Lessons Learned From Failures and Success Stories of HIV Breakthroughs: Are We Getting Closer to an HIV Cure?

V Kalidasan,Kumitaa Theva Das

doi:10.3389/fmicb.2020.00046

Abstract

There is a continuous search for an HIV cure as the success of ART in blocking HIV replication and the role of CD4+ T cells in HIV pathogenesis and immunity do not entirely eradicate HIV. The Berlin patient, who is virus-free, serves as the best model for a ‘sterilizing cure’ and many experts are trying to mimic this approach in other patients. Although failures were reported among Boston and Essen patients, the setbacks have provided valuable lessons to strengthen cure strategies. Following the Berlin patient, two more patients known as London and Düsseldorf patients might be the second and third person to be cured of HIV. In all the cases, the patients underwent chemotherapy regimen due to malignancy and hematopoietic stem cell transplantation (HSCT) which required matching donors for CCR5Δ32 mutation – an approach that may not always be feasible. The emergence of newer technologies, such as long-acting slow-effective release ART (LASER ART) and CRISPR/Cas9 could potentially overcome the barriers due to HIV latency and persistency and eliminate the need for CCR5Δ32 mutation donor. Appreciating the failure and success stories learned from these HIV breakthroughs would provide some insight for future HIV eradication and cure strategies.

Highlights

As of 2018, the Joint United Nations Programme on human immunodeficiency virus (HIV)/AIDS (UNAIDS) reported that 37.9 million people were living with HIV, of which 14.6 million people had no access to antiretroviral therapy (ART)
Valuable lessons learned from this success story (Allers et al, 2011; Mitsuyasu, 2013; Yukl et al, 2013; Peterson and Kiem, 2019) include: (i) graft-versus-host disease (GVHD) in which donor-derived immune response subsequently clears persistent HIV-1 infected cells, resulting in reduced HIV reservoir, (ii) application of anti-cancer strategies, such as cytotoxic drugs, chemotherapy agents to eliminate HIV-infected cells, and (iii) not all patients who have undergone CCR5 32 mutation hematopoietic stem cell transplantation (HSCT) will achieve a conceivable cure, such as the Essen patient, which suggests that personalized strategies are needed
HIV persistence, either pre-integration or post-integration latency, appears to be a significant challenge. The latter is more critical, as HIV DNA which integrates into the resting CD4+ T cells remain in the cells for long durations, inaccessible to ART or immune recognition

Summary

Kalidasan and Kumitaa Theva Das*

There is a continuous search for an HIV cure as the success of ART in blocking HIV replication and the role of CD4+ T cells in HIV pathogenesis and immunity do not entirely eradicate HIV. Failures were reported among Boston and Essen patients, the setbacks have provided valuable lessons to strengthen cure strategies. The patients underwent chemotherapy regimen due to malignancy and hematopoietic stem cell transplantation (HSCT) which required matching donors for CCR5 32 mutation – an approach that may not always be feasible. The emergence of newer technologies, such as long-acting slow-effective release ART (LASER ART) and CRISPR/Cas could potentially overcome the barriers due to HIV latency and persistency and eliminate the need for CCR5 32 mutation donor. Appreciating the failure and success stories learned from these HIV breakthroughs would provide some insight for future HIV eradication and cure strategies

INTRODUCTION

Findings

CONCLUSION AND FUTURE DIRECTIONS