Predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine

Abstract Background Phase III/IIIb studies demonstrated cabotegravir (CAB) + rilpivirine (RPV) long-acting (LA) dosed every 4 weeks (Q4W) was noninferior to current antiviral regimen (CAR) (FLAIR and ATLAS) and CAB + RPV LA dosed every 8 weeks (Q8W) was noninferior to Q4W (ATLAS-2M) through Week 48 (W48). HIV-1 ribonucleic acid (RNA) blips (viral load [VL] ≥50 to < 200 c/mL) are common during antiretroviral therapy (ART) and generally not associated with subsequent virologic failure (2 consecutive HIV-1 RNA ≥200 c/mL). We compared the frequency of HIV-1 RNA blips and low-level qualitative and quantitative HIV-1 RNA replication among participants treated with CAB+RPV LA and oral CAR and assessed impact on virologic outcome. Methods Plasma samples collected at study visits were analyzed for HIV-1 RNA viral load using the Abbott RealTime HIV-1 assay and qualitative target detected (TD) or target not detected (TND) outcomes were provided for HIV-1 RNA < 40 c/mL. The HIV-1 SuperLow assay (bioMONTR Labs) was used to measure HIV-1 RNA < 2 c/mL at Baseline and W48. Results The proportion of participants with HIV-1 RNA blips was similar overall between Q4W CAB + RPV LA and CAR arms in FLAIR (38/283 [13%] vs 39/283 [14%]) and ATLAS (17/308 [6%] vs 23/308 [7%]). Presence of HIV-1 RNA blips in either arm was not associated with virologic non-response at W48 (HIV-1 RNA ≥50 c/mL per US Food and Drug Administration Snapshot). In ATLAS-2M, HIV-1 RNA blips were observed in 32/523 (6%; Q4W) and 18/522 (3%; Q8W) of participants, with W48 virologic nonresponse in 2 Q4W and 0 Q8W participants. TD outcomes at individual study visits were comparable between study arms for the 3 studies. At W48, the proportion of participants with HIV-1 RNA < 2 c/mL was similar to Baseline and similar between treatment groups in all studies. Conclusion The proportions of study participants with HIV-1 RNA blips, TD viral load results, and HIV-1 < 2 c/mL were similar between the Q4W and Q8W CAB+RPV LA and the oral 3-drug CAR arms through W48 in phase III/IIIb studies. HIV-1 RNA blips did not predict virologic nonresponse (Snapshot analysis) at W48. Disclosures Christine L. Talarico, M.S, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Sterling Wu, PhD, GlaxoSmithKline (Employee, Shareholder) Marty St. Clair, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Veerle Van Eygen, MSc, Janssen Pharmaceutica NV (Employee) Krischan J. Hudson, PhD, MPH, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Sandy Griffith, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Conn M. Harrington, BA, ViiV Healthcare (Employee) Jan van Lunzen, MD, PhD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) David Margolis, MD, MPH, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) William Spreen, PharmD, ViiV Healthcare (Employee, Shareholder)

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1029 ◽

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 < 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 < 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 < 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 >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)

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1072 ◽

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 < 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 < 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)

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Impact of Integrase Sequences From HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01702-21 ◽

2022 ◽

Author(s):

Jerry L. Jeffrey ◽

Marty St. Clair ◽

Ping Wang ◽

Chunfu Wang ◽

Zhufang Li ◽

...

Keyword(s):

Virologic Failure ◽

Fold Change ◽

Effective Capacity ◽

Virologic Suppression ◽

Subtype B ◽

Long Acting ◽

Breakthrough Experiments ◽

The Impact ◽

Hiv 1

The FLAIR study demonstrated noninferiority of monthly long-acting cabotegravir + rilpivirine vs daily oral dolutegravir/abacavir/lamivudine for maintaining virologic suppression. Three participants who received long-acting therapy had confirmed virologic failure (CVF) at Week 48, and all had HIV-1 that was originally classified as subtype A1 and contained the baseline integrase polymorphism L74I; updated classification algorithms reclassified all 3 as HIV-1 subtype A6. Retrospectively, the impact of L74I on in vitro sensitivity and durability of response to cabotegravir in HIV-1 subtype B and A6 backgrounds was studied. Site-directed L74I and mutations observed in participants with CVF were generated in HIV-1 subtype B and a consensus integrase derived from 3 subtype A6 CVF baseline sequences. Rilpivirine susceptibility was assessed in HIV-1 subtype B and A1 containing reverse transcriptase mutations observed in participants with CVF. HIV-1 subtype B L74I and L74I/G140R mutants and HIV-1 subtype A6 I74L and I74/G140R mutants remained susceptible to cabotegravir; L74I/Q148R double mutants exhibited reduced susceptibility in HIV-1 subtypes B and A6 (half maximal effective capacity fold change, 4.4 and 4.1, respectively). Reduced rilpivirine susceptibility was observed across HIV-1 subtypes B and A1 with resistance-associated mutations K101E or E138K (half maximal effective capacity fold change, 2.21 to 3.09). In cabotegravir breakthrough experiments, time to breakthrough was similar between L74 and I74 viruses across HIV-1 subtypes B and A6; Q148R was selected at low cabotegravir concentrations. Therefore, the L74I integrase polymorphism did not differentially impact in vitro sensitivity to cabotegravir across HIV-1 subtype B and A6 integrase genes (ClinicalTrials.gov identifier: NCT02938520).

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73. Interim Resistance Analysis of Long-Acting Lenacapavir in Treatment-Naïve People with HIV at 28 Weeks

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.073 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S48-S48

Author(s):

Laurie VanderVeen ◽

Nicolas Margot ◽

Vidula Naik ◽

Silvia Chang ◽

Ross Martin ◽

...

Keyword(s):

Virologic Failure ◽

Amino Acid Residues ◽

Resistance Analysis ◽

Treatment And Prevention ◽

Subtype B ◽

Treatment Naïve ◽

Long Acting ◽

Hiv 1 ◽

Prevention Of Hiv

Abstract Background Lenacapavir (LEN) is a first-in-class HIV-1 capsid (CA) inhibitor in clinical development for treatment and prevention of HIV-1 infection. CALIBRATE is an ongoing, phase 2 clinical study evaluating subcutaneous (SC) or oral LEN, in combination with other antiretrovirals, in treatment-naïve people with HIV-1. High rates of virologic success (HIV-1 RNA < 50 copies/mL) were achieved with LEN-based regimens by FDA Snapshot analysis at Week 28. Here, we present interim resistance analyses through Week 28. Methods Participants were randomized (2:2:2:1) to treatment groups (TG) (Figure): SC LEN + oral daily emtricitabine/tenofovir alafenamide (F/TAF); at Week 28, participants switch F/TAF to oral TAF (TG-A) or bictegravir (B, BIC) (TG-B); oral daily LEN + F/TAF (TG-C), or oral daily B/F/TAF (TG-D). Genotypic analyses (population sequencing) of HIV-1 reverse transcriptase and integrase, and genotypic (deep sequencing)/phenotypic analyses for CA were performed at screening; genotypic and phenotypic analyses were conducted at confirmed virologic failure. Figure CALIBRATE Study Design Results 182 participants were randomized and dosed in TG-A to D (n=52, 53, 52, 25). Most participants had subtype B HIV-1 (92.9%). Sequence analysis of baseline samples found 65% of amino acid residues were conserved with < 1% variation across CA overall, and 55% of residues were fully conserved. No mutations were detected at 6 positions in CA associated with reduced susceptibility to LEN in vitro; residues were fully conserved at 5 positions (L56, M66, Q67, K70, N74), and < 2% variation was observed at 1 position (T107). Three participants met the criteria for resistance analysis: 2 participants resuppressed to < 50 copies/mL while continuing treatment. One participant on SC LEN + F/TAF developed emergent resistance to LEN (Q67H+K70R) and emtricitabine (M184M/I), followed by resuppression after starting dolutegravir, zidovudine + lamivudine, tenofovir disoproxil fumarate. Conclusion Emergent resistance to LEN was uncommon in treatment-naïve participants receiving SC or oral LEN (0.6%, 1/157). These interim resistance findings support the ongoing evaluation of LEN for treatment and prevention of HIV. Disclosures Laurie VanderVeen, PhD, Gilead Sciences (Employee, Shareholder) Nicolas Margot, MA, Gilead Sciences (Employee, Shareholder) Vidula Naik, MSc, Gilead Sciences (Employee, Shareholder) Silvia Chang, Masters, Gilead Sciences, Inc (Employee, Shareholder) Ross Martin, PhD, Gilead Sciences, Inc (Employee, Shareholder) Hadas Dvory-Sobol, PhD, Gilead Sciences (Employee, Shareholder) Martin Rhee, MD, Gilead Sciences (Employee, Shareholder) Christian Callebaut, PhD, Gilead Sciences (Employee, Shareholder)

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887. Implementation of Long-acting Injectable Cabotegravir/Rilpivirine for HIV-1 Treatment at a Ryan White-funded Clinic in the U.S. South

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1082 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S535-S535

Author(s):

Lauren F Collins ◽

Della Corbin-Johnson ◽

Meron Asrat ◽

Tonya Rankins ◽

...

Keyword(s):

Virologic Failure ◽

Panel Member ◽

Proton Pump Inhibitor Therapy ◽

Source Distribution ◽

Virologic Suppression ◽

Screening Criteria ◽

Medication Access ◽

Ryan White ◽

Long Acting ◽

Hiv 1

Abstract Background In January 2021, the first ever long-acting injectable (LAI) antiretroviral therapy (ART), cabotegravir/rilpivirine (CAB/RPV), was approved for maintenance HIV-1 treatment in select patients with virologic suppression. LAI-ART has the potential to improve ART adherence, reduce HIV stigma, and promote equity in care outcomes, however, implementation in real-world settings has yet to be evaluated. Methods We launched a pilot LAI-ART program at the largest Ryan White-funded HIV clinic in the Southeast. From 4/14/21 to 5/14/21, providers referred patients interested and willing to switch to LAI-CAB/RPV who met screening criteria. Our interdisciplinary LAI team (Clinician-Pharmacy-Nursing) verified clinical eligibility (HIV-1 < 200 c/ml ≥6 months and no history of virologic failure, resistance to either drug, or chronic HBV infection) and pursued medication access for 28-day oral lead-in and monthly injectable CAB/RPV. We describe demographic and clinical variables of referred PWH and early outcomes in accessing LAI-ART. Results Among 42 referrals, median age was 40.5 (Q1-Q3, 32-52) years, 83% were men, and 76% Black. Payor source distribution was 26% Private, 19% Medicare, 10% Medicaid, and 45% ADAP. At the time of referral, median CD4 count was 583 (Q1-Q3, 422-742) cells/mm3 and median sustained HIV-1 RNA < 200 c/ml was 1427 (Q1-Q3, 961-2534) days. A total of 35 patients (74%) met clinical eligibility for LAI-CAB/RPV, including 4 patients who required a transition off proton pump inhibitor therapy to accommodate oral RPV. Ineligible PWH were excluded due to evidence of RPV resistance (n=5), possible RPV hypersensitivity (n=1), and HIV non-suppression (n=1). The table summarizes the process of pursuing LAI-ART access for the initial 10 enrollees by insurance status. Conclusion Our experience implementing LAI-ART at a Ryan White-funded HIV clinic in the Southern U.S. has been challenged by substantial human resource capital to attain drug, delayed therapy initiation due to insurance denials, and patient ineligibility primarily due to concern for potential RPV resistance. These barriers may perpetuate disparities in ART access and virologic suppression among PWH and need to be urgently addressed so that LAI-ART can be offered equitably. Disclosures Lauren F. Collins, MD, MSc, Nothing to disclose Bradley L. Smith, Pharm.D., AAHIVP, Gilead Sciences, Inc (Advisor or Review Panel member) Wendy Armstrong, MD, Nothing to disclose Jonathan Colasanti, MD, Integritas CME (Consultant, develop and deliver CME content around Rapid Entry/Rapid ART)

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Faculty Opinions recommendation of Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727847958.793541123 ◽

2018 ◽

Author(s):

Anthony Harries ◽

Kudakwashe C Takarinda

Keyword(s):

Open Label ◽

Open Label Phase ◽

Long Acting ◽

Hiv 1

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Discordant Outcomes following Failure of Antiretroviral Therapy Are Associated with Substantial Differences in Human Immunodeficiency Virus-Specific Cellular Immunity

Journal of Virology ◽

10.1128/jvi.77.10.6041-6049.2003 ◽

2003 ◽

Vol 77 (10) ◽

pp. 6041-6049 ◽

Cited By ~ 20

Author(s):

David A. Price ◽

George Scullard ◽

Annette Oxenius ◽

Ruth Braganza ◽

Simon A. Beddows ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Antiretroviral Therapy ◽

T Lymphocyte ◽

Virologic Failure ◽

Multiple Drug Resistance ◽

Testable Hypothesis ◽

Plasma Virus ◽

Immunodeficiency Virus ◽

Lymphocyte Responses ◽

Hiv 1

ABSTRACT Many individuals chronically infected with human immunodeficiency virus type 1 (HIV-1) experience a recrudescence of plasma virus during continuous combination antiretroviral therapy (ART) due either to the emergence of drug-resistant viruses or to poor compliance. In most cases, virologic failure on ART is associated with a coincident decline in CD4+ T lymphocyte levels. However, a proportion of discordant individuals retain a stable or even increasing CD4+ T lymphocyte count despite virological failure. In order to address the nature of these different outcomes, we evaluated virologic and immunologic variables in a prospective, single-blinded, nonrandomized cohort of 53 subjects with chronic HIV-1 infection who had been treated with continuous ART and monitored intensively over a period of 19 months. In all individuals with detectable viremia on ART, multiple drug resistance mutations with similar impacts on viral growth kinetics were detected in the pol gene of circulating plasma virus. Further, C2V3 env gene analysis demonstrated sequences indicative of CCR5 coreceptor usage in the majority of those with detectable plasma viremia. In contrast to this homogeneous virologic pattern, comprehensive screening with a range of antigens derived from HIV-1 revealed substantial immunologic differences. Discordant subjects with stable CD4+ T lymphocyte counts in the presence of recrudescent virus demonstrated potent virus-specific CD4+ and CD8+ T lymphocyte responses. In contrast, subjects with virologic failure associated with declining CD4+ T lymphocyte counts had substantially weaker HIV-specific CD4+ T lymphocyte responses and exhibited a trend towards weaker HIV-specific CD8+ T lymphocyte responses. Importantly the CD4+ response was sustained over periods as long as 11 months, confirming the stability of the phenomenon. These correlative data lead to the testable hypothesis that the consequences of viral recrudescence during continuous ART are modulated by the HIV-specific cellular immune response.

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Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso

Journal of Public Health in Africa ◽

10.4081/jphia.2018.767 ◽

2018 ◽

Author(s):

Serge Theophile Soubeiga ◽

Bapio Valéry Jean Telesphore Elvira Bazie ◽

Tegwindé Rebeca Compaore ◽

Abdoul Karim Ouattara ◽

Théodora Mahoukèdè Zohoncon ◽

...

Keyword(s):

Drug Resistance ◽

Burkina Faso ◽

Virologic Failure ◽

Public Health Problem ◽

Local Data ◽

Immunodeficiency Virus ◽

Women And Children ◽

Hiv 1 ◽

Genetic Analyzer

The emergence of HIV-1 drug resistance (HIVDR) is a public health problem that affects women and children. Local data of HIVDR is critical to improving their care and treatment. So, we investigated HIVDR in mothers and infants receiving antiretroviral therapy (ART) at Saint Camille Hospital of Ouagadougou, Burkina Faso. This study included 50 mothers and 50 infants on ART. CD4 and HIV-1 viral load were determined using FACSCount and Abbott m2000rt respectively. HIVDR was determined in patients with virologic failure using ViroSeq HIV-1 Genotyping System kit on the 3130 Genetic Analyzer. The median age was 37.28 years in mothers and 1.58 year in infants. Sequencing of samples showed subtypes CRF02_AG (55.56%), CRF06_cpx (33.33%) and G (11.11%). M184V was the most frequent and was associated with highlevel resistance to 3TC, FTC, and ABC. Other mutations such as T215F/Y, D67N/E, K70R, and K219Q were associated with intermediate resistance to TDF, AZT, and 3TC. No mutation to LPV/r was detected among mothers and infants. The findings of HIVDR in some mothers and infants suggested the change of treatment for these persons.

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Efficacy, Safety, and Durability of Long-Acting Cabotegravir and Rilpivirine in Adults With HIV-1 Infection: ~5-Year Results From the LATTE-2 Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab439 ◽

2021 ◽

Author(s):

Graham H R Smith ◽

W Keith Henry ◽

Daniel Podzamczer ◽

Maria Del Mar Masiá ◽

Christopher J Bettacchi ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Adverse Events ◽

Maintenance Therapy ◽

Comparable Efficacy ◽

Maintenance Period ◽

Injection Site Reactions ◽

Long Acting ◽

Hiv 1 ◽

Extension Period

Abstract Background In the LATTE-2 phase IIb study, long-acting (LA) injectable cabotegravir + rilpivirine dosed every 8 weeks (Q8W) or 4 weeks (Q4W) demonstrated comparable efficacy with daily oral antiretroviral therapy (ART) through 96 weeks in ART-naive adults with HIV-1. Here we report efficacy, tolerability, and safety of cabotegravir + rilpivirine LA over ~5 years. Methods After 20 weeks of oral cabotegravir + abacavir/lamivudine, participants were randomized to cabotegravir + rilpivirine LA Q8W or Q4W or continue oral ART through the 96-week maintenance period. In the extension period through Week 256, participants continued their current LA regimen (randomized Q8W/Q4W groups) or switched from oral ART to Q8W or Q4W LA therapy (extension-switch groups). Endpoints assessed included proportion of participants with HIV-1 RNA <50 copies/mL (Snapshot algorithm) and adverse events (AEs). Results At Week 256, 186 (81%) of 230 participants in randomized Q8W/Q4W groups and 41 (93%) of 44 participants in extension-switch groups had HIV-1 RNA <50 copies/mL. No protocol-defined virologic failures occurred after Week 48. Injection-site reactions infrequently resulted in discontinuation (4 [2%] and 1 [2%] participants in randomized Q8W/Q4W and extension-switch groups, respectively). Three participants in randomized Q8W/Q4W groups experienced drug-related serious AEs, including 1 fatal serious AE (Q4W group); none occurred in extension-switch groups. Of 25 participants with AEs leading to withdrawal, 20 were in the randomized Q4W group; no AE leading to withdrawal occurred in >1 participant. Conclusions Cabotegravir + rilpivirine LA exhibited long-term efficacy and tolerability, demonstrating its durability as maintenance therapy for HIV-1 infection (ClinicalTrials.gov, NCT02120352).

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