Safety and Efficacy in HIV-1-Infected Patients Treated with Ritonavir-Boosted Saquinavir Mesylate

Abstract Background Early antiretroviral therapy (ART) is recommended for infants with human immunodeficiency virus (HIV) infection. However, few antiretroviral options are available for neonates. Methods The Early Infant Treatment Study in Botswana tested HIV-exposed infants within 96 hours of birth, and HIV-infected infants started nevirapine (NVP) 6 mg/kg twice daily, zidovudine (ZDV), and lamivudine (3TC) at age < 7 days. NVP trough concentrations were tested at 1 and 2 weeks. NVP was switched to ritonavir-boosted lopinavir (LPV/r) at week 2, 3, 4, or 5 according to delivery gestational age. Results Forty HIV-infected infants started ART at median age 2 days (range, 1–5 days). NVP trough concentrations were highly variable and below therapeutic target (3000 ng/mL) for 50% of 2-week measurements; concentrations did not correlate with viral decline at weeks 2, 4, or 12. Two deaths unrelated to ART occurred through 24 weeks. Only 1 unscheduled treatment modification was required. Within 4 weeks of transition to LPV/r, 9 (22.5%) had transient HIV RNA increases, likely due to poor LPV/r palatability. At 12 weeks, 22 (55%) of 40 were <40 copies/mL (93% <400 copies/mL); by 24 weeks, 27 of 38 (71%) were < 40 copies/mL (84% < 400 copies/mL). HIV-1 RNA response at 12 and 24 weeks did not differ by baseline HIV RNA or other factors. Conclusions NVP/ZDV/3TC started in the first week of life was safe and effective, even when trough NVP levels were below target. Transient viral increases occurred following transition to LPV/r, but by 12 and 24 weeks most children achieved and maintained viral suppression. Clinical Trials Registration U01AII4235.

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Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs

npj Vaccines ◽

10.1038/s41541-020-00252-w ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Maria Blasi ◽

Donatella Negri ◽

Kevin O. Saunders ◽

Erich J. Baker ◽

Hannah Stadtler ◽

...

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Lentiviral Vector ◽

Rhesus Macaques ◽

Infected Individual ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Safety And Efficacy ◽

Env Protein ◽

Hiv 1

AbstractA preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactive neutralizing antibodies (bnAbs). One strategy to achieve this goal is to define envelope (Env) evolution that drives bnAb development in infection and to recreate those events by vaccination. In this study, we report the immunogenicity, safety, and efficacy in rhesus macaques of an SIV-based integrase defective lentiviral vector (IDLV) expressing sequential gp140 Env immunogens derived from the CH505 HIV-1-infected individual who made the CH103 and CH235 bnAb lineages. Immunization with IDLV expressing sequential CH505 Envs induced higher magnitude and more durable binding and neutralizing antibody responses compared to protein or DNA +/− protein immunizations using the same sequential envelopes. Compared to monkeys immunized with a vector expressing Envs alone, those immunized with the combination of IDLV expressing Env and CH505 Env protein demonstrated improved durability of antibody responses at six months after the last immunization as well as lower peak viremia and better virus control following autologous SHIV-CH505 challenge. There was no evidence of vector mobilization or recombination in the immunized and challenged monkeys. Although the tested vaccines failed to induce bnAbs and to mediate significant protection following SHIV-challenge, our results show that IDLV proved safe and successful at inducing higher titer and more durable immune responses compared to other vaccine platforms.

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Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: week 96 results of the phase 3 BRIGHTE study

The Lancet HIV ◽

10.1016/s2352-3018(20)30240-x ◽

2020 ◽

Vol 7 (11) ◽

pp. e740-e751 ◽

Cited By ~ 3

Author(s):

Max Lataillade ◽

Jacob P Lalezari ◽

Michael Kozal ◽

Judith A Aberg ◽

Gilles Pialoux ◽

...

Keyword(s):

Phase 3 ◽

Safety And Efficacy ◽

Hiv 1

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The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women

AIDS ◽

10.1097/qad.0b013e32835c208b ◽

2013 ◽

Vol 27 (5) ◽

pp. 739-748 ◽

Cited By ~ 42

Author(s):

Angela P.H. Colbers ◽

David A. Hawkins ◽

Andrea Gingelmaier ◽

Kabamba Kabeya ◽

Jürgen K. Rockstroh ◽

...

Keyword(s):

Pregnant Women ◽

Safety And Efficacy ◽

Hiv 1

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Safety and efficacy of sperm washing in HIV-1-serodiscordant couples where the male is infected: results from the European CREAThE network

AIDS ◽

10.1097/qad.0b013e3282703879 ◽

2007 ◽

Vol 21 (14) ◽

pp. 1909-1914 ◽

Cited By ~ 132

Author(s):

Louis Bujan ◽

Lital Hollander ◽

Mathieu Coudert ◽

Carole Gilling-Smith ◽

Alexandra Vucetich ◽

...

Keyword(s):

Serodiscordant Couples ◽

Safety And Efficacy ◽

Sperm Washing ◽

Hiv 1

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Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in antiretroviral-experienced subjects: week 48 analysis of AI438011, a Phase IIb, randomized controlled trial

Antiviral Therapy ◽

10.3851/imp3112 ◽

2016 ◽

Vol 22 (3) ◽

pp. 215-223 ◽

Cited By ~ 11

Author(s):

Melanie Thompson ◽

◽

Jacob P Lalezari ◽

Richard Kaplan ◽

Yvett Pinedo ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Controlled Trial ◽

Safety And Efficacy ◽

Randomized Controlled ◽

Hiv 1

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Evaluation of safety and efficacy of RNAi against HIV-1 in the human immune system (Rag-2-/-γc-/-) mouse model

Gene Therapy ◽

10.1038/gt.2008.124 ◽

2008 ◽

Vol 16 (1) ◽

pp. 148-153 ◽

Cited By ~ 59

Author(s):

O ter Brake ◽

N Legrand ◽

K J von Eije ◽

M Centlivre ◽

H Spits ◽

...

Keyword(s):

Immune System ◽

Mouse Model ◽

Human Immune System ◽

Safety And Efficacy ◽

Human Immune ◽

Hiv 1

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Hydroxyurea in combination with didanosine and stavudine in antiretroviral-experienced HIV-infected subjects with a review of the literature

International Journal of STD & AIDS ◽

10.1258/095646203321605576 ◽

2003 ◽

Vol 14 (5) ◽

pp. 350-355 ◽

Cited By ~ 7

Author(s):

R Rossero ◽

D M Asmuth ◽

J J Grady ◽

D S McKinsey ◽

S Green ◽

...

Keyword(s):

Viral Load ◽

T Cell ◽

Randomized Study ◽

Transcriptase Inhibitor ◽

Response To Therapy ◽

Safety And Efficacy ◽

Viral Loads ◽

Cell Counts ◽

Withdrawal Of Therapy ◽

Hiv 1

The safety and efficacy of hydroxyurea with didanosine in combination with stavudine in nucleoside reverse-transcriptase inhibitor (NRTI)-experienced patients was investigated. Entry criteria included HIV-1 infected, NRTI-experienced adults, with CD4+ counts 50-550 cells/mm3 and viral loads ≥12,500 copies/mL. Subjects were treated with didanosine 200 mg twice a day (BID), stavudine 40 mg BID, and hydroxyurea 1000 mg daily for 16 weeks. Thirty-one HIV-1 subjects with mean bDNA viral load 1×105 log10 copies/mL and mean CD4+ T-cell counts of 231 cells/mm3 were enrolled. A 1.3 log10 decrease in mean viral load was seen at 12 weeks of therapy. Prior didanosine use resulted in a more rapid response to therapy compared with prior zidovudine use. Side effects consisting of neutropenia, pancreatitis, and peripheral neuropathy occurred in four subjects and resolved upon withdrawal of therapy. This non-randomized study in subjects with a mean CD4+ T-cell count of 230 cells/mm3 demonstrates the antiviral activity of hydroxyurea+didanosine and stavudine. Toxicities related to therapy need to be followed closely. The results support the need for a randomized, prospective study to determine the safety and efficacy of hydroxyurea plus didanosine in antiretroviral-experienced patients with CD4+ cell counts below 300 cells/mm3.

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Immunogenicity, safety and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs

10.1101/2020.03.06.980680 ◽

2020 ◽

Author(s):

Blasi Maria ◽

Negri Donatella ◽

Saunders O Kevin ◽

Baker J Erich ◽

Stadtler Hannah ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Lentiviral Vector ◽

Rhesus Macaques ◽

Infected Individual ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Safety And Efficacy ◽

Broadly Neutralizing Antibody ◽

Env Protein ◽

Hiv 1

AbstractA preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactive neutralizing antibodies (bnAbs). One strategy to achieve this goal is to define envelope (Env) evolution that drives bnAb development in infection and to recreate those events by vaccination. In this study we report the immunogenicity, safety and efficacy in rhesus macaques of an SIV-based integrase defective lentiviral vector (IDLV) expressing sequential gp140 Env immunogens derived from the CH505 HIV-1-infected individual who made the CH103 and CH235 bnAb lineages. Immunization with IDLV expressing sequential CH505 Env induced higher magnitude and more durable binding and neutralizing antibody responses compared to protein or DNA +/- protein immunizations using the same sequential envelopes. Compared to monkeys immunized with vector expressing Envs alone, those immunized with the combination of IDLV expressing Env and CH505 Env protein demonstrated improved durability of antibody responses at six month after the last immunization as well as lower peak viremia and better virus control following autologous SHIV-CH505 challenge. There was no evidence of vector mobilization or recombination in the immunized and challenged monkeys. Our results show that while IDLV proved safe and successful at inducing higher titer and more durable immune responses compared to other vaccine platforms, the use of non-stabilized sequential envelope trimers did not induce broadly neutralizing antibody responses.

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