• Human Immunodeficiency Virus (HIV) weakens our ability to fight infections and disease
  • There’s no cure for HIV/AIDS
  • Stem cell transplant and gene therapy may be very promising treatments for HIV/AIDS in the future

Introduction – Human Immunodeficiency Virus (HIV) is a lentivirus (a subgroup of retrovirus) that damages the cells in your immune system (especially CD4+Tcells) and weakens your ability to fight infections and disease (1). Two genetically different but related forms of HIV, called HIV1 and HIV2 have been isolated from patients. HIV1 is the most common type associated with AIDS in the United States, Europe and Central Africa, whereas HIV2 causes a similar disease principally in West Africa (2). To enter target white blood cells, HIV-1 most frequently uses the chemokine receptors CCR5 and/or CXCR4 as co-receptors. CCR5 and CXCR4 are expressed on the surface of host immune cells whereby they provide a mechanism of entry for the HIV-1 virus to infect the cell (3).

Fig.1 A computer generated, simplified representation of HIV particles. The viral envelope membrane is green and the envelope protein is yellow.
Image adapted from (1).

Statistics – It is estimated that 36.9 milion individuals worldwide are affected by HIV (4). Of this 2.1 milion are children(<15 years) (5). About 70% are in Africa, 10% in Asia, 9% in America, 6%in Europe, and 4% in Western Pacific. More than 25 milion deaths are attributable to HIV/AIDS, with 1 to 2 milion deaths annually (2,3). Modelled estimates show that new infections (all ages) declined from a peak of 3.4 million [2.6–4.4 million] in 1996 to 1.8 million [1.4–2.4 million] in 2017 (6). The annual number of global deaths from AIDS-related illness among people living with HIV (all ages) has declined from a peak of 1.9 million [1.4–2.7 million] in 2004 to 940 000 [670 000–1 300 000] in 2017 (6). The latest data from countries show that reductions in deaths due to AIDS-related illness—largely driven by the steady scale-up of antiretroviral therapy (6).


Fig.2. shows statistics of people living with HIV by WHO region, 2017(in million).
Image adapted from (5).

Medication – There’s no cure for HIV/AIDS, but many different drugs are available to control the virus. The current standard treatment for HIV infection is long-term use of antiretroviral therapy (ART), a daily regime of drugs that block steps needed for viral replication. If ART treatment ceases, it leads to a phenomenon termed viral rebound (virus becomes detectable in the bloodstream within days,) that can lead to progression towards AIDS. Unfortunately, ART is not the answer for a cure because the drugs do not kill infected cells in the viral reservoir 4, which is established when virus inserts its genome into the genome of a host immune cell (7). The advent of the new drugs that target the viral reverse transcriptase, protease and integrase enzymes has changed the clinical face of AIDS. With a use of a combination of at least three effective drugs, HIV replication is reduced to below the threshold of detection and remains there for as long as the patient adheres to the therapy. The use of these drugs has brought us to a decrease of the annual death rate from a peak of 16-18 per 100,000 individuals in 1995 to less than 4 per 100,000. ART also has reduced the transmission of the virus (2).

Latest research – In a paper due to be published in Nature on 5 March (is this already published), was elaborated the case of a second patient released from HIV after 18 months without receiving antiretroviral therapy. This resulted after a stem cell transplant that replaced their leukocytes (white blood cells) with HIV resistant versions(8).The first patient, known as the “Berlin patient” —Timothy Brown, is still free of virus. The same stem cell technique was used in treating him in year 2007-2008 (8). The second patient, whose identity has not been disclosed, was diagnosed with HIV in 2003. He began to take the treatment of ART after 9 years. In year 2012 he developed Hodgkin’s lymphoma, and agreed to a stem cell transplant to treat the cancer in 2016 (9).The team lead by Ravindra Grupta—an infectious disease physician at the University of Cambridge, UK— picked a donor who had two copies of a mutation in the CCR5 gene that gives people resistance to HIV infection instead of choosing just any suitable donor. There is about 1% of the lucky people of European descent that have two copies of this mutation and are resistant to HIV infection(9).The transplant resulted successful, and the old leukocytes were replaced by the new resistant versions. In circulating cells of the patient’s blood CCR5 receptor stopped being expressed. Even though it is a very exciting news, the patient is still in remission. This kind of treatment is very aggressive, and it would be more harmful than the disease itself if used in HIV patients, who have do not need a bone marrow transplant. Nonetheless, it proved that the first patient was not an anomaly, and that the cure of HIV may be found with the right effort in doing more research and developing a new gene therapy targeting CCR5. This study opened a path in projecting new strategies to “beat” HIV.

Fig.3. shows a picture of Ravindra Grupta, an infectious disease physician at the University of Cambridge, UK, who led the team in the case that resulted with a second patient released from HIV.
Image adapted from (8).

COPYRIGHT: This article is the property of We Speak Science, a non-profit institution co-founded by Dr. Detina Zalli and Dr. Argita Zalli. The article is written by Veton Guraziu  (University of Prishtina, Kosovo).

References:

1. NHS, HIV and AIDS (3.4.2018) Retrieved, March 20, 2019 from: https://www.nhs.uk/conditions/hiv-and-aids/

2. WebMD,(2017) A visual guide to HIV/AIDS, slideshow nr.3

3. Murphy PM  “Viral exploitation and subversion of the immune system through chemokine mimicry”. Nature Immunology. 2 (2): 116–22.)

4. Vinay Kumar, MBBS, MD, FRCPath, Abul K. Abbas, MBBS, Jon C.Aster, MD, PhD, Robbins basic pathology,Diseases of the immune system, Acquired Immunodeficiency Syndrome pg.173, 174, 175, 176, 177, 10 th edition, Elsevier.

5. World Health Organisation(2017) HIV/AIDS data and statistics, Retrieved March 20, 2019 from: http://www.who.int/hiv/data/en/

6. HIV gov (2016) The global HIV/AIDS epidemic, Retrieved March 20, 2019 from: https://www.hiv.gov/hiv-basics/overview/data-and-trends/global-statistics

7.PMC- US National library of medicine, National Institute of Health (2005) The laboratory diagnosis of HIV infections, Margaret Fearon, MD FRCPC, Retrieve March 20, 2019 from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095005/

8. Nature, 05 March 2019, Second patient free of HIV after stem-cell therapy, Retrieved March 20, 2019 from: https://www.nature.com/articles/d41586-019-00798-3

9. Health 24, 05 March 2019 Second man seems to be free of HIV after stem cell transplant, Retrieved March 20, 2019 from: https://www.health24.com/Medical/HIV-AIDS/News/second-man-seems-to-be-free-of-hiv-after-stem-cell-transplant-20190305