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The HIV Pandemic: Past, Present and Future [Part Two]

Editor: This article is the second of a two-part series. Check out Part One here.

In Part One of the article series, we began to explore HIV (human immunodeficiency virus), specifically HIV-1, which is the deadly virus behind a global pandemic that is still ravaging many parts of our world today.

To summarise, HIV-1 is a retrovirus that infects CD4+ cells and if left untreated, can cause AIDS (acquired immune deficiency syndrome). It has a lifecycle with several unique features such as the stage of reverse transcription (i.e. viral RNA genome is used as a template to produce DNA). Also, it integrates into its host cell’s genome to produce a latent HIV reservoir that is hidden from the immune system and can remain dormant (meaning inactive) for years.

In Part 2, we will look at the emergence of HIV, its history and the current state of the HIV/AIDS pandemic. And finally, we will explore some of the work that is being done in the search for a preventative vaccine and cure for HIV.

Ready to begin? Let’s get started.

The origin of HIV

HIV is a relatively recent addition to the history of mankind. Nevertheless, the HIV/AIDS pandemic has already caused almost 35 million deaths worldwide ever since it began in the 1980s.

But how did this unique disease suddenly emerge? How did HIV, which was only identified in 1983, even come to infect humans?

Despite being caused by completely different viruses, Ebola, rabies, yellow fever and COVID-19 all have something in common with HIV/AIDS – they are all zoonotic diseases (or zoonoses). This means that they can be transmitted from animals to humans.

Both HIV-1 and HIV-2 began to infect humans as a result of numerous cross-species transmission events of SIV (simian immunodeficiency virus; another type of lentivirus) from primates.

A cross-species transmission event, also called a zoonotic event, is when a pathogen jumps from an animal to humans. Whilst most of these transmissions fail to cause disease in humans, as our immune system can fight off SIV, the virus can occasionally evolve to overcome human defences and thereby infect humans in a ‘productive’ manner and become HIV. More specifically, during a ‘productive’ infection, the virus would infect a cell, complete its lifecycle and release new virion particles. As a result, it spreads between individuals very easily.

The first clues showcasing the link between SIV and HIV came about when researchers started looking at the ‘phylogenetic relationship’ between them. Phylogenetic relationships reflect the evolutionary history shared by organisms (viruses in this case). And especially for viruses, their phylogenetic relationship is often studied by comparing genetic sequences. Different primate species carry different SIV strains, so comparing them to HIV-1 and HIV-2 made it possible for scientists to determine the precise zoonotic origin of AIDS.

Furthermore, the different epidemiological histories (for example, the varying prevalence and locations where they are found) and pathogenicity of HIV-1 and HIV-2, including their subgroups, suggests that they were a result of multiple independent cross-species transmission events (illustrated in Figure 1).

HIV-1 groups M and N are most closely related to the SIV that comes from chimpanzees (SIVcpz), so we can assume that these groups emerged following the independent transmissions of SIVcpz from chimpanzees to humans. Interestingly, we now know that SIVcpz arose in chimpanzees when they were co-infected with SIV from red-capped mangabeys and greater spot-nosed monkeys, which they feed on. The SIV strains from these monkey species then recombined to form SIVcpz.

Meanwhile, the SIV in western lowland gorillas (SIVgor), which itself came from SIVcpz, is the origin of HIV-1 group P. In contrast, HIV-1 group O is known to have originated from SIVcpz or SIVgor, but it has not yet been confirmed exactly which one. On the other hand, HIV-2 is most closely related to SIV from sooty mangabeys (SIVsmm).

Figure 1: Cross-species transmissions of SIV (simian immunodeficiency virus) from various primates to humans gave rise to different HIV strains. For example, transmission of SIVcpz from chimpanzees to humans resulted in the generation of HIV-1 groups M and N. Besides that, HIV-1 group O originated from either SIVcpz or SIVgor; which one exactly has yet to been confirmed. The suffixes following SIV indicate which primate the virus is from – rcm: red-capped mangabey; gsn: greater spot-nosed monkey; cpz: chimpanzee; gor: western lowland gorillas; smm: sooty mangabey. Figure created using BioRender.

So, how did SIV cross the species barrier from great apes to humans?

The most widely accepted explanation is The Hunter Theory. It states that when chimpanzees were hunted and eaten, blood infected with SIVcpz was able to enter wounds of the human hunters. Following a transmission event, each of which gave rise to a different HIV-1 group, the virus adapted in different ways to its new host species.

These variations in adaptation meant that HIV-1 group M, the pandemic strain, acquired the greatest replicative and transmission fitness (i.e. it is the best variant at replicating in cells and spreading between individuals) when compared to other groups. This also explains why it is the most prevalent HIV with the largest geographical range. In contrast, the crossover giving rise to HIV-2 is thought to have occurred in a similar manner to that described by The Hunter Theory – hunting and killing sooty mangabeys as bushmeat allowed SIVsmm to infect humans, adapt and become HIV-2. HIV-2 groups A and B are much more prevalent than Groups C-H, in which like HIV-1, this can be explained by the virus adapting in numerous ways following each transmission event.

Edward Hooper had his own theory about the origin of the HIV pandemic too, but it was quickly dismissed as it was completely contradicted by genetic, epidemiological and circumstantial evidence.

During the 1950s, the oral polio vaccine (OPV) was tested in Congo, having been grown in macaque monkey tissue cultures. Hooper claimed that the vaccine had been grown in kidney cells from local SIV-infected chimpanzees, meaning the contaminated vaccine would infect humans with SIVcpz (eventually becoming HIV-1). However, we know that chimpanzee cells were not used, and that the SIV strain in areas close to the vaccination centres differ greatly in terms of genetics when compared to HIV. Therefore, it could not be the source. Moreover, the researchers knew that the SIV transmission events giving rise to the pandemic occurred way before the vaccination programmes began – thereby disproving Hooper’s theory.

The history of the pandemic

HIV only emerged in humans around one century ago, with the first cases officially reported in 1981. However, by 1999, AIDS has become the leading infectious disease killer and the fourth leading cause of death worldwide.

During one of the worst pandemics in human history, the global scientific community was faced with the massive challenge of identifying and understanding a new pathogen, as well as developing tests and treatments to prevent further deaths. Looking at some of the landmark events in the history of the pandemic, we can tell the story of how it began, developed and progressed to its current state.

The emergence of HIV and its initial spread

1920: (Kinshasa, Democratic Republic of Congo) The first cross-species transmission of SIV, which gave rise to HIV-1, is predicted to have taken place. This prediction is based on molecular, phylogenetic and demographic data. For example, all HIV-1 group M subtypes are present in Kinshasa, with loads of the first AIDS cases were reported here. Once HIV had emerged, population growth, an expansive transport network and the thriving sex trade were key factors presumed to have facilitated its spread from Kinshasa.

1937: HIV-1 had reached Brazzaville, a city 120km from Kinshasa.

1960s: HIV-1 group M had reached Haiti.

1970: HIV-1 arrived in America, although it wasn’t recognised here until the 1980s. Once the virus had reached America, it spread rapidly across the globe by international travel.

The pandemic begins…

June 1981: Five young, and otherwise healthy, homosexual men are reported to have Pneumocystic pneumonia in the United States, despite this fungus only being harmful to those with compromised immune systems. Around the same time, multiple cases of Kaposi’s sarcoma were reported in young, gay men. This type of cancer, caused by HHV-8 (human herpesvirus-8), had also only been known previously to infect immunocompromised individuals and is characterised by multiple purple skin lesions. We now know that both of these were opportunistic infections, meaning that they were able to cause serious disease in these men due to their HIV infection.

31st December 1981: In the United States, 337 cases of the new, severe and still unidentified immunodeficiency disease had been reported, with 130 people already dead.

May 1982: The disease appeared to mainly be affecting gay men, so it became known as GRID (gay-related immune deficiency).

July 1982: The United States Centre for Disease Control (CDC) reported haemophilia patients with immunodeficiency despite not having any other risk factors associated with the disease. Fast forwarding to today, we now know that these haemophiliacs contracted the disease via HIV-contaminated blood products.

September 1982: The CDC first uses the term “AIDS” to describe the disease.

End of 1982: HIV-1 had reached Brazil, Australia and many European countries.

1983: In the Pasteur Institute in France, a new retrovirus called LAV (lymphadenopathy-associated virus) was isolated and thought to be the cause of AIDS.

1984: Scientists in the National Cancer Institute in America isolated HTLV-III (human T- cell lymphotropic virus type III), which they said is the cause of AIDS and claimed that a vaccine can be developed within two years. Though in fact, LAV and HTLV-III were actually both HIV-1.

May 1986: The virus which causes AIDS is now named as HIV-1 by the International Committee on the Taxonomy of Viruses (ICTV).

July 1986: HIV-2 was first isolated in West Africa.

Controlling HIV

As scientists got a better understanding of HIV-1, they quickly needed to identify and develop measures to control the spread of this virus and limit any HIV-associated deaths.

In general, there are four main control measures, as illustrated in Figure 2.

Figure 2: Measures taken to control the spread of HIV. Unfortunately, a vaccination or cure for HIV is not yet available. ‘PReP’ stands for pre-exposure prophylaxis while ‘PEP’ represents post-exposure prophylaxis.

Avoiding exposure

Education programmes, which target high-risk individuals and ‘hot spots’ where HIV prevalence is at its highest, help to minimise exposure to the virus. For example, the ABC approach (“Abstinence, Be faithful, Use a Condom) in sub-Saharan Africa was implemented in response to the epidemic there, In addition to that, behavioural approaches have also been taken, such as distributing condoms and providing clean needles to drug users.

Detection and diagnosis

‘Detection and diagnosis’ are another set of essential steps required to control the spread of HIV. The first blood test for HIV was introduced in 1985, once the causative virus had been isolated, and has allowed blood banks to test donations for the virus. As a result, this prevented the transmission of HIV to recipients (such as haemophiliacs who rely on regular blood transfusions).

When assessing diagnostic tests, such as those used to identify HIV-positive individuals, the terms sensitivity and specificity are frequently used:

Sensitivity: The ability of a test to correctly detect people with the disease (‘true positives’). A test with 100% sensitivity will correctly identify all individuals with the disease. The lower the sensitivity, the more ‘false negative’ results are returned.

Specificity: The ability to correctly identify people without the disease (‘true negatives’). The lower the specificity, the more ‘false positive results are returned.

Tests are ideally highly sensitive and specific, but this often isn’t the case.

In reality, higher sensitivity generally means lower specificity. and vice versa. Therefore, patients who test positive with a high sensitivity/low specificity test are then subjected to a second low sensitivity/higher specificity test. This ensures that anyone incorrectly identified as positive for the disease initially will be correctly recognised as negative by the second test (i.e. it reduces the number of false positives). The overall accuracy of diagnosis is subsequently increased.

The first HIV test was an ELISA (enzyme-linked immunosorbent assay). This detects the presence of antibodies specific to an HIV antigen (typically a protein) in an individual’s blood. In fact, this is one of the main tests used in labs to check if samples are positive for SARS-CoV2 (COVID-19).

The ELISA is highly sensitive: this is useful for detecting any HIV-contaminated blood. However, around 1.5% of results are ‘false-positives’, meaning it has a relatively low specificity. This low specificity is because it can accidentally detect antibodies produced in response other diseases.

Therefore, positive results are confirmed with a second, highly specific test, which is the Western blot assay. This assay detects the presence of antibodies specific to a range of HIV antigens, rather than just one (e.g. the ELISA).

A newer type of test, known as a fourth-generation test, detect antibodies and antigens. It gives results much sooner than antibody-only tests, as antibodies aren’t produced until at least six weeks after initial infection. As fourth-generation tests are less likely to miss HIV-positive patients (i.e. fewer false negatives), they are highly sensitive. Furthermore, another available test called PCR (polymerase chain reaction) is a qualitative test, meaning that it measures an individual’s viral load by measuring the amount of HIV-related genetic material that is present in their blood.


Once someone has been confirmed to be HIV-positive, chemotherapy (drugs) can be used to reduce and maintain their viral load at an ‘undetectable’ level (i.e. HIV can’t be detected by tests). This is achieved by preventing HIV replication and infection of new host cells (Figure 3). As a result, the CD4 cell count can be restored and thereby preventing immune deficiency, progression to AIDS (when the CD4 count is <200 cells/mm3) and infection by opportunistic pathogens.

These drugs, known as antiretrovirals (because HIV is a retrovirus), allow people with HIV to live almost as long as those without the virus and also stop them infecting individuals without HIV. However, whilst antiretroviral drugs are capable of suppressing the symptoms of HIV, they cannot cure it (i.e. eradicate the virus completely). This is due to their inability to clear the latent HIV reservoir.

As discussed in Part 1, HIV can remain dormant and hidden in latently infected cells as a provirus that is ‘replication-competent’. This means that if antiretroviral therapy is stopped, the provirus will be expressed (i.e. transcribed and translated) and new virion particles will be produced.

Figure 3: The graph shows that as soon as HAART (highly active antiretroviral therapy) begins, the viral load (measured by the number of copies of HIV RNA within per mL of blood) rapidly decreases to undetectable (<50 RNA copies/mL). On the other hand, CD4 cell count (i.e. the number of CD4 cells per mm3 of blood) increases and eventually returns to normal levels (>500 cells/mm3). This figure was adapted from HIV i-base (2019)’s “HIV after starting ART".

The first antiretroviral drug, AZT (azidothymidine), was made available in 1987. However, resistance to this drug developed quickly (see Figure 4 to help you visualise how this happened). This is because HIV has an RNA genome, meaning it has a very high mutation rate due to RNA polymerase’s lack of proofreading (unlike DNA polymerase, which replicates DNA). To prevent HIV from becoming resistant to antiretroviral drugs, triple drug treatment is used, as supposed to monotherapy (where a single drug is administered). So, if resistance to one drug is developed, the mutant virus will still be killed by the other drugs. This treatment is known as HAART (highly active antiretroviral therapy).

Figure 4: Schematic showing how HIV developed resistance to the antiretroviral drug, AZT. It begins with (i) the initial wild type virus (red) not being resistant to AZT. When the host RNA polymerase is used for replicating the viral RNA genome, it regularly introduces (ii) mutations. One of these random mutations conferred resistance to the drug AZT. This provided the mutant, resistant virus (blue) with a (iii) fitness advantage as it wasn’t killed, whilst the wild type virus would be eliminated. The mutation then (iv) spreads and the resistant HIV strain is transmitted between individuals.

There are six different classes of drugs, summarised in Figure 7, which can be used:

1. Nucleoside reverse transcriptase inhibitors (NRTIs; See Figure 5)

NRTIs competitively inhibit the reverse transcriptase enzyme. The reverse transcriptase active site normally binds to deoxyribonucleotides (i.e. the building blocks of DNA) to form phosphodiester bonds and thereby synthesise DNA from an RNA template.

The competitive inhibitors are ‘chain terminators’ – they are a similar shape to normal nucleotides, so they fit into the active site. But once they are incorporated, the DNA chain cannot be elongated any further as the terminator lacks the correct chemical structure to form a phosphodiester bond. In essence, AZT is an example of an NRTI, though it has side effects such as anaemia as it interferes with the host cell division.

Figure 5: (a) The reverse transcriptase’s active site binds to deoxyribonucleotides to synthesise DNA from HIV’s RNA template. (b) Nucleoside reverse transcriptase inhibitors (NRTIs) bind to reverse transcriptase’s active site and are incorporated into the growing DNA molecule. Since NRTIs are chain terminators, no nucleotides can be further added as NRTIs prevent the formation of new phosphodiester bonds. This ultimately means that DNA polymerisation (synthesis) is blocked. These figures were adapted from Viral Zone (2020)’s “Nucleoside Reverse Transcriptase Inhibitors.

2. Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

These drugs non-competitively inhibit reverse transcriptase, meaning that they bind to the enzyme away from the active site to halt its activity. Nevirapine is an example of an NNRTI.

3. Protease inhibitors

The HIV genes, gag and pol, are expressed as polyproteins that need to be cleaved by HIV’s protease before they are functional. Without this cleavage, virion particles remain immature and are unable to infect new cells. An example is the drug saquinavir.

4. Attachment inhibitors (See Figure 6)

There are various types of attachment inhibitors. One example is CCR5 antagonists (for example maraviroc)– these block the CCR5 co-receptor on CD4+ cells to prevent M-tropic HIV (the strain which uses CCR5 as a co-receptor) from entering its host cell.

Figure 6: CCR5 is a co-receptor used by the M-tropic HIV-1 strain to enter its host cell. In essence, CCR5 antagonists block the co-receptor so that the virus can’t enter CD4 cells. These antagonists are members of the antiretroviral drug class attachment inhibitors. This figure was adapted from ClinicalInfo’s ‘CCR5 antagonist’ and made using BioRender.

5. Fusion inhibitors

Fusion of the viral and host membrane is needed for HIV to insert its capsid into the cell and infect it. Fusion inhibitors therefore prevent the virus entering new cells. Enfuvirtide, an example of a fusion inhibitor, is generally used as a last resort.

6. Integrase inhibitors

Integration of HIV’s genome is an essential part of its lifecycle. Without it, no new virion particles can be produced. Integrase inhibitors, such as Raltegravir, are particularly useful as there is no equivalent enzyme in humans that could be affected by it.

Figure 7: Each class of antiretroviral drugs targets a different stage of the HIV-1 lifecycle. In addition, triple drug therapy is made up of three drugs, each from a different class. NRTIs stands for nucleoside reverse transcriptase inhibitors, whereas NNRTIs stands for non-nucleoside reverse transcriptase inhibitors. This figure was adapted from Clinical Pharmacology in HIV Therapy (2019) and made using BioRender.

HAART is undoubtedly invaluable in the fight against HIV. As a result of it, 1.6 million deaths were averted in 2016.

However, there are some significant limitations to it. Firstly, HAART costs $10,000 dollars a year. In some poorer countries in Africa and Asia, where HIV incidence is highest, the entire health budget is restricted to $10 a year per person. Because of this, only 68% of HIV-positive adults and 53% of infected children were on HAART in 2019.

Figure 8 shows that HIV/AIDS is responsible for 28% of deaths in South Africa compared to only 1.7% worldwide. The significant difference in the proportion of deaths due to HIV/AIDS across the globe is because developing countries generally have a higher HIV prevalence but less money available for HAART. Not to mention, the drugs must be taken for life as they don’t eradicate the virus. If therapy stops, the viral load will increase, and the patient becomes infectious and symptomatic. Also, triple therapy has only been used since 1994, so we don’t know the long-term consequences of taking the drugs for life. Besides that, the life expectancy of those on HAART is still around 10 years shorter than their healthy counterparts.

Figure 8: In 2017, HIV/AIDS caused 1.7% of the deaths globally. This map illustrates the huge variation in the proportion of deaths caused by HIV/AIDS across the world. For example, HIV/AIDS was responsible for 28% of deaths in South Africa and Botswana, but less than 0.1% in most European countries. This figure was adapted from Our World In Data (2019)’s “HIV/AIDS".


The final method of controlling HIV is prevention. Given the limitations of HAART, it is best to stop people from getting infected in the first place. Therefore, ‘avoiding exposure’ and ‘preventing infection’ should be prioritised, with chemotherapy as a back-up if all else fails.

PReP (pre-exposure prohylaxis) and PEP (post-exposure prophylaxis) are anti-retroviral drugs taken by HIV-negative people. PReP is used by people who are at risk of being exposed to HIV, and it almost always completely eliminates the chances of getting infected. Meanwhile, PEP is taken after exposure to reduce the chances of HIV infection.

In general, vaccines are optimal when it comes to controlling pandemics as they prevent infection and, in the case of some diseases, can lead to eradication.

Vaccines provide active, artificial immunity. Active immunity is a result of a person’s own immune system generating a response when exposed to an antigen, and artificial immunity indicates that exposure to the antigen occurred via vaccination rather than natural infection. When exposed to an antigen (whether it is live, attenuated or killed), specific B and T lymphocytes which are complementary to the antigen are activated and differentiate into different cell types, such as B plasma cells and cytotoxic (killer) T cells. When the pathogen has been cleared, most of these cells die, but some remain in circulation in case the same pathogen infects again. These ‘memory’ cells provide long-term immunological memory and enable a faster, stronger attack to be carried out in future when the same pathogen attacks our body.

The benefits of vaccination are clear, yet there is still no successful, preventative HIV vaccine available, even though over 30 candidate vaccines have been tried. There are a few main reasons why efforts to obtain a vaccine have failed:

1. The ‘correlate of preventative immunity to HIV’ is unknown.

This means that we don’t know the exact type of immune memory that is needed to prevent infection. It could be specific antibodies, or it might be T cells instead. The reason for this is that no one has natural immunity to HIV; unlike other viral diseases like measles, no one naturally recovers from HIV and develops an immunological memory to prevent reinfection. It is therefore impossible to study natural immunity and determine what immunological protection a vaccine would need to generate.

2. Lack of a small animal model to work on.

These animal models are essential for testing how safe and effective a vaccine may be on humans.

3. HIV’s genetic variation

There is a great level of HIV diversity worldwide due to the virus’s high mutation rate. For example, HIV envelope antigens vary in different strains around the world. Although we are aware of this variation, we don’t know what its impact on immune protection is – would different vaccines be needed for each HIV-1 subtype?

Because 95% of new infections are in developing countries, pharmaceutical interest in an HIV vaccine is relatively limited. However, a recent trial, known as the Thai Trial’ (because it was carried out in Thailand), found the first vaccine which conferred some protection against HIV. It was one of the first candidate HIV vaccines that reached the Phase III trials and involved over 16,000 volunteers. Generally, clinical trials are studies to evaluate efficacy and safety of therapies on humans and are divided into four stages (Figure 9).

The trial was testing the ‘prime-boost’ vaccination strategy, a regimen which consisted of two vaccine candidates:

i) Prime: The first vaccine used a canarypox viral vector which was genetically engineered to carry the HIV genes gag, pol and env. A viral vector is an attenuated virus (meaning that it doesn’t cause disease) used in molecular biology to deliver specific genes. This vaccine generates a T-cell mediated response.

ii) Boost: The second vaccine was made of genetically engineered gp120 (one of HIV’s envelope proteins) and generates an antibody-mediated immune response.

Using the prime and boost vaccines individually had not been successful in conferring protection against HIV in previous trials. However, the Thai Trial found that the prime-boost vaccination strategy resulted in 31% fewer HIV infections in those who received the vaccine when compared to those who received the placebo. Although it conferred some protection, the 31% efficacy was not high enough to warrant its use for a disease as serious as HIV.

Another limitation of the vaccination strategy is that it was based on the HIV-1 group M subtype E, which is not found in Africa. Also, the regimen requires four separate visits for six injections. The trial did, however, provide lots of detailed data for use in future vaccine research. For example, it showed that it was the boost vaccine’s antibody response, and not the prime T-cell response, which was responsible for the vaccine’s efficacy.

Figure 9: The four stages of clinical trials which comes along after conducting preclinical research in labs. Clinical trials are essential for determining the safety, potential side effects and efficacy of vaccines and medicines. As the trial progresses, the number of participants increases. For phase III and IV trials of HIV vaccines, the higher the HIV incidence in the population being studied, fewer people are required. For this reason, many HIV vaccine trials are conducted in developing countries, like Thailand and South Africa. This figure was adapted from Novartis’s “Clinical trials.

A cure for HIV?

We have covered HIV prevention (vaccines, PReP, etc.) and therapeutic (HAART) strategies. However, it is clear that there lots of challenges in the search for a vaccine and disadvantages to the life-long HAART. Therefore, finding a way to cure patients of HIV (meaning to eradicate the virus completely from their body) would be invaluable in the fight against HIV.

Such eradication is difficult due to the latent reservoir established by the virus, which can persist for decades. So how would we go about curing HIV?

There are a range of avenues being explored in an attempt to answer this question, as well as many future options yet to be discovered. For now, we will discuss two approaches being researched at present.

Gene therapy

Gene therapy involves delivering foreign DNA into a patient’s cells to cure them of a disease. In the context of HIV, the aim is to make cells resistant to HIV infection or clear the virus from infected cells. This has been performed successfully twice; first in the Berlin Patient’, and second in the London Patient’.

The HIV-positive Berlin patient was due to receive a standard stem cell transplant to treat his leukaemia, but the procedure was unusual as the bone marrow donor was chosen due to a mutation they had which confers HIV resistance. The mutation is a deletion of 32 base pairs from the CCR5 gene (therefore called CCR5D32). The resulting shortened protein can’t function as a co-receptor, so HIV can’t bind and enter the host cell. 1% of Caucasians are homozygous for this mutation (they have 2 copies of it) and are resistant to M-tropic HIV, whilst the disease progresses slower in the 10% who are heterozygous (have one copy). The CCR5D32 stem cells (precursors to white blood cells) were transplanted into the patient, eventually becoming HIV-resistant white blood cells.

The same was done in the London patient, and both eventually came off HAART with the virus yet to return.

The success of these patients’ treatment is significant as it shows the huge potential for gene therapy as a cure for HIV. However, stem cell transplants pose lots of risks and requires aggressive chemotherapy beforehand, which is far worse than the negatives of life-long HAART. Not only is this treatment not a realistic option for wide-spread use, but gene therapy is relatively new, so we still aren’t sure of its long-term effects. Also, T-tropic HIV uses CXCR4 as a co-receptor instead of CCR5, so patients remain susceptible to infection by this strain even after the transplant.

Another approach based on this principle of introducing the CCR5D32 mutation into immune cells was carried out recently in China. Eggs from an HIV-negative mother and sperm from an HIV-positive father were extracted, then CRISPR gene editing was carried out on the resulting embryos to disrupt the CCR5 gene. The woman gave birth to genetically edited twins who were HIV-resistant, like Berlin and London patients. The experiment was globally condemned as the implantation of gene edited embryos is widely considered to be unethical and dangerous. Furthermore, it has since been found the absence of the CCR5 receptor confers increased susceptibility other infections, such as the West Nile Virus.


Immunotherapy is defined as a treatment that stimulates the patient’s immune response to fight against diseases and is commonly used as a cancer treatment.

One example of immunotherapy is CAR-T cells. This involves removing the patient’s own T cells and re-programming them to express Chimeric Antigen Receptors (CAR) specific to HIV-infected cells. The result is CAR-T cells are capable of detecting and killing HIV-infected cells, thereby clearing the HIV latent reservoir. Further modifications can be made to these cells to make them resistant to HIV infection, for example, by disrupting the CCR5 gene to prevent HIV entry.

Why should we study HIV?

Part 1 and Part 2 of the HIV series should have hopefully taught you about the virus and the nature of the disease it causes. You will also know more about the history of the devastating HIV/AIDS pandemic and how the virus came to infect humans. Finally, we have had a brief look at some of the essential research being carried out by scientists as part of the effort to fight HIV.

Why is all of this important?

Although we have made a lot of progress since HIV first emerged, and treatment for the virus mean being diagnosed as HIV-xpositive is no longer a ‘death sentence’, there is still lots more to be done.

The current state of the pandemic speaks for itself. In 2019, 1.7 million people were diagnosed with HIV, with just over half of them receiving antiretroviral therapy. Huge numbers of people have died already as a result of the virus, and lots more continue to die every day. Furthermore, the pandemic disproportionately affects poorer countries, many of which are plagued with a vast range of other infectious diseases.

It is critical that we understand as much as we can about the virus so that treatments can be improved and eventually a vaccine and cure can be developed. Understanding the HIV/AIDS pandemic is also essential as it allows us to learn from the mistakes made, and in doing so, better prepare ourselves for present and future pandemics.

Author: Ambar Khan, BSc Biological Sciences

Disclaimer: All figures created using BioRender are intended solely for educational purposes and not for profit.


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