scholarly journals Long-term Clinical Follow-up, without Antiretroviral Therapy, of Patients with Chronic HIV-1 Infection with Good Virological Response to Structured Treatment Interruption

2004 ◽  
Vol 39 (4) ◽  
pp. 569-574 ◽  
Author(s):  
E. Florence ◽  
F. Garcia ◽  
M. Plana ◽  
E. Fumero ◽  
P. Castro ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Virological Response ◽  
Treatment Interruption ◽  
Hiv 1

scholarly journals Plasticity of the Immune System in Children Following Treatment Interruption in HIV-1 Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Katrine Schou Sandgaard ◽  
Ben Margetts ◽  
Teresa Attenborough ◽  
Triantafylia Gkouleli ◽  
Stuart Adams ◽  
...  
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
T Cell Receptor ◽  
Treatment Interruption ◽  
Cell Receptor ◽  
Continuous Treatment ◽  
Thymic Output ◽  
Receptor Repertoire ◽  
Hiv 1

It is intriguing that, unlike adults with HIV-1, children with HIV-1 reach a greater CD4+ T cell recovery following planned treatment cessation. The reasons for the better outcomes in children remain unknown but may be related to increased thymic output and diversity of T cell receptor repertoires. HIV-1 infected children from the PENTA 11 trial tolerated planned treatment interruption without adverse long-term clinical, virological, or immunological consequences, once antiretroviral therapy was re-introduced. This contrasts to treatment interruption trials of HIV-1 infected adults, who had rapid changes in T cells and slow recovery when antiretroviral therapy was restarted. How children can develop such effective immune responses to planned treatment interruption may be critical for future studies. PENTA 11 was a randomized, phase II trial of planned treatment interruptions in HIV-1-infected children (ISRCTN 36694210). In this sub-study, eight patients in long-term follow-up were chosen with CD4+ count>500/ml, viral load <50c/ml at baseline: four patients on treatment interruption and four on continuous treatment. Together with measurements of thymic output, we used high-throughput next generation sequencing and bioinformatics to systematically organize memory CD8+ and naïve CD4+ T cell receptors according to diversity, clonal expansions, sequence sharing, antigen specificity, and T cell receptor similarities following treatment interruption compared to continuous treatment. We observed an increase in thymic output following treatment interruption compared to continuous treatment. This was accompanied by an increase in T cell receptor clonal expansions, increased T cell receptor sharing, and higher sequence similarities between patients, suggesting a more focused T cell receptor repertoire. The low numbers of patients included is a limitation and the data should be interpreted with caution. Nonetheless, the high levels of thymic output and the high diversity of the T cell receptor repertoire in children may be sufficient to reconstitute the T cell immune repertoire and reverse the impact of interruption of antiretroviral therapy. Importantly, the effective T cell receptor repertoires following treatment interruption may inform novel therapeutic strategies in children infected with HIV-1.

scholarly journals Is long-term virological response related to CCR5 Δ32 deletion in HIV-1-infected patients started on highly active antiretroviral therapy?

HIV Medicine ◽  
2010 ◽  
Vol 11 (4) ◽  
pp. 239-244 ◽  
Author(s):  
J-J Laurichesse ◽  
A Taieb ◽  
C Capoulade-Metay ◽  
C Katlama ◽  
V Villes ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Virological Response ◽  
Highly Active Antiretroviral Therapy ◽  
Highly Active ◽  
Hiv 1

scholarly journals 1029. Long-Term Patient Adherence and Management of Treatment Interruptions With Long-Acting Injectable Cabotegravir + Rilpivirine for Maintenance Therapy in Phase IIb/III Studies

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S544-S544
Author(s):  
Paula Teichner ◽  
Sterling Wu ◽  
Feifan Zhang ◽  
David Dorey ◽  
Ronald D’Amico ◽  
...  
Keyword(s):  
Patient Adherence ◽  
Treatment Interruption ◽  
Phase Iii ◽  
Virologic Suppression ◽  
Pivotal Phase ◽  
Treatment Interruptions ◽  
Long Acting ◽  
Hiv 1

Abstract Background Cabotegravir (CAB) and rilpivirine (RPV) are under development as a novel long-acting (LA) regimen for maintenance of HIV virologic suppression. Pooled data from pivotal phase III trials demonstrated noninferiority of CAB + RPV LA given as gluteal intramuscular injections vs current antiretroviral regimen (CAR) on the primary endpoint of HIV-1 ribonucleic acid (RNA) ≥50c/mL at Week 48, with high levels of adherence. Long-term adherence to dosing visits and outcomes after use of oral CAB+RPV to cover planned missed injections in FLAIR through Week 96 and in LATTE-2 through Week 256 is reported here. Methods Virologically suppressed participants (HIV-1 RNA < 50c/mL) were randomized to switch to CAB+RPV LA or to continue CAR. On-time injections occurred every 4 weeks or every 8 weeks (LATTE-2 only) within a ±7-day dosing window of the projected dosing date. Adherence to LA therapy was calculated as the number of on-time injection visits divided by the number of expected dosing visits through the period of follow up. Injection visits outside the prespecified window and missed injection visits with or without use of oral dosing were characterized. Results Of 6005 expected injection visits through Week 96 in FLAIR, 97% of injections were given within the allowed ±7-day dosing window, with 43% on the projected dosing date. 45 (< 1%) injection visits were early and 107 (2%) were late. Adherence to 9803 expected injection visits in LATTE-2, through Week 256, was similarly high, with 96% of injections given within the allowed ±7-day dosing window and 39% on the projected dosing date. For 31 missed injection visits in 18 participants across both trials, 30 were covered with oral CAB+RPV, with all participants maintaining HIV-1 RNA < 50c/mL through the last study visit. In those participants who used oral CAB + RPV for planned treatment interruptions, 3 had repeat use on ≥2 separate occasions. Conclusion Participants maintained high levels of long-term adherence to CAB+RPV LA, through 2-5 years of follow up, with 97% of injections given within the ±7-day dosing window in the FLAIR and LATTE-2 clinical trials. Oral CAB+RPV to cover planned missed visits provides an effective strategy to maintain virologic suppression during short periods of LA treatment interruption. Disclosures Paula Teichner, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Sterling Wu, PhD, GlaxoSmithKline (Employee, Shareholder) David Dorey, MMATH, GlaxoSmithKline Inc. (Employee, Shareholder) Ronald D’Amico, DO, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Sandy Griffith, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Kenneth Sutton, MA, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Cynthia C. McCoig, MD, ViiV Healthcare (Employee) Joseph Polli, PhD, FAAPS, ViiV Healthcare (Employee) David Margolis, MD, MPH, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Rodica Van Solingen-Ristea, MD, Janssen R&D (Employee) Kati Vandermeulen, M.SC., Janssen Pharmaceutica (Employee, Shareholder) William Spreen, PharmD, ViiV Healthcare (Employee, Shareholder) Parul Patel, PharmD, ViiV Healthcare (Employee)

Long-term survival and immuno-virological response of African HIV-1-infected children to highly active antiretroviral therapy regimens

AIDS ◽  
2006 ◽  
Vol 20 (18) ◽  
pp. 2315-2319 ◽  
Author(s):  
François Rouet ◽  
Patricia Fassinou ◽  
André Inwoley ◽  
Marie-France Anaky ◽  
Alain Kouakoussui ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Virological Response ◽  
Highly Active Antiretroviral Therapy ◽  
Term Survival ◽  
Long Term Survival ◽  
Highly Active ◽  
Hiv 1

scholarly journals Impact of long-term antiretroviral therapy on gut and oral microbiotas in HIV-1-infected patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mayumi Imahashi ◽  
Hirotaka Ode ◽  
Ayumi Kobayashi ◽  
Michiko Nemoto ◽  
Masakazu Matsuda ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Strand Transfer ◽  
Intestinal Dysbiosis ◽  
Α Diversity ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1 ◽  
Over Time

AbstractIn HIV-1-infected patients, antiretroviral therapy (ART) is a key factor that may impact commensal microbiota and cause the emergence of side effects. However, it is not fully understood how long-term ART regimens have diverse impacts on the microbial compositions over time. Here, we performed 16S ribosomal RNA gene sequencing of the fecal and salivary microbiomes in patients under different long-term ART. We found that ART, especially conventional nucleotide/nucleoside reverse transcriptase inhibitor (NRTI)-based ART, has remarkable impacts on fecal microbial diversity: decreased α-diversity and increased ß-diversity over time. In contrast, dynamic diversity changes in the salivary microbiome were not observed. Comparative analysis of bacterial genus compositions showed a propensity for Prevotella-enriched and Bacteroides-poor gut microbiotas in patients with ART over time. In addition, we observed a gradual reduction in Bacteroides but drastic increases in Succinivibrio and/or Megasphaera under conventional ART. These results suggest that ART, especially NRTI-based ART, has more suppressive impacts on microbiota composition and diversity in the gut than in the mouth, which potentially causes intestinal dysbiosis in patients. Therefore, NRTI-sparing ART, especially integrase strand transfer inhibitor (INSTI)- and/or non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens, might alleviate the burden of intestinal dysbiosis in HIV-1-infected patients under long-term ART.

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