Brief History

Project AMAS | A Multidisciplinary Approach to AIDS

Brief History

Chronological summary of the most significant facts related to vih/aids from 1999.

Information and how it arrives is the key to understanding HIV/AIDS.

Misinformation or very slanted perspectives make us anguish or have false hopes. We must be cautious in the moment of listening to or seeing information about HIV/AIDS, especially through communcation media (TV, newspapers, magazines, film), but also when we go to the doctor, to school or even between friends. The informaton you find here at amas.org will hopefully be varied and correct and up-to-date. Treatment documents, here like everywhere, are temporary. The dates are very important and they should always be contrasted with other information in order to be able to make discreet and rational decisions. This is the year 2000, and these documents reflect our time. Every 6 months to 1 year, one should expect updates of a serious nature that make you rethink what you have learned up until now, or at least add a little bit of knowledge to what you already have.

HIV/AIDS, its consequences and how to treat it, evolve rapidly. What was absolutely valid just one year ago may now be close to meaningless. Keep that in mind.

In a fairly short period of time, there can appear new discoveries and new drugs and the great majority of this web page will be obsolete. Check the dates! Every day there are new discoveries in immunology and virology closely related to treatment of HIV. It is up to you to keep yourself abreast of what is new in the field. We will try to help. It means a lot of work for you, and this web page will try to make as much as possible as comprehensible as possible in as little time as possible. We will touch especially but not only themes related to HIV treatments and nursing, from a strategic as well as a human point of view.

Do not ever be too satisfied with what you find and/or decide you know. Look for more/other information, other ponts of view. HIV is in a constant state of flux and so we have a large and growing and frequently changing list of links to help you get to the documents that are more relevant so you can contrast what you have found, validate or repudiate what you know.

An unknown ilness was striking a series of men and a limited number of women in the summer of 1981. It was given an epidemiological name, related to the people who got it, but not necessarily to how they got it, or really what it was. GRID was the deadly disease that stood for Gay related ImmunoDisease. A group of French doctors and almost simultaneously an American group found the virus that caused this disease some four years later. The virus was first known as HLTV. Over the following couple of years, GRID became AIDS and HLTV became HIV. It was almost always deadly and very rapid. At first, they were one and the same, the virus and the disease. Only with the appearance of the antibody test could it be seen that some people had the virus without being mortally ill in the same moment.

Since then, 1981, some 40 million people have contracted the disease, with more than half dying of it around the world. For the past few years, we have seen that the heaviest toll of this disease happens in poor, underdeveloped nations with almost no health care infrastructure, particularly Africa, Asia and South America. Although it was first identified in the US and has hit hard in Europe, the US and Australia, the heaviest toll is happening now in other parts of the world. More than 17.000 new HIV infections happen daily. The incidence in the west is comparitively low, although it is estimated that nearly a million people in Europe have HIV and the same in the USA. A special note about Eastern Europe: it is becoming more and more clear that Eastern Europe and especially the former Soviet Union states have an out-of-control epidemic that will equal anything happening in the rest of the world. Official transmission rates are some 10.000 cases per month in the exSoviet republics, with "real" transmission estimated to be ten times higher. And access to treatment issues are similar to those in any other developing nation, virtually impossible, including for opportunistic infections.

Up until now there is no cure or vaccine for HIV. HIV is forever. But in the past few years in the west, treatments have developed to such an extent that HIV is controlled in many cases for many years. The use of treatments has been studied and proven in many many protocols. The levels now found in the blood of an infected person can be brought down from nearly one million copies per mililiter to less than 20.

This reduction in viral load as it is called may in fact help fend off the destruction of the immune system which is the basis of HIV progression, opportunistic infections and death. In the past 20 years, much has been discovered biologically, molecularly and pathogenically about HIV. Below is a brief and not complete step by step story of HIV/AIDS and antiretroviral therapy.

1981

The first cases are published. It is known as GRID.

1983

Montaigner (France) y Gallo (USA) identify HIV (HLTV) as the virus that causes GRID.

1986

HIV is beleived to be latent for many years in the human body.

Antibody tests areintroduced to measure the antibodies to the virus in the blood.

Llistes per a BW002 (monoteràpia d’AZT)

1987

AZT is the first approved antiretroviral agent (Nucleoside analog reverse transcriptase inhibitor)

The CD4 count is recognised as an indicator of HIV progression

The results of BW002 are published

ACT UP is formed in New York under the banner "Informatio and Access".

1988

First report of ddC monotherapy

ACT UP is in 130 cities around the world, and does an Action in Wall Street Market on the Trading Flloor. The next day, prices drop 30%.

1989

Ho, Combs and others suggest that the quantity of free virus in the blood is higher than previously estimated.

1990

Sequential antiretroviral therapy is introduced.

Early use of AZT is advised to control HIV infection.

First report from ACTG019 (AZT monotherapy)

1991

It is seen that the lymphoid system is a great reservoir of HIV.

1992

Confidence in antiretroviral therapy shrinks after disappointing results of some studies.

A small minority questions the theory that HIV causes AIDS.

Both ddI and ddC are approved.

ACT UP coordinates one of its great actions in Bethesda (at NIAID) to fight for the changing of one of the bedrocks of drug approval at the FDA, and gets conditional approval faster.

1993

Pantaleo, Embreston and others call attention to the fact that HIV replicates hugely during the asymptomatic phase.

PCR and in situ hybridization make it possible to see the lymphoid architecture.

New, more sensitive techniques than PCR are introduced to meaure the viral RNA.

EACG020 report (AZT monotherapy).

ACT UP Paris gets a global expanded access for 3TC for some 35.000 people.
Today it is realised that Wellcome may in fact have caused widespread resistance to their drug within a matter of a few short months. 3TC with AZT lasts only a short time. At that time, it was the only possibility for these thusands of people.

1994

Ho, Shaw and others document the HIV replication dynamics.

Combination therapy is introduced.

Protease inhibitors and Non-nucleoside reverse transcriptase inhibitors begin to be tested. At first, results are disappointing, as both classes cause resistance(s) quickly.

Long-term non-progressors are defined. (LTNP)

1996

Berger, Paxton and others identify the chemokine receptors as coreceptors of HIV.

Viral load is accepted as a marker for HIV progression.

Ho and others propose in Vancouver "Hit Hard, Hit Early".

The FDA approves saquinavir, the first protease inhibitor (PI).

ACTG 175 report (AZT+ddI versus AZT+ddC versus AZT mono).

Delta report (AZT+ddI versus AZT+ddC versus AZT mono: naives vs pretreated).

NUCA 3001 and NUCB 3001 (AZT+3TC/Epivir) are published.

The INCAS (BI1046) study is released (triple combination with nevirapine, an NNRTI with two RTIs).

S’aprova saquinavir, el primer d’una nova classe, els IP.

1997

Two more effective PIs are approved as part of triple therapy - ritonavir and indinavir.

Some 10 -11 antiretroviral agents are available, with more in development.

FDA approves delavirdine.

SUSTIVA (efavirenz) is OK'd for compassionate use in the US.

The CAESAR study (AZT+lamivudine versus AZT+placebo) is published.

Triple regimen results show a serious drop in viral load to undetectable limits for extended periods of time.

ACTG 152 study (AZT versus ddI versus AZT+ddI in infants) is released.

Pilot study CHTNP 088 (ddI+hidroxiurea) is released.

1998

Combinations are more difficult and complicated, but in one year, the disease changes drastically, Morbidity and mortality drop for the first time in North America, Europe and Australia thanks to the therapies.

1999

The drop in deaths and illnesses evens out a little, but the change in progression continues unabated. More and more people in the West get infected, but less and less get ill and die.

With the approval of Efavirenz in Europe, some 14 drugs are now available to combat HIV Infection.
Also, some major Immunobased therapy trials are underway or starting, to prove the theory that HAART + Immune based therapies may be a doouble front attack (lowering the virus on one hand and supporting/sustaining the immune systyem on the other).

Side effects and the long term ability of people with access to the treatments to be able to sustain taking those treatments becomes more of a focus.
Lipodystrophy, the redistribution and possibly simultaneous loss of fat in different parts of the body, is still not defined, let alone resolved.

2000

Throughout the year, new drugs and new formulations are approved in both the US and Europe.
By the end of 2000 there is one formulation (Trizivir) with three drugs in one capsule that in many respects may make adhesion easier, although the number of pills is just one issue in how to be and stay adherent to a drug regimen.

New theories are introduced for treatment, including one from Abbott that seems to say that resistance can be overcome with more drug.
No matter how resistant one is to a drug, at some point, the amount of drug overcomes that resistance. This has to be verified in real life, and even if verified, always has to be contrasted with toxicities. One not unusual study in Barcelona shows a 60% failure rate at 6 months due to side effects.

Lipodystrophy remains important, and begins to drive the search for alternative methods of therapy, including Structured Treatment Interruptions, whereby every X period of time, a treatment is suspended for two reasons-
one, to give a pause to the patient to recuperate somewhat form side effects, and two, to try to stimulate the immune system to begin recognising HIV itself and mount a response, with treatment reinitiated as necessary. Studies are happening now.

The World AIDS Conference takes place in South Africa, and for the first time, issues of developing nations becomes the focus of attention of the whole world. (Please see the many news articles in amas.org).

2001

Throughout the year 2001, Eastern Europe registered as one of the hottest places in the world for HIV transmission, and an accompanying reticence on the part of the authorities to do anything about it.
Members of the Russian Ministry of Health have been raising the alarm at least since March of 2001, proclaiming the alarming rise in transmission and prophesising a health crisis throughout Russia. This all turned out to be true by the World AIDS Day statement by UNAIDS that showed an official figure of near 150,000 transmissions in 2001 and an estimated real figure of 1,000,000. Although the numbers are smaller in neighbouring Ukraine, the rate of transmission in the general population is now at 1% there, lower than in many African nations (where it is around 10%), but in any case, a true disaster for a health care system that is already overburdened (www.unaids.org/epidemic_update/report_dec01/index.html, then hit “Spanish”).

Treatments throughout the Newly Independent States (NIS, ex-USSR) for all intents and purposes do not exist.
In Russia, with 150,000 new HIV+ people, 500 are getting combination treatment, and of all the NIS, your best chance of getting treatment is in fact in Russia! Closer to Western Europe, countries like Poland and Hungary report a more stable maintenance both of transmission and of access to treatments, although due to the non-existence of support groups of almost any population affected by HIV, there may very well be a hidden epidemic there as well.

In countries like Romania, Bulgaria, the ex-Yugoslavias, etc, the political turmoil makes it very difficult to get a handle on the size of the problem, but one thing is clear, for those who are infected, there is little hope of getting treatment.

In Europe itself, the number of AIDS cases has levelled off, although the death rate today has maintained itself at approximately 50% of the “plague years”, and is still unacceptably high.
In one hospital in Madrid that has looked at AIDS deaths historically, there was a steadily increasing rate until 1996, then it was cut in half to approximately 20 deaths/year today (ECCATH 2001, Athens).

While AIDS and AIDS deaths has maintained stable, so has the rate of transmission of HIV, but at its peak.
Again in Spain, but reflected throughout Western Europe, HIV transmission has not dropped, which means that every day, with less and less deaths, there are more and more people living with HIV. Therefore many more people are living (or learning to live) with treatments also (again, ECCATH 2001, Athens).

New treatments

One of the first new treatments of 2001 was Lopinavir, a protease inhibitor, to be used in combination with other HIV drugs.
Lopinavir is very powerful and seems to work in a large population, but with such a powerful drug come more and more complications. Some have opted not to go toward this drug simply for the reason that with all the adverse events already existent, it does not seem to be the best way forward for many people (www.projinf.org/spanish/fs/lopinavirsp.html).

At the end of 2001, tenofovir (Viread) was approved in Europe. Tenofovir is a non-nucleotide, similar to nucleosides, but with a distinct (and hopefully important) resistance profile.
It is easy-to-take (one pill a day, of course in combination with at least two other HIV medicines), and its side effects profile still has to be determined, but at the moment does not present anything particularly frightful (www.aidsinfonet.org/428e-tenofovir.html).

Interleukin-2 is an immunotherapeutic measure. Although its side effects are very difficult in the short term, the benefits may be beneficial and long lasting.
The idea is that it can restore the amount of CD4 cells, and therefore, the level of health of one’s immune system. Logically, taking it with the more T cells the better (when they still have their memory), but it has also been shown to work in advanced people, although the side effects are harder to withstand when you are more immunodepressed. It is being studied in two large cohorts of patients – final results are not expected before 2004 (www.aidsinfonyc.org/network/simple/iltwo.html).

Atazanavir is a protease inhibitor that has been seen to have less of the laboratory markers that lead to lipodystrophy.
It has not been studied long-term, and final statements cannot be made. It may get approval sometime in 2003 (www.crha-health.ab.ca/clin/sac/Atazanavir.htm).

T20 is a drug (an entry inhibitor) due to appear in 2003.
It is very difficult to make, to use, to store and to buy (it will eventually cost what the other 3 components of the regimen cost together). It has not been used in many people yet, but the anecdotal reports are getting less and less hopeful. It seems that resistance may be quick to develop, as quick as with any drug given in a monotherapy setting (in advanced patients, whose virus may already have resistance to the other drugs). It is injected twice a day (www.aidsinfonet.org/403e-new-drugs.html#anchor101199).

Remune, an immunotherapy, was formally and finally put to rest.
As a therapeutic vaccine, it was shown not to work, and the sponsors spent a lot of energy trying to hide the official data. There are rumours that it is still being studied in Spain, although those rumours have not been confirmed (199.105.91.6/treatment/drug/ID294.asp).

Other classes are fusion inhibitors and tat inhibitors. Nothing is much beyond Phase 1 studies at the moment.
There are also early Phase studies of many other known classes. Although many of the present HIV companies are always threatening to leave the “AIDS field”, at least two new large ones will be entering in 2002.

Therapeutic Drug Monitoring has been shown to be helpful.
In many instances, people who do suffer from adverse events are simply taking too much drug, and the dose can be adjusted, so they can continue with the treatment in a more benign fashion. And those who may be taking too little (for size and or other metabolic reasons) may have their doses upped in order to maintain the therapeutic window that the drug needs to maintain itself against resistance (liv.ac.uk/Pharmacology/research_hiv.htm).

Complications and side effects – Cardiovascular side effects grew in importance, as did hepatotoxicity (www.hivandhepatitis.com).
Erectile dysfunction is now a major concern (www.eatg.org/eatn/10_05/en/indice.html). Depression may be near the top in terms of frequency (www.aidsmeds.com). All this on top of the other complications seen up till now with treatment, including lipodystrophy (www.projinform.org/fs), mitochondrial toxicity, lactic acidosis, gastrointestinal issues and neuropathies (www.thebody.com/treat).

The European Drug Agency (EMEA) opened a new office for “Orphan Medicinal Products”, those substances that do not have effect in a very large population.
These drugs therefore would probably never make a lot of money for their sponsor, so are not developed. The EMEA is trying to allow these products to be legalised with less economic input from their sponsors. Also, on this committee will be a person from the affected disease area, to give valuable perspective (pharmacos.eudra.org/F2/orphanmp/index.htm).

Spain again was forward looking in authorising a trial for the maintenance use of heroin.
One thing they would not allow (and a few Ministerial employees lost their jobs) was a trial on the importance of using marijuana as a weight control and anti-nausea tool (www.msc.es/agemed/Princip.htm). Maybe in the next century…

Spain has authorised transplants in HIV+ people.
The thing is, up until today, they have not actually done it, claiming that the waiting list is huge as one of the reasons for not putting it into practice. Another reason they say is the hesitation on the part of surgeons (www.msc.es/ont/esp/home.htm).

Now the EU is looking into Direct-to-Consumer information for drugs.
It will not be advertising like in the US, but may be a way for persons to get more information about treatments. This is still being debated regarding how and when (pharmacos.eudra.org/F2/eudralex/vol-1/pdfs-es/920028es.pdf).

2002

AIDS is the world’s leading infectious cause of death in adults.
If left untreated, the HIV-caused disease has a mortality rate of near 100%. In 2002, new HIV infections rose to 5 million, affecting 4.2 million adults (2 million of whom were women) and 800,000 adolescents and children under the age of 15. Finally, this year the epidemic claimed over 3 million lives. Of these, 2.5 million were adults (including 1.2 million women) and 610,000 were young people under 15. Thus, the estimated number of adults and children living with HIV/AIDS at the end of 2002 totalled 42 million.

In a report by UNAIDS on the possible evolution of AIDS over the next two decades, presented at the XIV International AIDS Conference in Barcelona, it was reckoned that, if the current rate continues, AIDS will kill 68 million people by the year 2020, and 67% will be women.
In other words, over 45 million women will die from HIV in the next 18 years, triggering nothing less than a generational cataclysm in regions such as Africa, where the majority of these deaths will occur.

The situation of the pandemia in industrialised Western countries belonging to what is known as the “capitalist world” bears little resemblance to that of poor countries, whether in the developing or emerging stages.
It is even less akin to others of uncertain destiny: those closer to the dynamic of extinction of their inhabitants in the reproductive age group as a result of HIV/AIDS-related disease or death. According to the report entitled Global Summary of the HIV/AIDS Epidemic, December 2002, the HIV/AIDS epidemic is only aggravating the deepening hunger crisis in Eastern Africa. This report states that the hunger suffered by this African region is a clear example of how the HIV/AIDS impact extends beyond the loss of life and healthcare costs associated with the disease. At present, over 14 million people risk starvation in Lesotho, Malawi, Mozambique, Swaziland, Zambia and Zimbabwe. These six societies face serious AIDS epidemics.

In Sub-Saharan Africa, the epidemic continues to grow. It is estimated that 3.5 million people were infected with HIV in 2002 and 2.4 million Africans died from the disease.
Furthermore, it has rapidly spread to new areas. The world’s fastest-growing HIV/AIDS epidemic is that affecting Eastern Europe and the republics of Central Asia. The year 2002 saw an estimated 250,000 new infections in this region, where the total number of people with HIV/AIDS reached 1.2 million. In certain countries, the epidemic is advancing at a truly alarming rate. In Uzbekistan, for example, almost as many new infections were reported in the first half of 2002 as in the entire previous decade. Likewise, certain Asian and Pacific countries, including China, Indonesia and Papua New Guinea, may also face huge growth in their epidemics. In Beijing in late 2002, it was admitted in fact that the number of seropositives had risen 16.7% in only six months. In Asia and the Pacific there are more than 7 million people infected by the virus. Moreover, a million new cases are detected each year due to the sex trade, unprotected sexual intercourse and drug addiction. Intravenous drug consumption is the most common means of HIV transmission in Western Europe, as well as in different countries in Asia, the Middle East and North Africa.

In Indonesia, for example, a sharp rise is being seen in this practice and, with it, the risk of a full-blown AIDS epidemic.
There, the infection rate among parenteral drug users is soaring, to such an extent that this means of transmission may be responsible for over 80% of the HIV infections that will occur in that country in 2003. In the Middle East and North Africa the disease is advancing slowly but surely, whereas in Eastern European and Central Asian countries AIDS statistics are showing a marked upsurge. Inhabitants of Latin America and the Caribbean are also among those most affected, with almost 2 million people with HIV/AIDS. Indeed, it is the leading cause of mortality in some countries. In Haiti and the Bahamas, HIV prevalence rates in adults surpass 6% and 3.5% respectively.

We see the other side of the coin in developed countries (Western Europe, North America, Australia and New Zealand), where prevention campaigns and treatments have managed to stabilise figures which are daunting nonetheless.
“HIV prevalence continues to rise in these countries owing to the efficacy of antiretroviral therapy, which succeeds in improving the survival and quality of life of patients.” Nonetheless, prevention programmes must be fostered, since unprotected heterosexual relations appear to have replaced the use of contaminated syringes as the principal means of transmission. Other alarming data refer to the concentration of cases in the marginalised populations of developed countries, and also to the impact on young people, since 50% of infections affect people of 15 to 25 years of age.

Evolution of the epidemic in Spain

The latest data supplied by the Spanish Ministry of Health and Consumption, National AIDS Plan reveal that 2,437 AIDS cases were diagnosed in 2002, with an increase of 23 notifications over 2001, when 2,414 cases were registered, in other words a rise of +/- 1%, which would mean a certain stabilisation in AIDS incidence and, with this, a change in the downward trend of previous years.
Thus, the decreasing rate of new AIDS cases, seen with the introduction of antiretroviral treatments in Spain, appears to have come to a halt. While from 1996 to 2001 there was a significant 60% drop in AIDS incidence, in 2002 the stability and slight upturn registered would suggest that the trend towards a steady decline in new cases is not going to be maintained over time. On the other hand, the so-called “HAART” era has meant increased life expectancy and quality of life for infected people receiving antiretroviral treatment. Around 150,000 men and women live in our country as HIV carriers.

As for the means of transmission, until now “the engine” of the epidemic in Spain has been the consumption of injectable drugs.
However, in recent years a rise, albeit moderate, has been registered in sexually transmitted infections. The data show us how, in 2002, the number of cases in which the infection was contracted through unprotected heterosexual relations rose to 27%, with women taking an especially relevant role, since they accounted for 44%. Furthermore, HIV exposure through sex between males accounts for 13% of all cases. We should also point out that the number of people with AIDS from different parts of the world registered in Spain has climbed to 10% in 2002. Another important factor that demands swift corrective action is related to the proportion of AIDS cases in people unaware that they are HIV-infected, and which in 2002 continued growing to the 38% mark. This percentage reached 65% among AIDS cases among those infected heterosexually.

XIV INTERNATIONAL AIDS CONFERENCE IN BARCELONA, 2002

The Fourteenth International AIDS Conference was held at the beginning of July in Barcelona, with the slogan “Knowledge and Commitment for Action”.
The conference was predominated by a significant and alarming report on the 10 million people in the entire world infected with AIDS who have no hope whatsoever of obtaining anti-HIV treatment. Activists and researchers agreed that stopping the AIDS epidemic depends, more than anything, on support by politicians and available monetary funds. Researchers presented proof that their work is improving our understanding of the HIV virus, helping us to set up better treatment strategies. Encouraging results were also seen in people who were already combining anti-HIV (HAART) medications, and in those waiting to undergo anti-HIV treatment. Further information appeared with respect to the utility of anti-HIV treatment under certain conditions for a planned period of time, which is known as structured treatment interruption, or STI (“therapy holidays”). Study after study proved that even tolerated medications may cause moderate to severe side effects over the long term. The extent of the liver damage caused by anti-HIV treatments drew enormous attention. One study concluded that people infected with HIV and Hepatitis C are more apt to die of liver problems caused by anti-HIV medications than of the hepatitis C infection itself.

Women and HIV was another vital issue addressed at this conference.
Today there is a growing number of women actively fighting HIV, both locally and internationally, and increasingly ready to demand that greater and more specific attention be given to the issues concerning them. This, however, was not reflected in the content of the official conference programme but rather in the satellite activities promoted by international associations of women who are not resigned to seeing these issues neglected.

What most stood out at the XIV International AIDS Conference with regard to Women and HIV was the confirmation of certain issues that had been pinpointed earlier.
As for the progression to AIDS, certain studies confirmed previous results in which it had been proven that, with equal viral load levels, there was no difference between men and women in terms of the evolution of the infection, either in treatment conditions or in the natural course of the infection. Treatment response was another important issue in which specific data were obtained on women. A study of treatment naïve patients revealed greater immunological response in women, and in the Atlantic Study no differences were produced between the sexes in terms of virological response to TARGA and toxicity. In contrast, differences were found with regard to analytical alterations, especially in hepatic toxicity (lower in women than in men). Finally, very few studies were presented on specific side effects in women. There is a need, then, for further gender-differentiated research which would lead to better situation analysis.

This conference was also marked by protest.
Many people living with HIV together with non-governmental organisation officials got it off to a noisy start by leading a democratic, peaceful demonstration against the Spanish government during the opening session. These protests were motivated by accumulated frustration and rage, aggravated by the lamentable policy of visas applied to conference participants. They also added that the expectations raised with respect to the commitments by industrialised countries in order to alleviate the dramatic situation of AIDS in developing countries had been thwarted, since no real new commitment had been made, and any modest ones made previously were not being honoured.

ACCESS TO TREATMENT

Specialists agree as to the need for investment in the treatment and the production of generic drugs in low-income countries.
To meet this objective, in May 2000 the United Nations reached an agreement with five pharmaceutical companies with the purpose of establishing prices that would adapt to the purchasing power of each country. This has meant that, now in 2002, 19 African, Caribbean and Latin American countries have access to cheaper drugs.

A new international alliance, the International HIV Treatment Access Coalition (ITAC), presented in Geneva and Dakar on 12 December 2002, proposed intensifying efforts aimed at providing access to antiretroviral medications to the ever-growing number of people affected by HIV/AIDS in the low- and middle-income countries that need them.
The coalition was created at a time of both crisis and opportunity. In the countries most affected, over a third of the adult population is now infected with HIV. Although the number of people receiving antiretroviral treatment has increased by almost two-thirds in Sub-Saharan Africa, in 2002 a mere 1% of the 4.1 million living with HIV/AIDS in the region and in need of treatment currently have access to antiretroviral medications. Nonetheless, there is a rising commitment to providing access to those medications through the public sector in Africa and elsewhere. Botswana, Costa Rica, Cuba, Nigeria, Senegal and Thailand have recently (2002) set ambitious treatment goals, and many countries have lowered import taxes and duty on HIV-related medications and articles.

NEW TREATMENTS

The most important new developments in anti-HIV treatments presented in Barcelona were therapies that are already or will soon be available.
These include advances in T-20 (at present known as enfuvirtide or Fuzeon) and atazanavir, two medications that will probably be approved in 2003. Another new medication likely to be approved is FTC (Coviracil), a close relative of 3TC (lamivudine, Epivir). Vital information was also released concerning tenofovir (Viread), a medication approved by the FDA in late 2001. Of equal importance were the new observations concerning certain older medications, especially the combination of ddI and d4T.

New and resistant medication: T-20 (enfuvirtide/Fuzeon)

This medication is listed under a new class of drugs known as fusion inhibitors.
T-20 stops HIV before it fuses with and infects another cell, thus preventing the production of more HIV-infected cells. This drug attacks HIV at a different infection level better than any other existing medication. Since it has a new form of action, T-20 is proving active against viral strains that have built up resistance to existing therapy, making it a very appealing drug for people with multiple virological failure and few treatment options.

Enfuvirtide’s principal limitation is that it cannot be administered in pill form and so must be injected twice daily.
Its main side effect is a reaction in the injection area, which affects practically all people taking it. According to the principal studies presented to the Food and Drug Administration (FDA), enfuvirtide was administered to people who had already developed a resistance to the three existing classes of medications and who needed a “rescue” therapy. In all probability, the high price forecasted for Fuzeon will limit its use to only those people for whom other alternatives have failed. Enfuvirtide is expected to be granted approval in March 2003.

ATAZANAVIR: a new protease inhibitor

Atazanavir is the newest addition to the class of protease inhibitors designed to be taken once daily.
The FDA is expected to approve it in early 2003, and at present (2002) it is available in a large expanded access programme. Most importantly, this is the first protease inhibitor that apparently does not cause potentially harmful effects to cholesterol and triglycerides levels, which probably reduces the risks of fat redistribution, cholesterol-related problems (including liver affections) which have been seen with other medications of this class. This plus the fact that it is administered once a day give atazanavir clear advantages over other protease inhibitors.

COVIRACIL (emtricitabine, FTC)

Emtricitabine is a new medication, thought to be similar to 3TC.
What clearly sets it apart from the latter is the fact that it is designed to be taken once a day and, furthermore, delays resistance development in comparison with 3TC.

Apart from these new drugs, in 2002 the FDA approved the rapid HIV detection kit (OraQuick), which provides 99.6% accurate results in only 20 minutes.
Unlike other tests for the detection of anti-HIV antibodies, this one can be stored at room temperature, requires no specialised equipment, and is considered for use outside the traditional laboratory or clinic. It is a known fact that many people taking the anti-HIV antibody detection test in public clinics often fail to collect the results of these analyses. The new kit seeks to eliminate this problem, and also makes users aware of their serological situation within minutes.

Summing up then, the year 2002 has confirmed the trend towards simplifying treatments and the single 3-pill daily dose now appears to be standard.
The potential of the new drug families, such as the aforementioned fusion inhibitors, also appears to have been established. In any event, prevention, education and information continue to be the basic pillars of the fight against AIDS.

2003

HIV/AIDS continues to be the world’s leading cause of death among adults in the 15 to 59 age group.
Since the first AIDS cases were identified in 1981, the disease has claimed over 20 million lives. Despite progress, current prevention and care efforts are insufficient. The global AIDS epidemic shows no signs of abating. In 2003 alone, 5 million people were infected with HIV, and 3 million died of AIDS worldwide. It is estimated that, by the end of 2003, between 34 and 46 million people will be living with HIV around the globe. It has also been calculated that approximately 14,000 new cases of HIV infection occurred daily in 2003.

If in 2002 importance was first given to the issue of women and HIV, in 2003 the epidemic’s female face has shown itself constantly.
Women are becoming increasingly exposed to the risk of contracting the infection. Until December 2003, they accounted for close to 50% of all people living with HIV throughout the world, and 57% of those in Sub-Saharan Africa. Indeed, women and girls bear the brunt of the epidemic. They are the ones most likely to care for sick family members, to lose their jobs and incomes, and to leave school as a consequence of the disease. They must also cope with the stigma and discrimination. There is an urgent need to address the different factors contributing to the vulnerability and risk of women, among them, cultural and gender-related inequality, as well as violence and ignorance. It should also be pointed out that young people between 15 and 24 years of age account for half of the world’s new HIV infections.

The epidemic continues to be non-homogeneous in terms of its magnitude or impact on regions. Certain countries are more affected than others, and, within the countries themselves, there are wide variations in the infection levels among different provinces, states or districts.

In Asia the epidemic is rapidly spreading.
This is most evident in China, Indonesia and Vietnam, where marked increases have been seen in HIV infections. In 2003 alone, 1.1 million new infections occurred in this region, a figure higher than any previous year, while an estimated 7.4 million people have been living with HIV. The fast-growing epidemic in Asia, where 60% of the world’s population live, has sweeping global implications.

In Asia, the HIV epidemic is still mainly concentrated among consumers of intravenous drugs, men who engage in sexual relations with men, sex workers, their clients and their immediate sex partners.
Next to South Africa, India has the highest number of HIV-infected people: an estimated 5.1 million in 2003. Nevertheless, the level of awareness of the virus and its transmission remains scant and incomplete. Another alarming fact is that many men who have sexual encounters with men may be infecting the women with whom they also maintain sexual relations.

In Asia, the HIV epidemic is still mainly concentrated among consumers of intravenous drugs, men who engage in sexual relations with men, sex workers, their clients and their immediate sex partners.

Next to South Africa, India has the highest number of HIV-infected people: an estimated 5.1 million in 2003. Nevertheless, the level of awareness of the virus and its transmission remains scant and incomplete. Another alarming fact is that many men who have sexual encounters with men may be infecting the women with whom they also maintain sexual relations.

In the case of Africa, it is estimated that some 25 million people were living with HIV in Sub-Saharan Africa in 2003.
While apparently HIV prevalence rates are becoming stabilised, this is largely due to an increase in AIDS deaths and a steady upsurge in new infections. Prevalence continues to rise in certain countries like Madagascar and Swaziland, while in others such as Uganda it is declining in the country overall.

Sub-Saharan Africa, which accounts for something more than 10% of the world’s population, is home to close to two thirds of all people with HIV. In 2003, some 3 million people were infected, while a further 2.2 million died of AIDS, which is to say 75% of the world’s 3 million AIDS deaths this same year.

It cannot be said that there is a typically African HIV epidemic.
Throughout the continent, vast differences have been seen in HIV levels and infection trends. In six countries, HIV prevalence is under 2%, whereas in another six it is over 20%. The seven Southern African countries present HIV prevalence levels over 17%, with Botswana and Swaziland showing rates over 35%. In West Africa, HIV prevalence is much lower. No country in that region has prevalence over 10% and, for the most part, the rate fluctuates between 1% and 5%. Adult prevalence in Central and East African countries is on a par with the western and southern parts of the continent, with values between 4% and 13%

African women run a greater risk than men of contracting HIV and become infected at an earlier age.
In 2003, Sub-Saharan Africa saw an average of 13 HIV-positive women per 10 HIV-positive men, in comparison with 2002’s 12 women per 10 men infected. The difference in infection levels between men and women is even more striking in young people between the ages of 15 and 24.

In North Africa and the Middle East, close to 480,000 people were living with HIV in 2003.
Systematic vigilance against the epidemic is not well developed there, a shortcoming that is glaringly obvious among high-risk groups such as intravenous drug consumers. And yet in most of the region HIV infection is concentrated in that precise group. Another source of concern is the likelihood of the virus silently spreading among men who engage in homosexual relations, since in many places such practices are widely condemned and illegal.

In Eastern Europe and Central Asia epidemic continues to spread, caused mainly by intravenous drug consumption.
In 2003, close to 1.3 million people were living with HIV, compared to approximately 160,000 in 1995. It is particularly significant that 80% of these people do not live to age 30. Estonia, Latvia and the Russian Federation are the countries most affected, but HIV is also spreading relentlessly in Belarus, Kazakhstan and Moldova. The most important driving force behind the epidemic in this region is intravenous drug consumption. Nonetheless, in certain countries sexual transmission is increasingly common, particularly between intravenous drug consumers and their partners.

The Russian Federation is still one of the countries most affected in the area.
Women make up a growing part of the new HIV subjects diagnosed: from one out of every four cases in 2001 to one out of every three in 2003.

In Latin America, around 1.6 million people were living with HIV in 2003.
The epidemic is concentrated among populations at high risk of HIV infection, which is to say intravenous drug consumers and men who engage in sexual relations with men.

In Latin America, around 1.6 million people were living with HIV in 2003. The epidemic is concentrated among populations at high risk of HIV infection, which is to say intravenous drug consumers and men who engage in sexual relations with men.

Three countries in the Caribbean area show national HIV prevalence rates of at least 3%: the Bahamas, Haiti, and Trinidad and Tobago.
Around 430,000 people are living with HIV in this region. In the Caribbean the epidemic is mainly heterosexual, and in many parts it is concentrated among sex workers. Haiti is the most affected country, with a national prevalence of around 5.6%, the highest outside of Africa.

In high-income countries, it is estimated that 1.6 million people were living with HIV in 2003.
Unlike the situation of other regions, the vast majority of people living with HIV in these countries and in need of antiretroviral therapy have access to it. Consequently, they stay in good health and survive longer than infected people from elsewhere.

Evolution of the epidemic in Spain

According to reports received by the National AIDS Registry, an estimated 2,190 AIDS cases were diagnosed in Spain in 2003, which, compared with the 2,311 estimated in 2002, is a 5.2% drop.
Although the number of cases continues to decrease, in recent years this decline has been more gradual, and one sees a trend towards stabilisation.

The incidence of mother-child AIDS transmission dips slightly, with an estimated 6 cases in 2003.
A slight rise was seen in the number of estimated cases in 2003 among men who contracted the infection through high-risk homosexual practices (8.2%), while those contracted through high-risk heterosexual practices fell slightly (3.6%) and those estimated among parenteral drug users (PDU) descended to 9.5%.

AIDS incidence is a good indicator for evaluating the activities aimed at controlling the disease: prevention, early diagnosis and treatment of HIV-infected people.
Early HIV diagnosis and treatment are the interventions having greatest impact on AIDS incidence. Following the introduction of high-efficacy antiretroviral treatments in 1996, the incidence of AIDS cases plummeted: 64% in 5 years. Yet, although the trend is a favourable one, the levels of AIDS incidence in Spain continue to be high in comparison with those of other European countries. To ensure that this decrease is sustained, there is a need to boost interventions aimed at promoting the HIV test and early diagnosis of the infection in those who have engaged in high-risk practices.

Among diagnosed cases, men continue to predominate (79.7%).
The average age of those diagnosed with AIDS has risen to 40 years. The proportion of paediatric cases (under 13 years of age) is 0.3%. Around half of those who developed AIDS in 2003 contracted the infection by sharing injection material for parenteral drug administration (49%), which affected 50.5% of the men involved and 43% of the women

The subjects that contracted the infection through unprotected heterosexual relations ascend to 27.9%, but this takes on special relevance in women, who account for 50.2%.
The third most common means of transmission was unprotected sexual relations between men: 15.1% of all cases and 18.9% of those affecting men.

The proportion of AIDS in people unaware of being HIV positive reached 38.1% in 2003.
This proportion is even higher (64.8%) in cases diagnosed in men who had engaged in high-risk homosexual relations, and in people infected as a result of unprotected heterosexual relations (58.4%).

Finally, AIDS subjects whose notifications indicate countries of origin other than Spain account for 12.9% of all notifications received in 2003.
The majority (80%) came from Africa and Latin America.

ACCESS TO TREATMENT

A large part of the history of activism concerning HIV/AIDS treatments arose out of the request for something that could alter the course of HIV infection.
In those early days of the epidemic, people tended to live a mere six months to a year after receiving the diagnosis. Faced with such a devastating panorama, they settled for the development of the first medications that would prolong life a further six months.

Approximately one decade later, with the arrival of protease inhibitors and three-drug “cocktails”, the treatments were adding years to life.
Yet soon rumours sparked over the difficulty of taking these therapies –one consisted of six pills daily, another could not be taken with meals, yet another had to be taken with food, and they could never be taken at the same time.

AIDS activists and people living with HIV then demanded simpler therapies and that was what we were given –many regimens involving a single daily dose (in progress), medications with fewer side effects, and a lower number of pills to be taken.

A decade ago there were three approved medications being used to fight HIV. Today there are more than 20, as well as a number of more sophisticated tools for controlling health.
Other medications are on the way, including a new class known as “entry inhibitors”. Furthermore, we shall soon have completely new strategies for fighting HIV, such as RNAi. A series of innovative evaluation tools are expected, such as health monitoring therapy.

Both AIDS activists and people living with HIV continue to call for the expansion of treatment programmes offering life-prolonging antiretroviral treatment.
Only 7% of those needing antiretroviral treatment in low- and middle-income countries have access to these medications, which is to say 400,000 people at the end of 2003. These programmes must be sustainable in order to prevent the development of strains that are pharmaco-resistant to the virus.

Despite the fact that the international AIDS expenditure has multiplied by 15, from USD 300 million in 1996 to something less than USD 5 billion in 2003, this is not even half of what developing countries will need in 2005.

NEW TREATMENTS

The Conference on Retroviruses and Opportunistic Infections (CROI) included the presentation of the large number of new chemical compounds being studied with the purpose of eventually being used as effective anti-HIV medications.

Among the totally new ones, since chemist shops still offer nothing comparable, we find those that block the binding of the virus to one of its new entrance doors to the cells:
these are inhibitors of one of the chemokine receptors, known as CCR5. Should the virus prove capable of going further and entering the cell, integrase inhibitors, such as V-165, are also being developed. These are molecules that prevent the genetic material of the virus from being integrated into the cell genome and from using it for its own purposes of replication.

Finally, mention should be made of the presentation of an immunoglobulin G, called TNX-355.
With its very precise biochemical design, this molecule blocks the lock (CD4) where the virus has to place the key (gp120) in order to open another entrance door to the cell. This process is already in the experimentation phase in patients, with very promising results.

As for improvements in treatment, during the congress a number of papers were presented on the controlled interruption of antiviral treatment.
None of the presentations proved its effectiveness. On the contrary, several claimed that it was an option to be avoided, especially in advanced AIDS patients. It should be added that, even in cases of treatment interruption in patients who began therapy immediately after infection and who appeared to be the group that could benefit from this therapeutic strategy, the hopes of obtaining a long-term control of viral replication without drugs are fading.
Nevertheless, the option remains of controlled treatment interruptions with the aim of reducing pharmacological toxicities while maintaining the patient’s immune state, yet without claiming viral control.

As announced at the Barcelona AIDS Conference in 2002, the new medications approved by the FDA in 2003 are Fuzeon (T-20), Emtriva (FTC) and Reyataz (atazanavir).

Studies into the development of immunity to the virus (vaccine) continue, making it clear that the design of new antibodies for use in prophylactic or therapeutic vaccines should be based on structures that are much more adapted to HIV’s biological targets, since by the time the human body succeeds in producing antibodies which can effectively fight the virus, the latter has already mutated, meaning that the immune system has to once again begin to produce new antibodies, and so on and so forth.

For all of the foregoing reasons, it is clear that an integral strategy combining prevention, treatment, care and support for those affected by HIV/AIDS could save millions of lives.

2004

SITUATION OF HIV/AIDS DURING 2004

In 2004, the total number of people living with human immunodeficiency virus (HIV) reached its highest level: some 35.9 – 44.3 million people are estimated to be living with the virus.
The number of people living with HIV has risen in all regions when compared with the two preceding years, although the largest increases have occurred in eastern and central Asia and eastern Europe.
The number of persons living with HIV in eastern Asia rose by nearly 50% between 2002 and 2004, mainly as a result of the rapid growth of the epidemic affecting China.
By 2004, eastern Europe and central Asia had 40% more people living with HIV than in 2002. Much of this increase is attributed to the resurgent epidemic in Ukraine and the rising numbers of people with HIV in the Russian Federation.
Sub-Saharan Africa remains by far the worst-affected region, with 25.4 million people living with HIV by the end of 2004, as against an estimated 24.4 million in 2002.
Just under two-thirds (64%) of all people living with HIV are from sub-Saharan Africa, as are over three-quarters (76%) of all women living with HIV.
This prevalence is tantamount to saying that approximately the same numbers of people continue to become infected by HIV and to die as a result of AIDS. Furthermore, the epidemics in Africa are diverse in terms of their extent and the rate at which they develop.
The prevalence of HIV in the Caribbean is the second highest in the world. Five countries have a rate exceeding 2%, while AIDS has become the principal cause of mortality among adults aged 15-44 years.
As regards prevention, programmes are required that help to prevent the propagation of HIV among the most vulnerable population groups. In many countries, however, insufficient funds and a lack of political will and leadership remain obstacles in the way of the struggle against AIDS, particularly in places where HIV has taken hold among marginalised and stigmatised population groups, such as women who have sexual relations in exchange for money, intravenous drug users and men who have sexual relations with other men.

Women increasingly affected
The AIDS epidemic is affecting increasing numbers of women and girls. Worldwide, a little under half the people living with HIV are women. Women are affected more severely in those places in which heterosexual relations constitute the predominant way that HIV is transmitted, as in the cases of sub-Saharan Africa and the Caribbean.
Women and girls make up nearly 57% of all the people infected by HIV in sub-Saharan Africa, where a devastating 76% of the young people (aged 15 to 24 years) who live with HIV are girls.
These trends highlight serious differences in the response to AIDS, showing that services that can protect women against HIV must be extended.
A recent survey by the United Nations Children’s Fund (UNICEF) showed that 50% of the young women from countries with a high prevalence were ignorant of the basic issues about AIDS. But women’s and girls’ vulnerability to infection by HIV is not due simply to ignorance: it is due also to their widespread lack of emancipation. Most of the women who are infected worldwide by HIV are so infected due to the high-risk behaviour of their partners, over whom they have little or no control.
The pressing situation of women and girls in the face of AIDS highlights the need to put into practice effective strategies that tackle the interrelation between inequality (particularly sex-based inequality) and HIV.

Due to all this, at the beginning of 2004 UNAIDS created the Global Coalition on Women and AIDS to draw attention to the effects of HIV and AIDS on women and girls and to stimulate effective action to allow their impact to be reduced. The Global Coalition on Women and AIDS is not a new organisation, but rather a movement of persons, networks and organisations supported by activists, leaders, government representatives, community workers and well-known personalities. Its work focuses on seven areas:
• Preventing HIV infection among adolescent girls.
• Reducing violence against women.
• Protecting the rights of women and girls to property and inheritance.
• Ensuring women’s and girls’ access under equal conditions to care and treatment.
• Supporting better community-based care, with special emphasis on women and girls.
• Promoting access to the new prevention options, including female condoms and microbicides.
• Supporting ongoing work directed at universal education for girls.

Evolution of the epidemic in Spain

According to notifications received, it is estimated that 2,034 cases of AIDS were diagnosed in Spain in 2004. Compared with the total of 2,279 cases estimated in 2003, and after correcting for delays in notification, this amounts to a 10.7% fall. The reduction mainly affects men, who show a 13.6% reduction in relation to 2003.

Between 2003 and 2004 the cases diagnosed in parenterally administered drug users fell by 13.6%, this being the most numerous group and the one that has shown the sharpest drops in recent years.
Cases of infection due to unprotected heterosexual relations fell by 11%, while those due to sexual relations between men were down 6.8%.
The incidence of mother-child transmission was also slightly reduced, with an estimated 3 cases in 2004.

Among the group of persons infected by sexual transmission, more than 60% of the new cases diagnosed were unaware of their HIV seropositive condition, which means that over half of the people in a state of advanced illness had been living with the virus for a decade without having undergone an AIDS test and thus without having undertaken treatment of any kind.

The incidence of AIDS is a good indicator for assessing the frequency and evolution of advanced stages of HIV infection in the population. It is also a key factor in assessing the effectiveness of treatments and in diagnosing the infection early — the two measures that most successfully counter the progression of AIDS. Cases of AIDS provide no information about the frequency of new HIV infections in the population, however, nor about its recent evolution, so that new infections can be rising while AIDS cases are following a downward trend.
Given the increased use of the new antiretroviral treatments in 1996, the incidence of AIDS has decreased by 69.5% in Spain, with one major decrease over the 1997-1999 period and another more moderate one from 2000. Spain nevertheless remains one of the Western European countries with the highest incidences of AIDS. In order to maintain the fall in cases of AIDS it is necessary to boost efforts directed at promoting HIV testing and early diagnosis of the infection in people who have engaged in high-risk activities.

Persons with AIDS whose notification records show a country of origin other than Spain accounted for 13.6% of the notifications received in 2004, with most coming from developing countries in Africa and Latin America.
The proportion of cases of AIDS in persons who did not know that they were HIV-infected reached 37.5% in 2004. This proportion is higher still among people who became infected by unprotected sexual relations (60.8% among heterosexuals and 57.5% in homosexual relations between men).

XV INTERNATIONAL AIDS CONFERENCE IN BANGKOK, 2004

The XV International AIDS Conference held in Bangkok was attended by 17,000 participants from 160 countries, making it the largest to date in that continent.
The conference was run under the slogan “Access for All”, with the aim of emphasising access to treatment and at the same time access to science, prevention and resources for all.
The conference agenda included a wide range of activities, divided into several programmes: leadership programme, community programme, scientific programme and activities implementation programme.

During the conference, the Thai Minister of Public Health stressed that Asia contributes each year one quarter of the new infections in the world and that, after the sub-Saharan region, Asia is the second most seriously affected region in the world.

As part of its commitment, the Thai government has for some years now been implementing robust prevention and care policies and measures. In terms of care, the government has been producing generic antiretroviral medicines directly since 1992, when it began with AZT in order to increase cover and reduce costs; it now produces several antiretrovirals and the costs have gone down dramatically.
By producing generic drugs the government aims to respond to the needs of a country in which at present only 5% of those with HIV receive drugs for it, thereby facilitating follow-up treatment, increasing cover and reducing costs.
The conference was nevertheless interspersed with constant protests by community activists requesting access to generic treatments, while hundreds of marchers paraded with banners bearing messages such as “While you are talking we are dying”, “Access to treatment now!”, and others.

The Bangkok objectives thus accorded priority to having the leaders’ agendas and countries’ measures include an urgent increase of cover in care and access to treatments. In this respect, since the Barcelona Conference in 2002, the Global Fund to Fight AIDS, Tuberculosis and Malaria has approved a number of projects directed at increasing treatment cover, and oversaw the WHO and UNAIDS initiative known as 3 x 5 (three million people receiving treatment by 2005).
In the meantime, however, over this 2002-2004 period six million people have died and a further ten million have been infected.
It was made clear in Thailand that we had seen 20 years of promises, while the epidemic continued to advance throughout the world, though particularly affecting poor and vulnerable populations. Only one in five people in the world has access to HIV protection, and by the end of 2003 only 7% of the 6 million people requiring treatment in the developing countries were in fact receiving it.

In the course of the Conference, the presentations on the subject of prevention mainly focussed on the need to work with the most vulnerable population groups, and especially with the young people and women among whom the epidemic continues to grow alarmingly.
Women are living at risk. Bangkok once again placed the emphasis on actions seeking an improvement of their social and economic setting, a reduction of the violence of which they are victims, increased education, protection for their rights and ensuring equality in care, treatment and prevention services.

The XV International AIDS Conference finally came to a close with presentation of some of the conclusions and commitments taken on in the course of the conference. In relation to treatments there was discussion of the options for new drugs that are currently in the experimental phase and have other forms and loci of action. Emphasis was also placed on research to gain a fuller knowledge of HIV and its variants (strains, recombinations, etc.). Research in the sphere of vaccines and microbicides was presented as a pathway towards hope.

Criticism was directed at the three-pronged strategy of abstinence, faithfulness and use of the condom, for it was being reduced to the first two elements while the third (the condom) was being neglected.

It was concluded that it was not right to speak of prevention versus treatment and care (i.e. making them mutually exclusive), but rather of the importance of prevention plus treatment plus care as an integral strategy, for each factor is important.

There was further discussion about young men and women, the poor and married women as the most vulnerable population groups, and it was noted that more young people of both sexes had taken part in this conference than in the Barcelona conference. A request was issued to make the next conference a faithful reflection of the “access for all” slogan by reducing the registration costs that placed it out of reach of precisely the most vulnerable groups of the population.

NEW TREATMENTS

Over the last years of the 1990s, protease inhibitors and non-nucleoside reverse transcriptase inhibitors were brought into the treatment of infection by HIV.
These drugs opened the door to what is today known as highly active antiretroviral therapy (HAART). The increasingly widespread use of HAART resulted in a change that had a great impact on the HIV epidemic, with a very marked reduction of opportunistic infections and of the mortality associated with AIDS.
These treatments gave rise to initial euphoria, and even claims that the infection could be eradicated following three years’ use of HAART. That initial optimism nevertheless gave way to the current situation, in which we now know that it is practically impossible to eradicate the disease, at least with the present-day drugs, and in which in the fulfilment of HAART regimens the adverse side-effects that arise and the emergence of resistance are of crucial importance in the treatment of this disease. These factors mean that research currently continues into new ways of treating HIV infection, seeking out new targets and drugs that are easier to take, as well as according consideration to new therapeutic strategies.

Immunotherapy consists in a new therapeutic strategy posited as an alternative and/or complement to HAART. Basically, the idea of immunotherapy lies in boosting the immune system so that it defends itself better against the damage caused by the virus.
Although a great many approaches have been taken to the immunological treatment of infection by HIV, they can at present be summed up under three broad headings:

Treatment with cytokines: the cytokines are proteins produced by the immune system’s own cells and have the mission of sending information to the other cells in the immune system so that the latter can carry out certain functions.
The cytokines most widely investigated in treatment of infection by HIV are interferon, GM-CSF and interleukin-2.
Interferon is a substance produced by the leukocytes, especially when they are infected by viruses. It acts by increasing antigen presentation from some cells to others to enhance the immune response, inducing the production of memory lymphocytes, boosting lymphocyte activation and reducing viral replication.

Therapeutic immunisations: therapeutic immunisations seek to induce specific immune responses to HIV in patients already infected by the virus. The hypothesis is that the immune system itself should end up controlling the infection, so that the patient needs less retroviral treatment. Three different types of therapeutic immunisations have been tested against HIV infection: recombinant proteins, inactivated virions and recombinant viruses.

Structured interruptions of the treatment: one of the problems with HAART is that when it completely inhibits viral replication it leads to the disappearance of the circulating virus and cessation of immunological stimulus. Any scant specific responses to HIV that might have existed prior to the treatment thus end up disappearing completely. In order to get round this problem it was felt that if the treatment was suspended for very short periods and the HIV was allowed to reproduce for a short time then further specific immune system responses could again be generated against the virus. And if these interruptions were repeated over the course of several cycles, then an immune response might be generated that could even control HIV replication if the treatment were suspended definitively.
Several studies have shown that such interruptions do indeed generate specific immunological responses to HIV, and in some cases achieve less viral replication with each interruption, so that the viral load reaches increasingly low levels. When patients definitively suspend the treatment at the end of the study, however, most patients have to recommence their treatment quickly due to a fall in CD4 lymphocytes or major increases of viral load, with loss of the immune responses generated. This type of therapeutic strategy is therefore being abandoned, though not entirely ruled out.
Some preliminary data suggest that if such interruptions were combined with some of the types of therapeutic immunisation noted earlier, then the need to reintroduce the treatment could be significantly delayed.