AIDS: where have we got to?

Submitted by Matthew on 3 October, 2012 - 1:34

Just over 30 years ago, the disease soon to be called AIDS (acquired immunodeficiency disorder), but then termed GRID (gay-related immune deficiency), was first reported in the US. Sufferers predominantly came from the “four H’s”, homosexual men, heroin users, haemophiliacs and, curiously, Haitians.

Many had unusual infections, including a type of pneumonia, and a rare cancer (Kaposi’s sarcoma). Death rates were high, the cause being infections that the body was unable to fight, due to the loss of a vital component of the immune system, CD4+T lymphocytes or T helper cells.

Quite soon, it was found to be caused by infection with a virus, dubbed human immunodeficiency virus (HIV). The virus was not itself directly harmful but caused the T-cell count to fall dangerously low, leaving the body susceptible to infections that it could normally easily overcome. Such “opportunistic” infections typically affect people with weakened immune systems. The appearance of various tumours confirmed the role of the immune system in suppressing some cancers, now known to be caused by viruses.

It was transmitted through body fluids exchanged in sexual activities involving men (both homo- and heterosexual), sharing needles (intravenous drug users or patients in some medical settings), transfusion of blood or blood products from donors with HIV infection, and from mother to child during pregnancy, birth or breast-feeding.

AIDS-related bacterial infections could be treated with antibiotics, though antibiotic-resistant strains rapidly became a serious problem.

However, viruses can’t be treated with antibiotics ( a fact not realised by many people with ‘flu or colds). Anti-viral drugs are less available and less successful. And, as we have seen, the other line of defence, the immune system, had been breached. Furthermore, HIV, as a “retrovirus” (see info box) could lie dormant for up to 20 years by incorporating a copy of its genetic material in the DNA of the “host”.

Transmission of HIV is high in the early stages, before an immune response reduces the levels of virus particles in the blood, and later, when the disease re-emerges and serious illness starts to develop. A small percentage, perhaps 5%, of people, have a delayed response to HIV infection or indeed no response – they have partial or even complete resistance to HIV.

In the absence of a reliable cure (so far), prevention has been the main medical focus. Protected sex reduces transmission to almost zero; proper screening of blood products protects haemophiliacs and recipients of blood transfusions; provision of clean needles protects intra-venous drug users and people having medical injections; Caesarean delivery and formula milk protects babies.

Several treatments have been developed and have greatly increased the life expectancy of HIV-positive people able to receive these. There are several anti-retroviral drugs, which specifically target the enzyme reverse transcriptase, produced and used by HIV but, crucially, not by human cells.

The first of these, AZT (azidothymidine or Zidovudine), was synthesised as a potential anti-cancer drug in 1964 by chemist Jerome Horwitz, who has just died, aged 93 (see below). Unfortunately, AZT has serious side-effects, damaging bone marrow and causing anaemia. HIV was also able to develop resistance to it so that mutant reverse transcriptase no longer used it. It is now used in moderation and in combination with other drugs.

HAART (high active anti-retroviral therapy) is the current treatment of choice, slowing the progress of the disease greatly.

Typical combinations of drugs include reverse transcriptase inhibitors, AZT and compounds like it, or, later on, protease inhibitors (these make it difficult for the virus to assemble itself for release to infect another cell). Side effects are fewer and costs are lower, though this is still an issue in poorer countries and where people have to pay for medication up front.

Alternative therapies used include vitamin supplements which only seem to help where the diet is deficient. Herbal medicines have not been shown to be effective.

Some virus infections (such as smallpox and polio) can be prevented by vaccination. So far, attempts to develop an effective vaccine against HIV have been thwarted by its fast rate of mutation. There are two ways a vaccine could be given: before infection to large numbers of the at-risk population to prevent them catching HIV; or after the infection with the aim of boosting the patient’s immune response. A field trial involving 16,000 Thai volunteers recently reported a modest success, with the risk of contracting HIV being reduced by about one-third.

One leukaemia sufferer with HIV was given stem cells with resistance to HIV. This seems to have resulted in either a cure or a long-term suppression of the infection. This is still experimental because of the risks of such transplants and the lack of suitable donors. Two more recipients of ordinary stem cell transplants seem to have benefited also and have no HIV in their blood.

Abzymes (antibody enzymes) have been developed to recognise the protein on the surface of the HIV particles that binds to CD4 cells, attach to it and destroy it by enzyme action. This would prevent the virus sticking to CD4 cells, preparatory to entering it and taking it over. Being an enzyme, a type of catalyst, the abzyme would then detach and be free to attack more HIV particles.

Another possible line against HIV involves preventing HIV incorporating its DNA into host’s DNA. The virus would then be susceptible to attack with anti-retrovirals.

And yet another experimental technique involves giving anti-retroviral therapy to patients soon after infection and maintaining this for three years.

A group of 14 patients still had very low levels of HIV six years after stopping all medication. Though HIV-positive, they seem effectively cured.

What is a retrovirus?

Most viruses have a genome of DNA which codes for the proteins they need to replicate. These include genes for coat proteins, which self-assemble into a virus particle and enclose a copy of the genome.

Viruses use the host cell’s own machinery to make messenger RNA (mRNA) from the genes, and proteins from the mRNA. They are obligate parasites which can do nothing by themselves.

Some viruses have their genetic material as RNA (which can be directly translated into proteins by the host cell). One gene codes for an enzyme, reverse transcriptase, which translates the RNA genome into DNA. This can be incorporated into the host cell’s DNA and lie dormant for up to 20 years. Significantly, RNA is less stable than DNA so mutations are more frequent, leading to faster evolution.

Sometimes something goes wrong and the genetic material becomes permanently incorporated into the host’s DNA. Some of the genes are harmful to the host while others are useful. Incredibly, it has recently been shown that about 8% of our (and other organisms’) DNA is of viral origin, including the gene that causes the placenta to attach to the wall of the mammalian uterus!

Since DNA is normally translated into mRNA and not the other way round, viruses which do this are called retroviruses.

AIDS villains

Government failures

Margaret Thatcher’s Conservative government and the NHS failed to ban unsafe blood products being imported from the US, where blood was bought from intravenous drug users. This was known in 1983. 1,200 haemophiliacs were infected with HIV (900 died). Lord Robert Winston called this “the worst treatment disaster in the history of the NHS”. Subsequent Labour and Con-Dem governments have refused adequate compensation.

AIDS denialists

Lynn Margulis, was an eminent scientist who showed that mitochondria, the powerhouses in all living cells, are descended from bacteria. However, she persisted in the misguided and insulting theory that AIDS was caused by tertiary syphilis and not HIV. (She was also a “9/11 Truth Seeker”!)

Peter Duesberg, an eminent cancer researcher, proposed that HIV was harmless and that AIDS was caused by long-term use of recreational drugs (news to the haemophiliacs and babies that get AIDS) or by taking anti-retroviral drugs (for AIDS!). He was an adviser to President Thabo Mbeki, under whose “leadership” anti-retroviral drugs were not provided in a timely fashion. This has caused over 300,000 preventable AIDS deaths in South Africa.

Duesberg once offered to infect himself with HIV to prove his theory but, sadly, did not do so.

Quack cures

Manto Tshabalala-Msimang, the South African Health Minister under Thabo Mbeki, recommended treating AIDS with alcoholic beverages, garlic and beetroot.

Matthias Rust, a German vitamin salesman, recommended that South African AIDS sufferers stop taking anti-retrovirals and take high doses of vitamins.

Some non-mainstream churches, including the Christian Scientists, claim that prayer will heal AIDS sufferers and that they therefore need not take medication.

Conspiracy theorists

A theory that HIV was genetically engineered by US scientists as a form of biological warfare seems to have arisen in the then Eastern Bloc.

Gerry Healy’s Workers Revolutionary Party published a sympathetic treatment of the “theory” that AIDS was an “imperialist plot” in Workers Press.

Who was Dr Jerome Horwitz?

Jerome Horwitz designed a new class of compounds, modified nucleotides (the building blocks of DNA), which would disrupt rapidly multiplying cancer cells by wrecking production of new DNA.

Unfortunately, they didn’t work and he forgot about them, not even taking out a patent. In 1984, when HIV was identified, Burroughs Wellcome started screening its archive of compounds and found that AZT was able to do to viruses what Horwitz had originally hoped it would do to cancer cells – fool reverse transcriptase into incorporating AZT into the growing DNA strand, instead of the proper nucleotide, thymidine. The DNA could grow no longer and the virus could not multiply.

But the new therapy cost $10000 a year, with sales of $400million for BW in 1992. Horwitz received nothing.

However, his work was valuable and shows yet again that research unsuccessful for its stated goal may have great worth in unsuspected areas.