Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption.

BACKGROUND: The discovery of potent and broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus (HIV) has made passive immunization a potential strategy for the prevention and treatment of HIV infection. We sought to determine whether passive administration of VRC01, a bNAb targeting the HIV CD4-binding site, can safely prevent or delay plasma viral rebound after the discontinuation of antiretroviral therapy (ART). METHODS: We conducted two open-label trials (AIDS Clinical Trials Group [ACTG] A5340 and National Institutes of Health [NIH] 15-I-0140) of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of VRC01 in persons with HIV infection who were undergoing interruption of ART. RESULTS: A total of 24 participants were enrolled, and one serious alcohol-related adverse event occurred. Viral rebound occurred despite plasma VRC01 concentrations greater than 50 µg per milliliter. The median time to rebound was 4 weeks in the A5340 trial and 5.6 weeks in the NIH trial. Study participants were more likely than historical controls to have viral suppression at week 4 (38% vs. 13%, P=0.04 by a two-sided Fisher's exact test in the A5340 trial; and 80% vs. 13%, P<0.001 by a two-sided Fisher's exact test in the NIH trial) but the difference was not significant at week 8. Analyses of virus populations before ART as well as before and after ART interruption showed that VRC01 exerted pressure on rebounding virus, resulting in restriction of recrudescent viruses and selection for preexisting and emerging antibody neutralization-resistant virus. CONCLUSIONS: VRC01 slightly delayed plasma viral rebound in the trial participants, as compared with historical controls, but it did not maintain viral suppression by week 8. In the small number of participants enrolled in these trials, no safety concerns were identified with passive immunization with a single bNAb (VRC01). (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTG A5340 and NIH 15-I-0140 ClinicalTrials.gov numbers, NCT02463227 and NCT02471326 .).

Leveraging Cancer Therapeutics for the HIV Cure Agenda: Current Status and Future Directions.

Despite effective antiretroviral therapy (ART) and undetectable HIV RNA in the plasma, latent replication-competent HIV persists indefinitely in long-lived cells. Cessation of ART results in rebound of HIV from these persistent reservoirs. While this was thought to be an insurmountable obstacle to viral eradication, recent cases suggest otherwise. To date one patient has been "cured" of HIV and several others have been able to interrupt ART without viral rebound for prolonged periods. These events have sparked renewed interest in developing strategies that will allow eradication of HIV in infected individuals. We review the current knowledge of HIV latency and the viral reservoir, describe the potential utility of emerging cancer therapeutics in HIV cure research with an emphasis on pathways implicated in reservoir persistence, and outline opportunities and challenges in the context of the current clinical trial and regulatory environment.

Determination of total potentially available nucleosides in human milk from Asian women.

OBJECTIVE: The objective was to measure the total potentially available nucleosides (TPAN) in breast milk from Asian women. METHODS: One hundred sixty milk samples were collected from 135 healthy, lactating women in Hong Kong, the Philippines, and Singapore at four stages of lactation: colostrum (1 to 3 days postpartum), transitional (7 to 10 days postpartum), early mature (28 to 35 days postpartum), and late mature (90 to 100 days postpartum). Samples were pooled by site and stage of lactation before analysis. RESULTS: The mean TPAN concentration was 203 microM/L (69.4 mg/L corrected for recovery). Average TPAN concentrations were 171.9 microM/L in colostrum, 208.1 microM/L in transitional milk, 221.6 microM/L in early mature milk, and 210.6 microM/L in late mature milk, with no notable differences between countries. The major sources of nucleosides were RNA (43.3% of TPAN) and free nucleotides (39.9% of TPAN). The average percentages of cytidine, uridine, guanosine, and adenosine monophosphates were 44.5%, 23.1%, 16.5%, and 16.1% of TPAN, respectively. The sources of nucleosides and percentages of nucleotide bases were similar for all stages of lactation. Over 91% of the TPAN was present in the non-cellular component except in colostrum. CONCLUSIONS: The average TPAN level in Asian women is similar to that in European and American women, and free nucleotides in human milk represent less than half of the TPAN.