scholarly journals Safety and Efficacy of Starting Antiretroviral Therapy in the First Week of Life

2020 ◽  
Author(s):  
Kenneth Maswabi ◽  
Gbolahan Ajibola ◽  
Kara Bennett ◽  
Edmund V Capparelli ◽  
Patrick Jean-Philippe ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Viral Suppression ◽  
Safety And Efficacy ◽  
Hiv Rna ◽  
Early Infant ◽  
Immunodeficiency Virus ◽  
Trough Concentrations ◽  
Hiv Exposed ◽  
Hiv 1

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.

scholarly journals Induction of Autophagy to Achieve a Human Immunodeficiency Virus Type 1 Cure

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1798
Author(s):  
Grant R. Campbell ◽  
Stephen A. Spector
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Functional Cure ◽  
Immunodeficiency Virus ◽  
Latently Infected ◽  
Infected Cells ◽  
Hiv 1

Effective antiretroviral therapy has led to significant human immunodeficiency virus type 1 (HIV-1) suppression and improvement in immune function. However, the persistence of integrated proviral DNA in latently infected reservoir cells, which drive viral rebound post-interruption of antiretroviral therapy, remains the major roadblock to a cure. Therefore, the targeted elimination or permanent silencing of this latently infected reservoir is a major focus of HIV-1 research. The most studied approach in the development of a cure is the activation of HIV-1 expression to expose latently infected cells for immune clearance while inducing HIV-1 cytotoxicity—the “kick and kill” approach. However, the complex and highly heterogeneous nature of the latent reservoir, combined with the failure of clinical trials to reduce the reservoir size casts doubt on the feasibility of this approach. This concern that total elimination of HIV-1 from the body may not be possible has led to increased emphasis on a “functional cure” where the virus remains but is unable to reactivate which presents the challenge of permanently silencing transcription of HIV-1 for prolonged drug-free remission—a “block and lock” approach. In this review, we discuss the interaction of HIV-1 and autophagy, and the exploitation of autophagy to kill selectively HIV-1 latently infected cells as part of a cure strategy. The cure strategy proposed has the advantage of significantly decreasing the size of the HIV-1 reservoir that can contribute to a functional cure and when optimised has the potential to eradicate completely HIV-1.

scholarly journals Human Immunodeficiency Virus Type 1 RNA Detected in the Central Nervous System (CNS) After Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells

2018 ◽  
Vol 69 (8) ◽  
pp. 1345-1352 ◽  
Author(s):  
Sarah B Joseph ◽  
Laura P Kincer ◽  
Natalie M Bowman ◽  
Chris Evans ◽  
Michael J Vinikoor ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Human Immunodeficiency Virus ◽  
Nervous System ◽  
Antiretroviral Therapy ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Csf Escape

Abstract Background Human immunodeficiency virus type 1 (HIV-1) populations are detected in cerebrospinal fluid (CSF) of some people on suppressive antiretroviral therapy (ART). Detailed analysis of these populations may reveal whether they are produced by central nervous system (CNS) reservoirs. Methods We performed a study of 101 asymptomatic participants on stable ART. HIV-1 RNA concentrations were cross-sectionally measured in CSF and plasma. In participants with CSF HIV-1 RNA concentrations sufficient for analysis, viral populations were genetically and phenotypically characterized over multiple time points. Results For 6% of participants (6 of 101), the concentration of HIV-1 RNA in their CSF was ≥0.5 log copies/mL above that of plasma (ie, CSF escape). We generated viral envelope sequences from CSF of 3 participants. One had a persistent CSF escape population that was macrophage-tropic, partially drug resistant, genetically diverse, and closely related to a minor macrophage-tropic lineage present in the blood prior to viral suppression and enriched for after ART. Two participants (1 suppressed and 1 not) had transient CSF escape populations that were R5 T cell-tropic with little genetic diversity. Conclusions Extensive analysis of viral populations in 1 participant revealed that CSF escape was from a persistently replicating population, likely in macrophages/microglia, present in the CNS over 3 years of ART. CSF escape in 2 other participants was likely produced by trafficking and transient expansion of infected T cells in the CNS. Our results show that CNS reservoirs can persist during ART and that CSF escape is not exclusively produced by replicating CNS reservoirs.

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

2003 ◽  
Vol 77 (10) ◽  
pp. 6041-6049 ◽  
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.

scholarly journals Human Immunodeficiency Virus Type 2: The Neglected Threat

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1377
Author(s):  
Giancarlo Ceccarelli ◽  
Marta Giovanetti ◽  
Caterina Sagnelli ◽  
Alessandra Ciccozzi ◽  
Gabriella d’Ettorre ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Treatment Options ◽  
The United States ◽  
Global Integration ◽  
Immunodeficiency Virus ◽  
Cell Decline ◽  
Sexual Contacts ◽  
Hiv 1

West Africa has the highest prevalence of human immunodeficiency virus (HIV)-2 infection in the world, but a high number of cases has been recognized in Europe, India, and the United States. The virus is less transmissible than HIV-1, with sexual contacts being the most frequent route of acquisition. In the absence of specific antiretroviral therapy, most HIV-2 carriers will develop AIDS. Although, it requires more time than HIV-1 infection, CD4+ T cell decline occurs more slowly in HIV-2 than in HIV-1 patients. HIV-2 is resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and some protease inhibitors. Misdiagnosis of HIV-2 in patients mistakenly considered HIV-1-positive or in those with dual infections can cause treatment failures with undetectable HIV-1 RNA. In this era of global integration, clinicians must be aware of when to consider the diagnosis of HIV-2 infection and how to test for this virus. Although there is debate regarding when therapy should be initiated and which regimen should be chosen, recent trials have provided important information on treatment options for HIV-2 infection. In this review, we focus mainly on data available and on the insight they offer about molecular epidemiology, clinical presentation, antiretroviral therapy, and diagnostic tests of HIV-2 infection.

scholarly journals A Randomized Switch From Nevirapine-Based Antiretroviral Therapy to Single Tablet Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in Virologically Suppressed Human Immunodeficiency Virus-1-Infected Rwandans

2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Sean E. Collins ◽  
Philip M. Grant ◽  
Francois Uwinkindi ◽  
Annie Talbot ◽  
Eric Seruyange ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Tenofovir Disoproxil Fumarate ◽  
Sub Saharan Africa ◽  
Current Therapy ◽  
Virologic Suppression ◽  
Open Label ◽  
Immunodeficiency Virus ◽  
Sub Saharan ◽  
Hiv 1

Abstract Background.  Many human immunodeficiency virus (HIV)-infected patients remain on nevirapine-based antiretroviral therapy (ART) despite safety and efficacy concerns. Switching to a rilpivirine-based regimen is an alternative, but there is little experience with rilpivirine in sub-Saharan Africa where induction of rilpivirine metabolism by nevirapine, HIV subtype, and dietary differences could potentially impact efficacy. Methods.  We conducted an open-label noninferiority study of virologically suppressed (HIV-1 ribonucleic acid [RNA] < 50 copies/mL) HIV-1-infected Rwandan adults taking nevirapine plus 2 nucleos(t)ide reverse-transcriptase inhibitors. One hundred fifty participants were randomized 2:1 to switch to coformulated rilpivirine-emtricitabine-tenofovir disoproxil fumarate (referenced as the Switch Arm) or continue current therapy. The primary efficacy endpoint was HIV-1 RNA < 200 copies/mL at week 24 assessed by the US Food and Drug Administration Snapshot algorithm with a noninferiority margin of 12%. Results.  Between April and September 2014, 184 patients were screened, and 150 patients were enrolled; 99 patients switched to rilpivirine-emtricitabine-tenofovir, and 51 patients continued their nevirapine-based ART. The mean age was 42 years and 43% of participants were women. At week 24, virologic suppression (HIV-1 RNA level <200 copies/mL) was maintained in 93% and 92% in the Switch Arm versus the continuation arm, respectively. The Switch Arm was noninferior to continued nevirapine-based ART (efficacy difference 0.8%; 95% confidence interval, −7.5% to +12.0%). Both regimens were generally safe and well tolerated, although 2 deaths, neither attributed to study medications, occurred in participants in the Switch Arm. Conclusions.  A switch from nevirapine-based ART to rilpivirine-emtricitabine-tenofovir disoproxil fumarate had similar virologic efficacy to continued nevirapine-based ART after 24 weeks with few adverse events.

scholarly journals Effects of Valproic Acid Coadministration on Plasma Efavirenz and Lopinavir Concentrations in Human Immunodeficiency Virus-Infected Adults

2004 ◽  
Vol 48 (11) ◽  
pp. 4328-4331 ◽  
Author(s):  
Robert DiCenzo ◽  
Derick Peterson ◽  
Kim Cruttenden ◽  
Gene Morse ◽  
Garret Riggs ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Valproic Acid ◽  
Geometric Mean ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Blood Samples ◽  
Immunodeficiency Virus ◽  
Before And After ◽  
Trough Concentrations ◽  
Hiv 1

ABSTRACT Valproic acid (VPA) has the potential to benefit patients suffering from human immunodeficiency virus (HIV)-associated cognitive impairment. The purpose of this study was to determine if VPA affects the plasma concentration of efavirenz (EFV) or lopinavir. HIV type 1 (HIV-1)-infected patients receiving EFV or lopinavir-ritonavir (LPV/r) had 9 or 10 blood samples drawn over 8 to 24 h of a dosing interval at steady state before and after receiving 250 mg of VPA twice daily for 7 days. VPA blood samples drawn before (C 0) and 8 h after the morning dose (8 h) were compared to blood samples from a group of HIV-1-infected subjects who were taking either combined nucleoside reverse transcriptase inhibitors alone or had discontinued antiretroviral therapy. Pharmacokinetic parameters were calculated by noncompartmental analysis, and tests of bioequivalence were based on 90% confidence intervals (CIs) for ratios or differences. The geometric mean ratio (GMR) (90% CI) of the areas under the concentration-time curve from 0 to 24 h (AUC0-24s) of EFV (n = 11) with and without VPA was 1.00 (0.85, 1.17). The GMR (90% CI) of the AUC0-8s of LPV (n = 8) with and without VPA was 1.38 (0.98, 1.94). The differences (90% CI) in mean C 0 and 8-h VPA concentrations versus the control (n = 11) were −1.0 (−9.4, 7.4) μg/ml and −2.1 (−11.1, 6.9) μg/ml for EFV (n = 10) and −5.0 (−13.2, 3.3) μg/ml and −6.7 (−17.6, 4.2) μg/ml for LPV/r (n = 11), respectively. EFV administration alone is bioequivalent to EFV and VPA coadministration. LPV concentrations tended to be higher when the drug was combined with VPA. Results of VPA comparisons fail to raise concern that coadministration with EFV or LPV/r will significantly influence trough concentrations of VPA.

scholarly journals 1265. Monitoring of Human Immunodeficiency Virus (HIV)-Infection Using the Cepheid HIV-1 Qualitative Assay

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S455-S455
Author(s):  
Erin Keizur ◽  
Drew Wood-Palmer ◽  
Maryann Koussa ◽  
Manuel Ocasio ◽  
Mary Jane Rotheram-Borus ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Los Angeles ◽  
Hiv Infection ◽  
Whole Blood ◽  
Viral Rna ◽  
Hiv Rna ◽  
Hiv Dna ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Pcr Test

Abstract Background Human immunodeficiency virus (HIV)-1 RNA quantification is the primary method of monitoring response to antiretroviral therapy. In the U.S. viral RNA testing is recommended for all HIV-infected patients at entry into care, at initiation or modification of therapy, and on a regular basis thereafter. HIV-1 DNA testing may pose additional advantages. For example, proviral DNA may predict early loss of viral suppression. The Cepheid® (Sunnyvale, CA) HIV-1 Qualitative (HIV Qual) assay detects total nucleic acid for both RNA and DNA and provides a qualitative result (HIV detectable or undetectable). Methods We tested participants aged 14–24 years old from the Adolescent Trials Network (ATN) CARES study with known HIV infection in Los Angeles, California and New Orleans, Louisiana. We tested participants using the Cepheid® HIV Qual assay and the quantitative HIV-1 RNA, real-time PCR test using the COBAS P6800 system (Roche, Branchburg, NJ). We used 100 μL of whole blood for the HIV Qual assay and results were provided in 90 minutes. We sent the remainder of the whole blood from the same visit to a commercial laboratory for HIV-RNA PCR testing and results were reported as “detected,” “detected, <20 copies/mL plasma” or “not detected, <20 copies/mL plasma.” We compared HIV Qual and HIV RNA PCR test results from the same visit for each participant. Results Overall, 57 HIV Qual tests were performed with concurrent HIV RNA PCR tests. Of those, 9/15 tests were concordant with HIV viral RNA suppression while 39/42 tests were concordant with HIV viral RNA detection. In 6 cases, the HIV RNA was not detected at <20 copies/mL by the Roche PCR while the HIV Qual assay detected HIV DNA. Of those 6 cases, 3 had subsequent HIV RNA PCR testing. All 3 cases had detectable HIV RNA at their next testing date (214 copies/mL, detected <20 copies/mL, 2130 copies/mL). Conclusion The HIV Qual test is feasible for the monitoring of HIV-infection. Due to its detection of HIV DNA, it may predict future lack of HIV RNA suppression. Disclosures All authors: No reported disclosures.

scholarly journals Antiretroviral Therapy with a Twice-Daily Regimen Containing 400 Milligrams of Indinavir and 100 Milligrams of Ritonavir in Human Immunodeficiency Virus Type 1-Infected Women during Pregnancy

2008 ◽  
Vol 52 (4) ◽  
pp. 1542-1544 ◽  
Author(s):  
Jade Ghosn ◽  
Ines De Montgolfier ◽  
Chantal Cornélie ◽  
Stéphanie Dominguez ◽  
Claire Pérot ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Daily Regimen ◽  
Child Transmission ◽  
Third Trimester ◽  
Safety And Efficacy ◽  
Hiv Rna ◽  
The Third ◽  
Immunodeficiency Virus ◽  
Mother To Child

ABSTRACT We evaluated the safety and efficacy of a twice daily regimen containing 400 mg of indinavir and 100 mg of ritonavir in 32 human immunodeficiency virus (HIV)-infected women during pregnancy. The median indinavir trough concentration was 208 ng/ml during the third trimester. At delivery, 26 of 28 women on indinavir-ritonavir had HIV RNA levels of <200 copies/ml. No infant was HIV infected. These data are encouraging for the use of this combination for prevention of mother-to-child transmission of HIV.

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