Early HIV RNA Decay During Raltegravir-containing Regimens Exhibits Two Distinct Subphases Early HIV RNA Decay During Raltegravir-containing Regimens Exhibits Two Distinct Subphases (1a and 1b).

Topic:

HIV Prevention

Authors:

Andrade A, Guedj J, Rosenkranz SL, Lu D, Mellors J, Kuritzkes DR, Perelson AS, Ribeiro RM; ACTG A5249s protocol team. 

External Link:

Link to article

BACKGROUND: We analyzed the early kinetics with integrase inhibitor treatment to gain new insights into viral dynamics.

METHODOLOGY: We analyzed data from 39 HIV-1 infected, treatment-naive, participants: 28 treated with raltegravir (RAL; multiple doses) monotherapy for 9 days, and 11 with RAL 400 mg twice daily and emtricitabine (200 mg daily)/tenofovir disoproxil fumarate (300 mg daily). Plasma HIV-1 RNA was measured frequently; the data was fitted using a mathematical model of viral dynamics distinguishing between infected cells with unintegrated HIV DNA and productively infected cells. Parameters were estimated using mixed-effect models.

RESULTS: RAL treatment led to a biphasic viral decline with a rapid first phase (1a) lasting approximately 5 days followed by a slower phase (1b). Phase 1a is attributed to the rapid elimination of productively infected cells. Phase 1b reflects the loss of infected cells with nonintegrated provirus due to cell loss and integration of HIV DNA. The half-lives of productively infected cells and of infected cells that had completed reverse transcription but had not yet integrated HIV DNA were approximately 19 h and between 3.6 and 5.8 days, respectively. The effectiveness of RAL in preventing proviral integration was 94% and 99.7%, for the combination therapy and monotherapy groups, respectively.

CONCLUSION: We found that the first phase of viral decay with RAL therapy was composed of two subphases corresponding to the half-lives of infected cells with integrated proviruses and with unintegrated HIV-DNA.

AIDS. 2015 Nov 28;29(18):2419-26. doi: 10.1097/QAD.0000000000000843. PMID: 26558541

Categories

CRS
Topics

Clinical Trials

HPTN 069: A Phase II Randomized, Double-Blind, Study of the...

HPTN 069 is a phase II, four-arm, multisite, randomized, double-blinded trial. To assess the safety and tolerability of four...

Read More

A5354/EARLIER: Effect of Antiretroviral Treatment Initiated...

This study will include people who have very recently been infected with HIV and will start anti-HIV (antiretroviral) drugs...

Read More

HPTN083: A Phase 2b/3 Double Blind Safety and Efficacy Study...

HPTN 083 is a study being done to evaluate the efficacy of the long-acting injectable agent, cabotegravir (CAB LA), for...

Read More

A5349: Rifapentine-containing treatment shortening regimens...

The purpose of this study is to determine whether one or two four-month regimens of tuberculosis treatment are as effective as a...

Read More

P1073: Study of Immune Reconstitution Inflammatory Syndrome...

P1073 is a case controlled prospective, clinical, observational and pathogenesis study of HIV-infected infants and children...

Read More