mL) in all patients in follow-up according to calendar year
6,8% 2,2%
89,2%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019
>100000
10.000-100.000
1.000-10.000
50-1.000
<=50
Major results of pivotal studies with STR- TAF/FTC vs DTG -3TC based in drug-naive HIV patients
5
Gemini Cahn et al. Lancet 2018
93% 91% 91.4% 89% 90%
Grafico1
Virological Responses @ W48
Virological Response and Resistance Profile in HIV-1 Infected Patients Starting a Darunavir Containing Regimen
Armenia et al, HIV Medicine 2016
D Armenia1, D Di Carlo1, G Maffongelli2, V Borghi3, C Alteri1, F Forbici4, A
Bertoli1,5, M Giuliani6, E Nicastri7, M Zaccarelli7, C Pinnetti7, S Cicalini7, G
D’Offizi7, F Ceccherini-Silberstein1, C Mussini3, A Antinori7, M Andreoni2,
CFPerno4, and MM Santoro1
1University of Rome Tor Vergata, Experimental Medicine and Surgery, Rome, Italy 2University Hospital Tor Vergata, Infectious Diseases Division, Rome, Italy 3Modena University Hospital, Infectious Diseases Division, Modena, Italy 4L Spallanzani Hospital, Antiretroviral Therapy Monitoring Unit, Rome, Italy 5 University Hospital Tor Vergata, Molecular Virology Division, Rome, Italy 6IRCSS San Gallicano, HIV/AIDS Unit Rome, Italy 7L Spallanzani Hospital, Infectious Diseases Division, Rome, Italy
In drug-naïve patients the median time of achieving VS under darunavir treatment significantly increased by increasing baseline viremia but there were no significant differences in the rate of virological success according to DRV/r dosage.
Armenia et al, HIV Medicine 2017
Characteristics DRV/r 600/100 mg BD DRV/r 800/100 mg QD p-value(N=39) (N=167) Male, n (%) 31 (79.5) 138 (82.6) 0.819 Median (IQR) age, year 42 (36-48) 40 (31-46) <0.001 Median (IQR) plasma HIV-RNA at baseline (log10 copies/mL) 5.6 (5.2-6.0) 5.0 (4.5-5.5) <0.001 Plasma HIV-RNA at baseline (copies/mL), n (%): <100,000 9 (23.1) 83 (49.7) 0.005 100,000-500,000 14 (35.9) 56 (33.5) 0.926 >500,000 16 (41.0) 28 (16.8) 0.002 Median (IQR) CD4 cell count at baseline (cells/µL) 174 (38-360) 285 (170-382) 0.019 B subtype, n (%) 24 (61.5) 115 (68.9) 0.491 Median (IQR) year of starting DRV/r treatment 2012 (2010-2013) 2012 (2011-2012) 0.274 Number of drugs co-administered with DRV/r, n (%): 1 4 (10.3) 21 (12.6) 1.000 2 27 (69.2) 130 (77.8) 0.353 ≥3 8 (20.5) 16 (9.6) 0.091 Novel drugs co-administered with DRV/r, n (%): RAL 11 (28.2) 32 (19.2) 0.302 T20 0 (0) 1 (0.6) 1.000 ETR 0 (0) 2 (1.2) 1.000 MVC 0 (0) 3 (1.8) 1.000 At least one PRM at baseline, n (%) 3 (7.7) 5 (3.0) 0.177 At least one DRM at baseline, n (%) 3 (7.7) 0 (0) 0.006 At least one major NRTI RM at baseline, n (%) 2 (5.1) 10 (6.0) 1.000 At least one major NNRTI RM at baseline, n (%) 9 (23.1) 14 (8.4) 0.020
ABC: abacavir. AZT: zidovudine. BD: twice daily. DRM: DRV resistance associated mutation. DRV/r: ritonavir-boosted darunavir. ETR: etravirine. FTC: emtricitabine. IQR: interquartile range. MVC: maraviroc. NNRTI: non-nucleos(t)ide reverse transcriptase inhibitor. NRTI: nucleos(t)ide reverse transcriptase inhibitor. PI: protease inhibitor. PRM: PI major resistance associated mutation. RAL: raltegravir. QD: once daily. RM: resistance mutation. T20: enfuvirtide. TDF: tenofovir. 3TC: lamivudine.
DRV600 was preferentially administered in drug-naïve patients with a more compromised situation, having at baseline older age, higher viremia, lower CD4 cell count and DRV resistance.
Armenia et al, 2017 HIV Medicine
Viral Load and CD4 cell count remain key parameters to be assessed in cART naïve
patients
October 2018
Kaplan-Meier estimates of the probability of achieving virological success at 12 months cART in patients starting an INI-based first- line therapy stratified for pre-cART viremia.
Armenia et al., 2019
In patients who start a first- line INI-based regimen, the probability of achieving virological success at 12 months is pre-ARV viremia dependent!
……..in the long-term management of HIV infection, the stable maintenance of undetectable HIV over the years is more important than the mere success of the first regimen at 12 months….
But………
0. 0
0. 2
0. 4
2600 1981 14903407 1405 1116 8591814
No. at risk
13.8% 17.6%
0.0
0.2
0.4
4
0. 0
0. 2
0. 4
2676 2071 15823407 1491 1220 9661814
No. at risk
7.6% 7.2%
14.4% 11.1%
p=0.0090.0
Pre-therapy plasma viral load(copies/mL): ≤100,000 100,001-500,000 500,001-1,000,000 >1,000,000
Italian data confirm the impact of high pre-therapy viremia (also at viremia >500,000 or >1,000,000 copies/mL) on virological rebound after the achievement of undetectability under first line treatment
Kaplan-Meier curves estimates of cumulative probability of virological rebound according to pre-HAART viremia ranges and type of first-line treatment
Kaplan-Meier cumulative probability estimates of VR (the first of two consecutive plasma viral load measurements >50 copies/mL, Panel A; the first of two consecutive plasma viral load measurements >200 copies/mL, Panel B) at four years after achieving virological suppression was performed by stratifying patients according to pre-therapy viral load ranges (copies/mL).
Armenia et al., Antivir Ther 2019
The achievement of virological success is also influenced by the levels of CD4 cell count pre-
cART!
Kaplan-Meir estimates of the probability of achieving virological success at 12 months cART in patients starting an INI-based first- line therapy stratified for pre-cART CD4 cell count.
Armenia et al., 2019
In patients who start a first-line INI-based regimen, an increased probability of achieving virological success and decreased median time of achieving virological success is found at 12 months by increasing the levels of pre-CART CD4 cell count (from 91% at <200 cells/mm3 to 99% at >500 cells/mm3).
Raffi et al., Lancet 2014
Subgroup analyses showed that the NtRTI-sparing regimen was inferior to the standard regimen in patients with baseline CD4 cell count <200 cells per μL.
The evaluation of CD4 cell count before therapy start is still today crucial, since >30% of newly diagnosed individuals has CD4 cell count <200 cells/mm3
Jun report 2019
23% 20% 22% 22% 20% 20% 17%
21% 23%
21% 18%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
<200 201-350 351-500 >500
In cART naive patients, CD4 cell count levels at the moment of baseline genotypic resistance test are stable from 2010 to 2018
Analysis performed on 4411 cART naïve patients at the moment of baseline GRT before starting cART from 2010 to 2018 (update August 2018). Pvalue by chi Squared for trend test and Klushall-Wallis test
346 (163-518)
334 (138-531)
318 (137-499)
318 (151-506)
348 (159-531)
337 (151-535)
376 (162-585)
329 (134-528)
307 (119-487)
Year of GRT (N)
Variables Overall (N=4441)
P value<200 (N=1399)
201-350 (N=896)
351-500 (N=868)
>500 (N=1025)
Subtype, n (%)
B 2759 (62.5) 880 (62.9) 564 (61.3) 565 (64) 750 (62) 0.903
CRF02_AG 385 (8.7) 102 (7.3) 90 (9.8) 86 (9.7) 107 (8.9) 0.153
F 280 (6.3) 90 (6.4) 66 (7.2) 51 (5.8) 73 (6) 0.478
C 238 (5.4) 80 (5.7) 47 (5.1) 47 (5.3) 64 (5.3) 0.671
Other 749 (17) 247 (17.7) 153 (16.6) 134 (15.2) 215 (17.8) 0.841
Pre-cART viremia, copies/mL, n (%)
<100,000 2407 (54.6) 396 (28.3) 545 (59.2) 589 (66.7) 877 (72.5) <0.001
100,000-500,000 1242 (28.2) 550 (39.3) 270 (29.3) 213 (24.1) 209 (17.3) <0.001
500,000-1,000,000 351 (8) 227 (16.2) 49 (5.3) 38 (4.3) 37 (3.1) <0.001
>1,000,000 411 (9.3) 226 (16.2) 56 (6.1) 43 (4.9) 86 (7.1) <0.001
Armenia & Santoro, unpublished data, 2019
According to CD4 levels, no difference are observed among subtypes. The proportion of patients with pre-cART viral load >100,000 copies/mL decreases at increasing CD4 count levels.
The success of antiretroviral therapy allowed to a consequent (and dramatic) decrease of resistance development (at least in high income countries)
Beyond 2010, prevalence of resistance remains stable at around 40% from 2011 to 2018. In particular, the proportion of isolates
with at least three class-resistance remained constantly settled at around 5%.
Armenia et al., manuscript submitted
Analysis performed on 13663 isolates from 6739 ART-experienced HIV-1 infected patients, for whom GRTs for PR/RT (N=13663) and IN (N=2257) were performed for routine clinical purposes. P-values were calculated by Chi-squared test for trend; statistically significant tests (p<0.05) are indicated in boldface. Sequences performed from 1999 to 2001 were grouped.
Overall among 1247 isolates from patients under DRV treatment the prevalence of strains susceptible to DRV was 80%.
80%
9%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
P<0.001
P<0.001
P<0.001
P=0.072
P=0.346 P=0.138
Analysis performed on 1247 plasma isolates from 795 HIV-1 infected patients failing a darunavir containing regimen. P-values were calculated by Chi-squared test for trend; statistically significant tests (p<0.05) are indicated in boldface.
Santoro, Armenia et al 2019. Unpublished data
Over time this proportion increased from 30% in 2007 to 86% in 2011 in conjunction with a dramatic decrease of isolates with consistent resistance (with ≥ 3 DRV resistance mutations) from 39% in 2007 to 7% in 2011.
80%
9%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
P<0.001
P<0.001
P<0.001
P=0.072
P=0.346 P=0.138
The proportion of isolates fully susceptible to DRV continued to slightly increase from 2012 to 2018
80%
9%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
P<0.001
P<0.001
P<0.001
P=0.072
P=0.346 P=0.138
Analysis performed on 1247plasma isolates from 795 HIV-1 infected patients failing a darunavir containing regimen. P-values were calculated by Chi-squared test for trend; statistically significant tests (p<0.05) are indicated in boldface.
0% 5%
10% 15% 20% 25% 30% 35% 40% 45% 50% 55% 60% V11I
V32I L33F I47V I50V I54L I54M T74P L76V I84V L89V
Concerning the specific DRV RAMs, the prevalence of all 11 mutations dramatically decreased from 2007 to 2011. After 2010 prevalence of the DRV RAMs remained stable. I47V, I50V, I54M and T74P were no longer detected in 2018.
2007 → 2011 P value 2012 → 2018 P value
7.7% → 3.2% 0.118 3.2% → 2.7% 0.987 30.8% → 7.4% <0.001 7.4% → 4.1% 0.193 41.5% → 11.6% <0.001 11.6% → 5.5% 0.115 23.1% → 3.2% <0.001 3.2% → 0.0% 0.123 13.8% → 0.0% <0.001 0.0% → 0.0% 0.772 20.0% → 5.3% <0.001 5.3% → 4.1% 0.512 9.2% → 2.1% <0.001 2.1% → 0.0% 0.029
12.3% → 1.1% 0.001 1.1% → 0.0% 0.281 9.2% → 1.1% 0.007 1.1% → 2.7% 0.841
26.2% → 6.3% <0.001 6.3% → 4.1% 0.536 27.7% → 4.2% <0.001 4.2% → 4.1% 0.854
Seq ID Drug(s) with DRV at first-line
Pre cART viremia
PI major NRTI NNRTI
34650 FTC+TDF 634,929 40 CRF01_AE None M41ML, K219KR None
36928 FTC+TDF 1,519,820 25 CRF02_AG M46ML None None
38990 FTC+TDF >10,000,000 210 A1 None K70KT, M184MV None
41341 FTC+TDF 4,830,677 14 CRF02_AG None M184MV None
41457 FTC+TDF 4,753 178 CRF02_AG None K65R None
41596 FTC+TDF 227,276 41 CRF02_AG None M184I V179E
41615 3TC+ABC 46,964 221 G None M184MI None
Among 87 isolates from patients failing a first-line DRV-containing regimen, only 8 showed emergence of resistance. Most of these patients were in viro- immunological compromised conditions before therapy start.
0 10 20 30 40 50 60 70 80 90
100
Prevalence of resistance in clinical practice dramatically decreased over time in patients who failed a first-line
regimen
Analysis performed on 1051 sequences of protease/reverse transcriptase and 207 Integrase sequences performed for routine clinical practice in HIV-1 infected patients failing their first-line treatment (N=1041). *Integrase sequences were retrieved from 2008 from 204/1041 patients (denominators are not shown). P-values were calculated by Chi-squared test for trend; statistically significant tests (p<0.05) are indicated in boldface. Sequences performed from 1999 to 2001 were grouped.
Prevalence of resistance to PIs, NRTIs, NNRTIs and INIs (major resistance mutations from IAS/Stanford resistance lists 2017) among ART- experienced HIV-1 infected patients who failed first line treatment over the years.
P<0.001 P<0.001
P=0.584 P=0.311
Naive Advance AIDS Presenter
Boyd MA et al. HIV Medicine (2019)
HIV Diagnosis • Disclosure • HIV education • Counselling • Referral • Scheduling
1st Clinic Visit • Registered • Insurance • Assess housing,
substance use, mental health needs
• HIV education • Counselling • Labs
• Medical evaluation • Assess preparedness
ART Management • VL monitoring • Adherence • Retention
RAPID Visit: ART Start • Disclosure, counselling • Registration, Insurance • Assess housing, substance use, mental
health needs • Labs • HIV education • Counselling • Medical evaluation • Assess preparedness • ART dispensed • Telephone follow-up
Primary Care Provider Visits: ART Management
• Viral load monitoring • ART management • Adherence • Retention
Standard care based on universal ART guidelines
RAPID program
Fig. 2 Standard care based on universal ART guidelines (upper panels) vs. RAPID program same-day ART initiation (lower panels), in people newly diagnosed with HIV infection. In RAPID, the first encounter between the person and their HIV care giver provides comprehensive ART management, often on the day of diagnosis. In standard care, ART is only initiated after three encounters. Reproduced with permission [9].
DIAMOND Study
Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Rapid Initiation for HIV-1 Infection: Primary Analysis of the DIAMOND Study (POSTER PRESENTED AT THE 13 TH ANNUAL AMERICAN CONFERENCE FOR THE TREATMENT OF HIV ( ACTHIV) 2019 ; MIAMI,FLORIDA) G D. Huhn et al.
DIAMOND Week 24: Genotype at Screening/Baseline
≥1 RAM, n (%) D/C/F/TAF (n=102)a
Primary PIb 5 (5) Secondary PI 100 (98) Darunavir 0 Emtricitabine
M184M/I M184M/V
NNRTIc
T97T/A T97A
5 (5) 3 (3) 2 (2)
aGenotypes were not available for 7 patients due to being unable to amplify (ie, low viral load, reduced viral fitness, compromised sample collection/handling, primer incompatibility); bThree patients had L90M, 1 patient had M46L, and 1 patient had Q58E; RAM, resistance-associated mutation; cIndividual NNRTI RAMs are only shown for those occurring in ≥10% of patients. PI, protease inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; INI, integrase inhibitor.
33
D/C/F/TAF virologic efficacy in a rapid initiation model of care
DIAMOND Study Virologic response at Week 48
Gregory D. Huhnet al. A C T H I V 2019
Is the use of boosted DRV with DTG successful in highly treatment-
experienced individuals?
34
Beyond 2010, prevalence of resistance remains stable at around 40% from 2011 to 2018. In particular, the proportion of isolates
with at least three class-resistance remained constantly settled at around 5%.
Armenia et al., manuscript submitted
Analysis performed on 13663 isolates from 6739 ART-experienced HIV-1 infected patients, for whom GRTs for PR/RT (N=13663) and IN (N=2257) were performed for routine clinical purposes. P-values were calculated by Chi-squared test for trend; statistically significant tests (p<0.05) are indicated in boldface. Sequences performed from 1999 to 2001 were grouped.
Durability of dolutegravir plus boosted darunavir as salvage or simplification of salvage regimens in HIV-1 infected, highly treatment-experienced subjects.
Capetti AF, De Socio GV, Cossu MV, Sterrantino G, Cenderello G, Cattelan A, Baldin GM, Soria A, Riccardi N, Niero FP, Celesia BM, Barbarini G, Rusconi S, Rizzardini G.
BACKGROUND: Dolutegravir (DTG) plus boosted darunavir (bDRV) is a compact, adherence- friendly salvage regimen with the highest genetic barrier to HIV-1 resistance. OBJECTIVE: Aim of the present study is to assess the long term (96-week) safety and efficacy of DTG + bDRV in a of multidrug-experienced HIV-1 infected patients, simplifying or building rescue regimens. METHODS: All HIV-1-infected subjects from eleven Italian centers switched to DTG + bDRV between March 2014 and September 2015 were included and followed for minimum 96 weeks. RESULTS: The cohort comprises 130 subjects, switched from 42 different, complex or at least twice-daily regimens, mainly for simplification (44.6%), viral failure (30.0%) or toxicity (16.6%). At baseline 118 had documented resistance to 1-5 antiretroviral classes and 12 lacked genotypic results either for historical reasons or for problems with primer annealing; 52 (40%) had uncontrolled viral replication, three above 500.000 copies/mL. At week 96 two showed ≥50 HIV-1 RNA copies/mL, 23 had 1-49 copies/mL and 101 had no virus detected. The proportion of subjects presenting abnormal values at baseline significantly decreased for serum glucose, creatinine, AST, total cholesterol and triglycerides. CONCLUSIONS: These long-term data confirm the reliability of the two-drug regimen consisting of bDRV plus DTG in salvage settings in HIV-1 infection.
HIV Clin Trials 2018
37
BACKGROUND: The use of dual antiretroviral therapy (ART) regimens for treatment of HIV is increasing. The contemporary combination of boosted darunavir with dolutegravir has not been widely studied. METHODS: This was a retrospective cohort study that evaluated treatment-experienced individuals within three large urban clinics prescribed boosted darunavir with dolutegravir (study regimen) dual therapy. Follow-up was defined as the number of days from regimen initiation until the last HIV- RNA determination on the study regimen. Virologic outcomes, HIV-RNA ≤50 copies/ml (undetectable), were assessed overall and by baseline HIV-RNA status. RESULTS: Of 65 individuals included, 83% were at least 3-class antiretroviral experienced and median time since starting ART was 19 years (IQR 13-22). Median follow-up was 419 days (IQR 286-744). An undetectable HIV-RNA was achieved by 62/65 (95%) individuals at any time point on the study regimen. At the end of follow-up 61/65 (94%) individuals remained undetectable, including 48/49 (98%) with an undetectable HIV-RNA at baseline (those changing for optimization) and 13/16 (81%) with viremia at baseline (those changing therapy during virologic failure). At the end of follow-up, 55 (85%) individuals were still taking the study regimen. No individuals stopped therapy due to virologic failure or intolerance. CONCLUSIONS: In a highly treatment experienced cohort, boosted darunavir with dolutegravir dual therapy demonstrated high rates of virologic success, even in those with detectable HIV- RNA prior to initiating the study regimen. Further study of this potent, simple, high-barrier dual- class regimen is warranted.
Boosted darunavir and dolutegravir dual therapy among a cohort of highly treatment-experienced individuals. Hawkins KL, Montague BT, Rowan SE, Beum R, McLees MP, Johnson S, Gardner EM.
Antivir ther Sep 2019
Conclusions • Today >90% of patients starting a first-line cART regimen
achieve virological suppression, yet, virological rebound remains a concern!! Thus, we should care in order to maintain virological success. • Genetic barrier represent a key tool to help in the long-term
control of viral replication and related damage
• For the long-term maintenance of success, viremia, CD4 cell count and resistance are still fundamental parameters to be considered to avoid failure and the re-emergence of archived resistance in the case of treatment switch.
• A personalized approach to single patient needs is still (and today more than in the past) a key factor to warrant the best virological and clinical result
Thank you for the attention!
Diapositiva numero 1
Major results of pivotal studies with STR- TAF/FTC vs DTG -3TC based in drug-naive HIV patients
The achievement of virological success is also influenced by the levels of CD4 cell count pre-cART!
The evaluation of CD4 cell count before therapy start is still today crucial, since >30% of newly diagnosed individuals has CD4 cell count <200 cells/mm3
DIAMOND Study
DIAMOND Week 24: Genotype at Screening/Baseline
D/C/F/TAF virologic efficacy in a rapid initiation model of care DIAMOND Study Virologic response at Week 48
Is the use of boosted DRV with DTG successful in highly treatment-experienced individuals?

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ART oggi: strategie in evoluzione ed innovazione