Genital reservoir: a barrier to functional cure?
Purpose of review
HIV functional cure requires the elimination or a major reduction of HIV reservoir pool including male and female genital HIV reservoirs. A comprehensive understanding of HIV dynamics in these compartments is mandatory.
Recent findings
Data from chronically HIV-infected therapy-naïve individuals or fully suppressed on combined antiretroviral therapy (cART) or undergoing ART interruptions are now available. Using paired blood/genital samples, HIV-RNA/DNA quantification and sequencing provide new insights on HIV dynamics in genital reservoirs.
Summary
In the absence of cART, HIV shedding in semen a...
Source: Current Opinion in HIV and AIDS - August 3, 2018 Category: Infectious Diseases Tags: PROGRESS IN ACHIEVING LONG-TERM HIV REMISSION: Edited by Jean-Daniel Lelièvre and Timothy J. Henrich Source Type: research
HIV DNA: a clinical marker of HIV reservoirs
Purpose of review
A number studies are currently underway to develop new drugs aimed at reducing the HIV reservoir or achieving ART-free control of HIV infection. Many markers of HIV reservoirs have been proposed, each one having a different meaning. Total HIV DNA dynamics during the course of HIV infection and its predictive value are now well known. This marker allowed to estimate the size of HIV reservoir at different stages of HIV infection in blood, cell subsets and tissues. Therefore, the purpose of this review is timely and relevant, with the objective to discuss how total HIV DNA might be helpful in the clinical ...
Source: Current Opinion in HIV and AIDS - August 3, 2018 Category: Infectious Diseases Tags: PROGRESS IN ACHIEVING LONG-TERM HIV REMISSION: Edited by Jean-Daniel Lelièvre and Timothy J. Henrich Source Type: research
Markers of the HIV-1 reservoir: facts and controversies
Purpose of review
The HIV-1 reservoir is composed of infected cells poised to replicate and spread the virus upon treatment interruption. It constitutes the main obstacle toward an HIV-1 cure. Whether marker(s) may allow the detection of cells that form the reservoir is an outstanding question. Here, we present and discuss recent advances and controversies in the identification and characterization of markers of the HIV-1 reservoir.
Recent findings
Latently infected T cells that persist under successful therapy do not express viral antigens, making their identification challenging. HIV is not equally distributed acros...
Source: Current Opinion in HIV and AIDS - August 3, 2018 Category: Infectious Diseases Tags: PROGRESS IN ACHIEVING LONG-TERM HIV REMISSION: Edited by Jean-Daniel Lelièvre and Timothy J. Henrich Source Type: research
Progress towards obtaining an HIV cure: slow but sure
No abstract available (Source: Current Opinion in HIV and AIDS)
Source: Current Opinion in HIV and AIDS - August 3, 2018 Category: Infectious Diseases Tags: PROGRESS IN ACHIEVING LONG-TERM HIV REMISSION: Edited by Jean-Daniel Lelièvre and Timothy J. Henrich Source Type: research
Editorial introductions
No abstract available (Source: Current Opinion in HIV and AIDS)
Source: Current Opinion in HIV and AIDS - August 3, 2018 Category: Infectious Diseases Tags: Editorial Introduction Source Type: research
Editorial: New HIV drugs 2018 and beyond
No abstract available (Source: Current Opinion in HIV and AIDS)
Source: Current Opinion in HIV and AIDS - June 8, 2018 Category: Infectious Diseases Tags: NEW HIV DRUGS: Edited by Roy M. Gulick Source Type: research
Antiretroviral implants for treatment and prevention of HIV infection
Purpose of review
Poor adherence to oral antiretroviral formulations remains the major barrier to the success of long-term treatment and prevention strategies. Although a number of approaches have been developed for long-acting parenteral delivery of antiretroviral drugs, subcutaneous implants are a particularly promising technology as they may be able to provide protective drugs concentrations for a year or longer following a single implant. This review addresses the current status of preclinical and clinical development of antiretroviral implants.
Recent findings
Subcutaneous implants have been widely used for hormo...
Source: Current Opinion in HIV and AIDS - June 4, 2018 Category: Infectious Diseases Tags: NEW HIV DRUGS: Edited by Roy M. Gulick Source Type: research
Broadly neutralizing antibodies for treatment and prevention of HIV-1 infection
Purpose of review
Several anti-HIV-1 broadly neutralizing antibodies (bNAbs) with exceptional breadth and potency that target different HIV-1 envelope epitopes have been identified. bNAbs are an attractive new strategy for HIV-1 prevention and therapy, and potentially, for long-term remission or cure. Here, we discuss findings from early clinical studies that have evaluated these novel bNAbs.
Recent findings
Phase 1 studies of bNAbs targeting two distinct HIV-1 envelope epitopes have demonstrated their favorable safety and pharmacokinetic profile. Single bNAb infusions led to significant, but transient, decline in vir...
Source: Current Opinion in HIV and AIDS - June 4, 2018 Category: Infectious Diseases Tags: NEW HIV DRUGS: Edited by Roy M. Gulick Source Type: research
Inhibitors of the HIV-1 capsid, a target of opportunity
Purpose of review
To summarize recent advances in the discovery of chemical inhibitors targeting the HIV capsid and research on their mechanisms of action.
Recent findings
HIV infection is critically dependent on functions of the viral capsid. Numerous studies have reported the identification of a variety of compounds that bind to the capsid protein; some of these inhibit reverse transcription and nuclear entry, steps required for infection. Other capsid-targeting compounds appear to act by perturbing capsid assembly, resulting in noninfectious progeny virions. Inhibitors may bind to several different positions on the...
Source: Current Opinion in HIV and AIDS - June 4, 2018 Category: Infectious Diseases Tags: NEW HIV DRUGS: Edited by Roy M. Gulick Source Type: research
Ibalizumab
Purpose of review
Antiretroviral options for patients infected with multiclass resistant HIV-1 warrant the development of new agents with unique mechanisms of action and modes of delivery. Here we review one such agent, ibalizumab, a parenteral CD4 postattachment inhibitor that has demonstrated efficacy as part of combination antiretroviral therapy in the treatment of HIV-1.
Recent findings
In a phase III clinical trial in HIV-infected participants with multiclass antiretroviral drug resistance, the intravenous administration of ibalizumab led to declines in plasma HIV-1 RNA more than 0.5 log in 83% of participants at...
Source: Current Opinion in HIV and AIDS - June 4, 2018 Category: Infectious Diseases Tags: NEW HIV DRUGS: Edited by Roy M. Gulick Source Type: research
The return of PRO 140, a CCR5-directed mAb
Purpose of review
Although antiretroviral therapy has become more potent and tolerable, adherence remains a barrier to continuous viral suppression and new approaches are needed. PRO 140 is a C-C chemokine receptor 5 (CCR5)-directed mAb with potential for weekly subcutaneous dosing. This review discusses data from the PRO 140 clinical development program including emerging data from ongoing efficacy studies.
Recent findings
Phase II development of PRO 140 began over a decade ago, and recently initiated phase IIb and III trials are ongoing in study participants with virologic failure and as monotherapy maintenance in v...
Source: Current Opinion in HIV and AIDS - June 4, 2018 Category: Infectious Diseases Tags: NEW HIV DRUGS: Edited by Roy M. Gulick Source Type: research
Fostemsavir: a new CD4 attachment inhibitor
Purpose of review
Even in the era of modern HAART, antiretroviral (ARV) failure and emergence of drug resistance is still a problem worldwide. New classes with different mechanisms of action are needed to overcome this challenge. After the integrase inhibitors were launched, more than a decade ago, no new classes were added to the ARV armamentarium.
Recent findings
Fostemsavir (FTR) is an attachment inhibitor, active regardless of viral tropism, without cross-resistance to any of the existing ARV compounds. A phase 3 study showed a reduction in plasma viral RNA of 1.21–1.73 log10 copies/ml from baseline after 8 da...
Source: Current Opinion in HIV and AIDS - June 4, 2018 Category: Infectious Diseases Tags: NEW HIV DRUGS: Edited by Roy M. Gulick Source Type: research
Cabotegravir: its potential for antiretroviral therapy and preexposure prophylaxis
Purpose of review
Analyzing the evidence for the strand transfer integrase inhibitor cabotegravir (CAB; GSK744, GSK1265744), its properties and differences from other compounds in the class, as well as reviewing the preclinical and clinical evidence for its potential in antretroviral therapy and medical HIV prevention.
Recent findings
CAB has been investigated both as an oral and an injectable compound. Recent results show that it has promising properties with regards to its potential for parenteral maintenance therapy in combination with other compounds in HIV-infected patients currently suppressed on oral agents, as...
Source: Current Opinion in HIV and AIDS - June 4, 2018 Category: Infectious Diseases Tags: NEW HIV DRUGS: Edited by Roy M. Gulick Source Type: research
Bictegravir
Purpose of review
In this review, we will highlight and discuss the recent efficacy and safety data of bictegravir (BIC), a novel second-generation integrase strand transfer inhibitor (INSTI) that has been recently approved, in coformulation with emtricitabine and tenofovir alafenamide (B/F/TAF), for the treatment of HIV-1 infection in antiretroviral naïve subjects and in those with suppressed viremia.
Recent findings
Preclinical data showed that BIC has a genetic barrier that is higher than that of raltegravir and elvitegravir but is similar to that of dolutegravir (DTG), with retained activity in vitro against isol...
Source: Current Opinion in HIV and AIDS - June 4, 2018 Category: Infectious Diseases Tags: NEW HIV DRUGS: Edited by Roy M. Gulick Source Type: research
Dolutegravir–rilpivirine coformulation
Purpose of review
With prolonged life expectancy in HIV-positive patients on combination antiretroviral therapy, the quest for reducing lifelong drug exposure and minimizing or avoiding the toxicities of combination antiretroviral therapy while maintaining viral suppression has emerged when coformulations of antiretroviral agents with improved convenience, and better tolerability and efficacy became available. This review aims to update the current experience with the novel two-drug combination of dolutegravir (DTG) and rilpivirine (RPV) and elucidate the possible applications and limitations of coformulated DTG–RPV in...
Source: Current Opinion in HIV and AIDS - June 4, 2018 Category: Infectious Diseases Tags: NEW HIV DRUGS: Edited by Roy M. Gulick Source Type: research
