scholarly journals 2486. Clinical Outcomes of Patients Treated with Dolutegravir Functional Monotherapy or Dolutegravir plus an Active Non-cytosine Nucleoside Analog: A Retrospective Observational Cohort Study of Treatment-Experienced Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S861-S862
Author(s):  
Charlotte-Paige M Rolle ◽  
Beth Bryant ◽  
Colton J Tucker ◽  
Maria Camila Castro ◽  
Vu Nguyen ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Real World ◽  
Virologic Failure ◽  
Subsequent Development ◽  
Nucleoside Analog ◽  
Cd4 Count ◽  
Virologic Suppression ◽  
Count Range ◽  
Virologic Control ◽  
Hiv 1

Abstract Background Dual dolutegravir (DTG)-containing regimens (DCRs) are currently approved for the treatment of antiretroviral (ARV) naïve and experienced patients with HIV-1 infection. DTG monotherapy has resulted in unacceptable rates of virologic failure and subsequent development of DTG resistance. Here, we evaluate the “real-world” efficacy and “barrier to resistance” of DCRs containing 0–1 active ARVs. Methods This is a retrospective observational study evaluating clinical outcomes of treatment-experienced patients on combination DCRs found to be on DTG functional monotherapy or DTG plus an active non-cytosine analog between 2013 and 2014. The primary endpoint was virologic suppression (HIV-1 RNA< 50 copies/mL) at week 48. Virologic failure (VF) was defined as confirmed HIV-1 RNA≥ 50 copies/mL 12 weeks after initiating DTG or any time after achieving HIV-1 RNA< 50 copies/mL. Adherence, adverse events (AEs) and laboratory parameters were analyzed throughout the study. Results Thirty-nine patients were included in the analysis, 19 (49%) were on DTG functional monotherapy and 20 (51%) were on DTG plus a non-cytosine nucleoside analog. The median age (range) was 53 (40–74) years, median baseline CD4+ count (range) was 564 (92–1217) cells/mm3, 22 (56%) had baseline HIV-1 RNA< 50 copies/mL, and 24 (62%) had previously used INSTIs (Table 1). At Weeks 48 and 96, virologic suppression was observed in 78.3% and 86% of patients respectively (Figures 1 and 2). Among 7 VFs (2 on DTG functional monotherapy, 5 on DTG plus a non-cytosine nucleoside analog), there was no evidence of treatment-emergent resistance to DTG. There was a significant median increase in CD4+ count from baseline to Week 48 (+90 cells/mm3, 95% confidence interval: [14.18, 165.9]). No significant changes in lipid parameters were observed. Treatment-related AEs occurred in 17/39 (44%) patients (all Grade 1–2) and 1 patient discontinued DCR treatment due to rash. Conclusion In this “real-world” cohort of treatment-experienced patients, we observed that DTG functional monotherapy and DTG plus a non-cytosine nucleoside analog maintained long-term virologic control and was well tolerated. These data supports use of DTG as a partner for dual DCRs given its high efficacy in patients with underlying ARV resistance. Disclosures All authors: No reported disclosures.

scholarly journals Virologic Outcomes of Switching to Dolutegravir Functional Monotherapy, or Functional Dual Therapy With Dolutegravir Plus A Non-cytosine Nucleoside Analog: A Retrospective Study of Treatment-Experienced, HIV-1 Infected Patients

2020 ◽  
Author(s):  
Charlotte-Paige Rolle ◽  
Vu Nguyen ◽  
Federico Hinestrosa ◽  
Edwin DeJesus
Keyword(s):  
Retrospective Study ◽  
Observational Study ◽  
Median Duration ◽  
Primary Endpoint ◽  
Real World ◽  
Virologic Failure ◽  
Dual Therapy ◽  
Nucleoside Analog ◽  
Hiv 1

Abstract Background Dolutegravir (DTG) monotherapy results in unacceptable virologic failure rates and the development of DTG resistance. Here, we evaluated virologic outcomes of patients switched to DTG functional monotherapy, or functional dual therapy with DTG plus a non-cytosine nucleoside analog (NA).Methods This observational study included treatment-experienced patients switched to regimens containing ≥ 3 antiretrovirals later found to be on DTG functional monotherapy, or functional dual therapy with DTG plus a non-cytosine NA based on historical genotypes. Eligible patients were either suppressed or viremic at baseline and had ≥2 HIV-1 RNA measurements at least four weeks apart following switch. The primary endpoint was the proportion with HIV-1 RNA<50 copies/mL following switch. Results Thirty-nine patients were included, 19 (49%) were found to be on DTG functional monotherapy and 20 (51%) were found to be on functional dual therapy with DTG plus a non-cytosine NA. The median duration of follow-up was 50 weeks (range 12-244). Following switch, 32/39 (82%) patients achieved or maintained an HIV-1 RNA<50 copies/mL. In 7 (18%) patients with persistent HIV-1 RNA ≥50 copies/mL, there was no evidence of treatment-emergent resistance among those with post-switch genotypes.Conclusions In this real-world cohort, the majority of whom had virus with the M184V/I and ≥ 1 additional NA mutation, switching to DTG functional monotherapy, or functional dual therapy with DTG plus a non-cytosine NA resulted in persistent HIV-1 RNA≥ 50 copies/mL in 18%. None with post-switch genotypes developed treatment-emergent resistance.

scholarly journals 2482. Clinical Outcomes of Once-Daily Darunavir in Treatment-Experienced Patients with Darunavir Resistance Associated Mutations Through 48 Weeks of Treatment

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S859-S860
Author(s):  
Charlotte-Paige M Rolle ◽  
Omar Marquez ◽  
Vu Nguyen ◽  
Federico Hinestrosa ◽  
Edwin DeJesus
Keyword(s):  
Clinical Outcomes ◽  
Treatment Guidelines ◽  
Patient Adherence ◽  
Cd4 Count ◽  
Lipid Lowering ◽  
Virologic Suppression ◽  
Lipid Lowering Therapy ◽  
Number Range ◽  
Once Daily ◽  
Hiv 1

Abstract Background Darunavir (DRV) is a well-tolerated, potent protease inhibitor used once-daily in patients with no DRV resistance-associated mutations (RAMs) and twice-daily in those with DRV RAMs. Treatment guidelines encourage use of once-daily regimens to optimize patient adherence, convenience and tolerability. Several studies suggest that once-daily DRV retains efficacy in the setting of 1–2 DRV RAMs whereas 3 or more DRV RAMs (with multiple background PI RAMs) is needed for DRV resistance. Currently, there is little clinical data to support the long-term use of once-daily DRV in patients with DRV RAMs. Methods This is a retrospective study evaluating the 48-week clinical outcomes of 22 treatment-experienced patients with DRV RAMs switched to once-daily DRV between 2014 and 2017 at the Orlando Immunology Center. The primary endpoint was the proportion with virologic suppression (HIV-1 RNA< 50 copies/mL) at Week 48. Adherence, adverse events (AEs) and laboratory parameters were analyzed throughout the study. Results The median age (range) of the sample was 53 (21–77) years, median baseline CD4+ count was 609 cells/mm3, 18 (82%) had baseline HIV-1 RNA <50 copies/mL, 15 (69%) had previously used 1 or more PIs and median number (range) of baseline DRV RAMs was 2 (1–5) (Table 1). At Week 48, 20 (91%) had HIV-1 RNA <50 copies/mL; 2 (9%) virologic non-responders had HIV-1 RNA of 82 and 59,637 copies/mL and reported noncompliance (Figure 1). There was no significant change in median CD4+ count from baseline to Week 48 (+22, 95% confidence interval (CI): [−116.5; 56.0]). Once-daily DRV was associated with a significant median increase in HDL cholesterol (+82, 95% CI: [37.0; 101.0]) and a significant median decrease in LDL cholesterol (-60, 95% CI: [-89.5; -31.0]). There were no significant changes in the proportion of patients on lipid lowering therapy at baseline and week 48 (p = 0.33). There were no self-reported AEs or Grade 3–4 lab abnormalities through Week 48. Conclusion Once-daily DRV maintained virologic control in this cohort of treatment-experienced patients with 1 or more baseline DRV RAMs and was safe and well-tolerated. This suggests that once-daily DRV may be effective in this population however further data are needed to validate this as a viable treatment option. Disclosures All authors: No reported disclosures.

scholarly journals Long-term Outcomes in a Large Randomized Trial of HIV-1 Salvage Therapy: 96-Week Results of AIDS Clinical Trials Group A5241 (OPTIONS)

2019 ◽  
Vol 221 (9) ◽  
pp. 1407-1415 ◽  
Author(s):  
Rajesh T Gandhi ◽  
Karen T Tashima ◽  
Laura M Smeaton ◽  
Vincent Vu ◽  
Justin Ritz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Salvage Therapy ◽  
Virologic Failure ◽  
Virologic Suppression ◽  
Cumulative Activity ◽  
Antiretroviral Medications ◽  
Resistant Group ◽  
Aids Clinical Trials ◽  
Hiv 1

Abstract Background Short-term (48-week) results of the OPTIONS trial showed that nucleoside reverse transcriptase inhibitors (NRTIs) can be safely omitted from salvage therapy as long as the regimen has a cumulative activity of &gt;2 active antiretroviral medications. The long-term durability of this approach and outcomes in persons who have more-extensive HIV-1 drug resistance are uncertain. Methods Participants with virologic failure and anticipated antiretroviral susceptibility received an optimized regimen and were randomized to omit or add NRTIs. A separate group with more resistance (cumulative activity ≤2 active agents) received an optimized regimen including NRTIs. Results At week 96, among 360 participants randomized to omit or add NRTIs, 70% and 65% had HIV-1 RNA &lt;200 copies/mL, respectively. Virologic failure was uncommon after week 48. Younger age and starting fewer new antiretroviral medications were associated with higher odds of virologic failure. In the highly resistant group, 53% had HIV-1 RNA &lt;200 copies/mL at week 96. Conclusions HIV-1 salvage therapy can safely omit NRTIs without compromising efficacy or durability of response as long as the new regimen has a cumulative activity of &gt;2 active drugs. Younger people and those receiving fewer new antiretrovirals require careful monitoring. Even among individuals with more-extensive resistance, most achieve virologic suppression. Clinical Trials Registration NCT00537394.

scholarly journals 833. Efficacy and Safety of Long-Acting Cabotegravir + Rilpivirine in Participants with HIV/HCV Co-infection: ATLAS-2M 48-Week Results

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S508-S509
Author(s):  
Ronald D’Amico ◽  
Paul Benn ◽  
Shanker Thiagarajah ◽  
Susan L Ford ◽  
Eileen Birmingham ◽  
...  
Keyword(s):  
Research And Development ◽  
Injection Site ◽  
Virologic Failure ◽  
Hcv Rna ◽  
Virologic Suppression ◽  
Efficacy And Safety ◽  
Modes Of Transmission ◽  
Long Acting ◽  
Chronic Hcv ◽  
Hiv 1

Abstract Background The phase IIIb ATLAS-2M study demonstrated non-inferiority of long-acting (LA) cabotegravir (CAB) + rilpivirine (RPV) dosed every 8 weeks (Q8W) compared with every 4 weeks (Q4W) for maintenance of virologic suppression. Hepatitis C virus (HCV) co-infection occurs in ~6% of people with HIV due to shared modes of transmission. We report efficacy and safety of CAB + RPV LA in participants with HIV/HCV co-infection in ATLAS-2M. Methods Participants with HIV-1 RNA &lt; 50 c/mL receiving CAB + RPV LA Q4W (transitioned from ATLAS [NCT02951052]) or oral comparator ART were randomized 1:1 to receive CAB + RPV LA Q4W or Q8W. Baseline HCV RNA was assessed by polymerase chain reaction. Participants with symptomatic chronic HCV infection requiring treatment within 12 months or liver enzymes not meeting entry criteria were excluded. Week 48 assessments included proportion with HIV-1 RNA ≥50 and &lt; 50 c/mL (Snapshot algorithm), general and hepatic safety, and pharmacokinetics. Results HIV/HCV co-infection was present in 10 (1%) of 1045 participants, 60% of whom were female at birth. At Week 48, 9/10 (90%) and 972/1035 (94%) participants with HIV/HCV co-infection and HIV mono-infection, respectively, had HIV-1 RNA &lt; 50 c/mL (adjusted difference, 4.1; 95% CI, −14.5 to 22.6). No participants with HIV/HCV co-infection had HIV-1 RNA ≥50 c/mL (vs 14/1035 [1%] with HIV mono-infection) or confirmed virologic failure through Week 48 (vs 10 [1%] with HIV mono-infection); 1/10 (10%) discontinued for reasons other than adverse events (AEs). Excluding injection site reactions (ISRs), AEs and serious AEs were reported in 4 (40%) and 0 participants with HIV/HCV co-infection, respectively; the only AE reported in &gt;1 participant was injection site pain (n=5; 50%). In participants with HIV/HCV co-infection, all ISRs were grade 1/2; none led to withdrawal. No hepatic laboratory abnormalities were reported in participants with HIV/HCV co-infection through Week 48; rates were low in those with HIV mono-infection (Table). Plasma CAB and RPV concentrations were similar between groups. Conclusion CAB + RPV LA was effective and well tolerated in this small cohort of participants with HIV and asymptomatic HCV co-infection. Disclosures Ronald D’Amico, DO, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Paul Benn, MB ChB FRCP, ViiV Healthcare (Employee) Shanker Thiagarajah, MB ChB, GlaxoSmithKline (Employee, Shareholder) Susan L. Ford, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Eileen Birmingham, MD, MPH, Janssen Research and Development (Employee, Shareholder) Ojesh R. Upadhyay, MPH, MBA, GlaxoSmithKline (Employee) Louise Garside, PhD, GlaxoSmithKline (Employee) Rodica Van Solingen-Ristea, MD, Janssen Research and Development (Employee)ViiV Healthcare (Employee) Kati Vandermeulen, M.SC., Janssen Research and Development (Employee) William Spreen, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

scholarly journals 877. North American Phase 3/3b Experience with Long-Acting Cabotegravir and Rilpivirine: Efficacy, Safety, and Virologic Outcomes

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S530-S531
Author(s):  
Babafemi O Taiwo ◽  
Darrell Tan ◽  
Parul Patel ◽  
Paula Teichner ◽  
Joseph Polli ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
Virologic Failure ◽  
Descriptive Analysis ◽  
Injection Site Reaction ◽  
Treatment Preference ◽  
Virologic Suppression ◽  
Research Support ◽  
Phase 3 ◽  
Long Acting ◽  
Hiv 1

Abstract Background Cabotegravir (CAB) plus rilpivirine (RPV) is the first complete long-acting (LA) regimen recommended by treatment guidelines for the maintenance of HIV-1 virologic suppression. CAB+RPV LA dosed every 4 weeks (Q4W) or every 8 weeks (Q8W) demonstrated noninferior efficacy in multinational Phase 3/3b trials. This post hoc descriptive analysis summarizes efficacy, virologic outcomes, safety, and treatment preference for US and Canadian (CAN) participants through Week (W) 48. Methods This analysis focuses on data for US/CAN participants naive to CAB+RPV (n=376) from the larger pooled population of the ATLAS, FLAIR, and ATLAS-2M Phase 3/3b studies (N=1245). Endpoints included the proportion of participants with plasma HIV-1 RNA ≥ 50 and &lt; 50 c/mL at W48 (FDA Snapshot algorithm), incidence of confirmed virologic failure (CVF; 2 consecutive HIV-1 RNA ≥ 200 c/mL), safety, and treatment preference through W48. Results 376 US/CAN participants received CAB+RPV LA Q4W or Q8W. Median (range) age was 39y (20–74); 14.9% were female, 66.0% were White. At W48, 93.1% (350/376) maintained virologic suppression (HIV-1 RNA &lt; 50 c/mL), 1.9% (7/376) had HIV-1 RNA ≥ 50 c/mL, and 0.8% (3/376) met the CVF criterion, consistent with the overall global pooled population (Table 1). Two of the three participants with CVF had ≥ 2 of the three baseline factors (archived RPV resistance-associated mutations [RAMs], HIV subtype A6/A1, body mass index [BMI] ≥ 30 kg/m2) previously associated with CVF. Among the US/CAN participants with a single baseline factor, none met CVF. Overall, archived RPV RAMs were observed in 3.2% (12/376), HIV subtype A6/A1 in 1.1% (4/376), and BMI ≥ 30 kg/m2 in 26.3% (99/376) of participants. Safety and injection site reaction findings were similar to the overall pooled population (Table 2). Most participants (120/134, 89.6%) preferred LA over oral dosing (7/134, 5.2%). Table 1. Snapshot outcomes following CAB+RPV LA Q4W and Q8W at Week 48 in participants naive to CAB+RPV from ATLAS, FLAIR, and ATLAS-2M (ITT-E population) Table 2. Safety summary through Week 48 following CAB+RPV LA Q4W and Q8W or comparator ART in participants naive to CAB+RPV from ATLAS, FLAIR, and ATLAS-2M Conclusion In US/CAN Phase 3/3b trial participants, CAB+RPV LA was highly effective and well tolerated, with outcomes consistent with the overall pooled population. Baseline prevalence of archived RPV RAMs and subtype A6/A1 was low and aligned with regional prevalence/surveillance data. CAB+RPV LA provides a tolerable and effective injectable LA treatment option for virologically suppressed US/CAN individuals with HIV. Disclosures Babafemi O. Taiwo, MBBS, Gilead (Consultant)Merck (Consultant)ViiV Healthcare (Consultant) Darrell Tan, MD PhD, Abbvie (Grant/Research Support)Gilead (Grant/Research Support)GlaxoSmithKline (Scientific Research Study Investigator)ViiV Healthcare (Grant/Research Support) Parul Patel, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Paula Teichner, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Joseph Polli, PhD, FAAPS, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Louise Garside, PhD, GlaxoSmithKline (Employee) Ronald D’Amico, DO, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Christine L. Talarico, M.S., GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Rodica Van Solingen-Ristea, MD, Janssen Research and Development (Employee)ViiV Healthcare (Employee) Bryan Baugh, MD, Janssen, Johnson & Johnson (Employee, Shareholder) William Spreen, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Michael Aboud, MBChB, MRCP, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Matthew Bosse, DO, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

Antiretroviral Therapy in Pregnant Women

2017 ◽  
Author(s):  
William R. Short ◽  
Jason J. Schafer
Keyword(s):  
Pregnant Women ◽  
Antiretroviral Drugs ◽  
Virologic Suppression ◽  
Mother To Child Transmission ◽  
Child Transmission ◽  
Virologic Control ◽  
Treatment Changes ◽  
Mother To Child ◽  
Hiv 1 ◽  
Pregnancy Registry

Research has demonstrated that proper prevention strategies and interventions during pregnancy, labor, and delivery can significantly reduce the rate of mother-to-child transmission of HIV. Antiretroviral drugs (ARVs) should be initiated in all HIV-infected pregnant women regardless of CD4+ T cell count or HIV-1 RNA level. ARVs should be given in combination therapy, similar to nonpregnant patients, with the goal of complete virologic suppression. Treatment changes during pregnancy have been associated with the loss of virologic control and independently associated with mother-to-child transmission. All cases of prenatal antiretroviral exposure should be reported to the Antiretroviral Pregnancy Registry, which collects data on HIV-infected pregnant women taking ARVs with the goal of detecting any major teratogenic effects.

scholarly journals 2494. Real-World Use of Ibalizumab in Physician Office Infusion Centers (POICs)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S865-S865 ◽  
Author(s):  
Richard C Prokesch ◽  
Claudia P Schroeder ◽  
Thomas C Hardin ◽  
Lucinda J Van Anglen
Keyword(s):  
Clinical Trial ◽  
Viral Load ◽  
Adverse Events ◽  
Real World ◽  
Clinical Trial Data ◽  
Cd4 Count ◽  
Drug Classes ◽  
Post Marketing ◽  
Marketing Data ◽  
Hiv 1

Abstract Background Ibalizumab-uiyk (IBA) was recently approved for the treatment of multi-drug-resistant HIV-1 infection in patients (pts) failing other antiretroviral regimens. Clinical trial data demonstrated a decrease in HIV-1 viral load in 83% and 43% of patients (n = 40) receiving IBA for 2 and 25 weeks (weeks), respectively. Real-world post marketing data are needed. This pilot study reports the experience of IBA utilization in POICs. Methods Medical records of patients receiving intravenous IBA from approval through April 2019 were reviewed. Data collected include demographics, infection and treatment history, IBA regimen and adverse events. Plasma HIV-1 RNA viral load (log10 copies/mL) and CD4 count (cells/µL) were collected at baseline and as available during therapy. Based on available follow-up (FU) labs, response was assessed at 4–10 weeks (FU 1), 14–22 weeks (FU 2), and 24–37 weeks (FU 3). Results Nine patients (mean age: 48 ± 11 years, 67% male) from 7 POICs received IBA for a median duration of 33 weeks (range 4–43). Median length of HIV-1 diagnosis was 22 years (range 8–25). Resistance to ≥1 drug in at least 3 drug classes was reported in 56%. All patients received at least one concurrent anti-retroviral agent. IBA was initiated at 2000 mg followed by 800 mg every 2 weeks. All patients received infusions as scheduled (151 total infusions) except for one requiring a second loading dose. Baseline mean CD4 count and viral load were 49 cells/µL and 4.9 log10 copies/mL, respectively. Labs obtained at FU 1 indicated a decrease in viral load of at least 0.5 log10 copies/mL in 6/8 patients (75%); a mean reduction of 2.1 ± 1.8 log10 copies/mL (Table 1). Mean HIV-1 titers available for patients at FU 2 (n = 6) and FU 3 (n = 7) were 3.1 ± 2.0 and 3.2 ± 2.6 log10 copies/mL, respectively. Mean CD4 counts were 65 ± 57 cells/µL at FU 1, 96 ± 61 cells/µL at FU 2 and 88 ± 82 cells/µL at FU 3. Adverse events were reported in 8 patients (89%), most common itching/rash, diarrhea and abdominal pain. None resulted in discontinuation of IBA. Conclusion This study confirms the antiviral activity of IBA in patients with advanced HIV-1 infection in the real-world setting. We observed well-tolerated therapy with an early reduction in HIV-1 viral load of 75%, followed by a 43% reduction ≥24 weeks, consistent with the clinical trial. Disclosures All authors: No reported disclosures.

scholarly journals Virological Failure and Acquired Genotypic Resistance Associated With Contemporary Antiretroviral Treatment Regimens

2020 ◽  
Vol 7 (9) ◽  
Author(s):  
Soo-Yon Rhee ◽  
Dana Clutter ◽  
C Bradley Hare ◽  
Christophe T Tchakoute ◽  
Kristin Sainani ◽  
...  
Keyword(s):  
Virologic Failure ◽  
Virus Transmission ◽  
Cd4 Count ◽  
Virologic Suppression ◽  
Strand Transfer ◽  
Genotypic Resistance ◽  
Acquired Drug Resistance ◽  
Virus Load ◽  
Treatment Regimens ◽  
Art Initiation

Abstract Background There are few descriptions of virologic failure (VF) and acquired drug resistance (HIVDR) in large cohorts initiating contemporary antiretroviral therapy (ART). Methods We studied all persons with HIV (PWH) in a California clinic population initiating ART between 2010 and 2017. VF was defined as not attaining virologic suppression, discontinuing ART, or virologic rebound prompting change in ART. Results During the study, 2315 PWH began ART. Six companion drugs were used in 93.3% of regimens: efavirenz, elvitegravir/c, dolutegravir, b-darunavir, rilpivirine, and raltegravir. During a median follow-up of 36 months, 214 (9.2%) PWH experienced VF (2.8 per 100 person-years) and 62 (2.7%) experienced HIVDR (0.8 per 100 person-years). In multivariable analyses, younger age, lower CD4 count, higher virus load, and b-atazanavir were associated with increased VF risk; lower CD4 count, higher virus load, and nevirapine were associated with increased HIVDR risk. Compared with efavirenz, dolutegravir, raltegravir, and b-darunavir were associated with reduced HIVDR risk. Risks of VF and HIVDR were not significantly associated with ART initiation year. Of the 62 PWH with HIVDR, 42 received an non-nucleoside RT inhibitor (NNRTI), 15 an integrase-strand transfer inhibitor (INSTI), and 5 a protease inhibitor (PI). Among those with HIVDR on an NNRTI or first-generation INSTI, 59% acquired dual class resistance and 29% developed tenofovir resistance; those receiving a PI or dolutegravir developed just M184V. Conclusions Despite the frequent use of contemporary ART regimens, VF and HIVDR continue to occur. Further efforts are required to improve long-term ART virological responses to prevent the consequences of ongoing HIV-1 replication including virus transmission and HIVDR.

scholarly journals Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring

2018 ◽  
Vol 69 (3) ◽  
pp. 523-529 ◽  
Author(s):  
Sharon A Riddler ◽  
Jennifer E Balkus ◽  
Urvi M Parikh ◽  
John W Mellors ◽  
Carolyne Akello ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Disease Progression ◽  
Virologic Failure ◽  
Vaginal Ring ◽  
Phase Iii ◽  
Virologic Suppression ◽  
Cell Counts ◽  
The Impact ◽  
Hiv 1

Abstract Background A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART). Methods HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network–020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring. Results Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients (log-rank P = .40). Among the 81 participants with at least 6 months of post-ART follow-up, 19 (24%) experienced virologic failure (dapivirine: 6/32, 19%; placebo: 13/39, 27%; P = .42). Conclusions The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring. Clinical Trials Registration NCT016170096 and NCT00514098.

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