Issue Contents  Rights and risk reduction Vaccine update HIV vaccines on trial? Challenging HIV Slow steps forward? No quick fixes for prevention Strategies for development Ethics are essential Preventing HIV in prisons Reaching people behind bars Educate for protection Concerns for care Rope of hope Clinical update Respiratory diseases and HIV Bacterial pneumonias Pneumocystis carinii pneumonia (PCP) Clinical tuberculosis Kaposi sarcoma (KS) Fungal infections Management approaches Prevention measures Possible steps in second line management Letters New resources

Rights and risk reduction

Efforts to ensure people's rights to health care, education and freedom from discrimination are widely acknowledged to be essential to HIV control. The people who are at highest risk of HIV through unsafe sex or drug use are often those with the least power to change the situations that involve risk or whose needs are badly neglected. Prisoners are one such group. Their human rights are abused in most countries, and millions are held in overcrowded and dirty conditions. Without knowledge of the risks or access to protection, both male and female prisoners are extremely vulnerable to HIV infection, through forced or consenting high risk activities. As the Brazilian educator featured on page 5 points out, even just a brief period in prison can become a death sentence if a person is infected with HIV. And it is not only inmates who are at risk - after prisoners are released into the wider community, HIV may be spread to others. In view of these issues, WHO has recently announced its strong support for strategies such as condom distribution in prison, because prisoners have the same rights as other citizens to health care, including preventive measures.

No high hopes 
A safe and effective vaccine to prevent HIV infection could be ready for testing with large groups of people within the next five years. Experts are already planning the design of vaccine trials in countries including Rwanda, Thailand, Brazil and Uganda. Making sure that the trials do not abuse people's human rights is as important as overcoming the problems of vaccine development. On pages 2 and 3, AIDS Action explores some of the ethical and technical challenges.

But it is unwise to hope that HIV will be controlled through vaccination. A vaccine would playa role in prevention - immunising against infection with a simple injection or a pill is much easier and quicker than changing sexual behaviours. However, even if an effective and inexpensive vaccine were developed, the hard work of education and counselling about HIV and STDs, and treating curable infections, must always be at the heart of prevention efforts. 

Vaccinating every person would be an enormous task, especially in light of the fact that the most vulnerable people are often the poorest and most difficult to reach. People must consent to be vaccinated, and if they have had no education about HIV, they would be unlikely to come forward for immunisation. HIV prevention is forcing us to confront many other human rights issues. Not least of these is the need for women to have more control over their lives (including sex), in order to be able to protect themselves and their children from HIV infection. Increasing people's self-esteem and independence goes hand-in-hand with HIV prevention. It would be an immeasurable loss if vaccination programmes were to replace these efforts, because they are achieving much in terms of human rights as well as HIV control.

In this Issue   Update to HIV vaccine progress Page 2 Preventing HIV spread in prison Page 4 HIV-related respiratory infections Page 6

HIV vaccines on trial?

Research into HIV vaccines continues, but there are still many obstacles to overcome. AIDS Action explains some of this issues.

Since the mid 1980s scientists have been trying to develop vaccines against HIV that can carry out at least one of the functions below.

	‘Preventive’ or ‘prophylactic’ vaccines would protect HIV-negative people from infection and would also reduce rates of transmission, because fewer people would become infected. This type of vaccine is thought to be the least difficult to develop.
	‘Therapeutic’ or ’treatment’ vaccines would slow down or reverse the effect of HIV after infection. However, scientists have not yet succeeded in developing effective therapeutic vaccines for any viral infection, and many believe that there is little hope of  a vaccine for people who are already infected with HIV.
	‘Perinatal’ vaccines would be for HIV-positive women who are, or likely to become, pregnant. Ideally a perinatal vaccine would have a therapeutic effect for the woman and prevent infection of the fetus or infant.

Challenging HIV
 

No quick fixes for prevention Even with a highly efficient preventive vaccine, and the best vaccination policy, the number of people with AIDS will continue to grow, because millions of people will have already been infected with HIV. HIV prevalence will also continue to increase. Vaccinating all adults will be impossible in the short term, if ever, given limited resources. Targeting people at high risk is a possible strategy, but could increase stigmatisation and involve mistaken assumptions about who is at risk and why. However, in communities where many adults are already infected, it may be most important to immunize young people before they are sexually active. Without universal coverage, it will still be essential to educate people about practising safer sex. A vaccine could give people a false sense of security and reduce efforts to prevent other STDs and promote sexual health.

Slow steps forward?
All possible or candidate vaccines must go through a series of rigorous tests to make sure they are safe and effective for humans. After initial laboratory research, there are three main stages of testing.

Preclinical trials: a large number of experimental HIV vaccines are currently being tested in animals to assess: safety; ability to stimulate immune responses (immunogenicity); and ability to protect against HIV infection or disease progression (protective efficacy). Some have shown limited success, and have entered phase I/II trials.

Phase I/II clinical trials are designed to find out whether vaccines are safe and if they can stimulate an immune response in humans, but not if they protect against infection. They involve a small number of volunteers, without a control group. A number of possible vaccines have been tested with both HIV-negative and HIV-positive volunteers, mostly in the USA. Both groups showed a limited immune response and very minor side effects. But there is no information on clinical benefits for the HIV-positive volunteers or the long-term safety of the vaccines. Trials with HIV-positive women to prevent pregnancy-related transmission have recently started.

Phase III clinical trials are designed to test for a vaccine's ability to protect against HIV infection or slow down disease progression. No phase III trials for either preventive or therapeutic HIV vaccines have taken place yet. The trials will be: 
 

	large scale, involving thousands of people
	controlled (after random division of selected participants into two groups, one group will be given a placebo or non-vaccine substitute and the other will be given the vaccine, but otherwise both groups will be treated in the same way)
	double blinded (neither participants, health workers nor researchers will know who received the vaccine or the placebo).

Strategies for development
WHO is working with four countries - Brazil, Thailand, Rwanda and Uganda - to plan HIV vaccine research and trials. Their national plans include:
 

	studying different virus strains in the country
	carrying out clinical trials, especially
	further phase I/II trials of selected candidate vaccines
	researching patterns of infection and incidence
	researching the ways in which vaccine trials could affect sexual behaviour and attitudes towards sex
	ensuring that the health care system can provide advice, counselling and treatment.

These activities are supervised by the health ministry and are guided by a national committee which may include NGOs. WHO provides technical and ethical advice to these committees and co-ordinates liaison with other international institutions, including the pharmaceutical companies which are developing the vaccines. WHO aims to have an advisory role with companies and research institutions that are planning other trials, in China for example.

Thanks to Jorge A Beloqui, Grupo pela VIDDA-SP, CP 08350, 01 065-970 Sao Paulo, Brazil, Stephen K Lwanga, Uganda AIDS Commission (presentation at 8th international AIDS conference) and Dr Jose Esparza, Vaccine Development Unit, GPA/WHO, Geneva, Switzerland.

Ethics are essential

Thousands of people could be taking part in preventive HIV vaccine trials within the next five years. WHO and others are trying to draw up ethical guidelines to ensure that these trials respect people's rights to education, information and health care. But there are many difficulties.

Questions about participation A vaccine's success in protecting against HIV will be tested by seeing how many individuals become newly infected in the vaccinated group compared with the placebo group, over a period of time. Trials can involve fewer people, last for a shorter time and cost less if they take place where there is already a high number of new infections each year. These smaller trials could take place anywhere if they involve people in communities with high HIV incidence. However, worldwide the highest rates of HIV are often among people who are already vulnerable to discrimination, such as sex workers or injecting drug users. In Brazil, where trials are likely to involve men who have sex with men, NGOs and activists are worried that research and participation could expose people to increased prejudice and stigma.

Access to the vaccine WHO-sponsored trials are being planned with governments in some developing countries where HIV incidence is high, such as Uganda. These governments are seeking guarantees that a successful vaccine will be affordable. Some vaccines, against hepatitis B for example, are too expensive for use in the developing countries where they were tested. But even if an inexpensive vaccine is made available, lack of resources means that the need for this must be considered in relation to other budget priorities.

Education for all Involvement in the trial will not mean that participants are safe from infection, and they and their partners will need education about safer behaviour. As a result some, but not all, participants will have safer sex sometimes, but probably not always. Some behaviour will remain unsafe. However, safer behaviour means fewer newly infected people, which means involving more participants to ensure statistically significant results.

Need for informed consent Individuals should be able to freely choose to participate in a trial. Decisions should be based on full knowledge of the implications of taking part, including the fact that being vaccinated may cause an HIV-positive test result, though this will not necessarily mean that someone is HIV-infected. However, if people are not used to Western models of medicine they may find it difficult to understand the trial design, and the risks involved. In certain cultures individual decision making is unfamiliar, and families or community leaders may have to be involved. Pressure on people to participate and use of incentives must be avoided. However, access to health care may encourage many to volunteer in poorer countries.

Providing care Care and education costs will be large. Each possible participant must consent to have an HIV antibody test (with pre-and post-test counselling about the implications). People who test antibody positive will not be able to participate in trials for the preventive vaccine, but they (and their families) will need follow-up care and counselling. Participants will need access to health care during the trial and afterwards, if for example they experience any medical problems caused by the vaccine. 

Prisoners are at risk from HIV - and efforts to prevent transmission in jails protect people in the wider community too.
Evidence for high HIV infection rates among prisoners is growing. Worldwide, most prisoners are from poorer sections of society with a higher prevalence of HIV/STDs. This means that the proportion of men and women in prison who are HIV-positive may be greater than in the rest of society. Sex workers and drug users may be at particular risk of HIV, and are often imprisoned in places where prostitution and drug use are illegal. Up to 30 per cent of prison inmates in cities in the USA where illegal drug use is common are serving sentences linked with drug use or related crimes. People also risk being infected with HIV during their prison sentence. Both female and male prisoners are vulnerable to sexual assault by prison staff and other prisoners. Surveys show that sex between prisoners happens, in spite of severe penalties. For example, between 2 to 30 per cent of inmates in prisons in the UK, USA, Australia and Brazil reported sex with other inmates, which often involved unprotected anal intercourse for men. In a survey of five prisons in Zambia, over 12 per cent of male prisoners reported sexual experiences - both forced and consensual - with other men during their time in prison. Some prisons allow conjugal visits, when prisoners can have sex with a visiting partner which, if unprotected, could spread HIV. Drugs are often illegally smuggled into prisons, and obtaining clean injecting equipment is very difficult. Sharing needles and syringes is a common high risk activity. Body tattooing, scarring or piercing with shared instruments can also involve risk. Preventing HIV transmission in prisons not only protects prisoners, but others in the wider community too. Most inmates are in prison for brief periods only, and return to their home communities when they are released. If they are infected they could pass the virus to others through unsafe drug use or unprotected sex.

Collective response: in 1991 inmates of Santo Boma prison, in Paramaribo (in Surinam, Latin America) were invited by prison authorities to form the 'Boma Education Collective' after a survey showed that unprotected anal sex was common. After training in peer education, they developed and tested posters and leaflets and organised an HIV/STD awareness week. Prison warders also received training and a confidential counselling service was set up.

Christel Antonius, NAP Surinam, c/o 4205 NW 36th Ave, Miami, FL 33142-4217, USA.


Educate for protection
Increasingly prisons are introducing measures to reduce the spread of HIV. Both staff and inmates should be involved in developing a programme and putting it into action. Education about HIV/STDs, safer sex and injecting drug use is an essential part of programmes. Staff need training to help them deal with their own and inmates' fears of infection and prejudices about AIDS, and how to protect themselves from, for example, contamination with blood.

In some prisons, AIDS committees with staff and inmate representatives co-ordinate training, materials production and special events, such as drama. Peer education is useful since most practices involving risk are illegal, and prisoners themselves are more likely to be trusted by other inmates.

Distributing condoms in prisons is another important strategy for reducing prisoners' risk. Some prison authorities accept that they cannot prevent all sexual activity. They feel that providing condoms strengthens education efforts, enables prisoners to take care of themselves, and is likely to reduce the spread of HIV/STDs. A recent WHO-sponsored report showed that condoms are now available in prisons in over half of the countries surveyed, including Brazil, Canada, Costa Rica and many European countries(1). Some prison services, such as in Botswana and Cuba, distribute condoms only before parole periods and on release. Prisons in, for example, Australia, Spain, Mauritius, Tanzania and Costa Rica, provide disinfectant or bleach, and encourage inmates to sterilise needles and syringes and cutting instruments. By 1993, needles and syringes themselves had not been made legally available in any prison, although one women's prison in Switzerland had begun a small needle exchange scheme.

Management approaches

A rational approach to diagnosis and management of respiratory infections is based on knowing which ones are common in a particular region, and on available diagnostic facilities. A diagram (algorithm) showing the different steps to take according to the results of diagnosis and treatment may help health workers. The example shown below was developed for a hospital in Zimbabwe.

First line management 
If a history and a physical examination indicate bacterial pneumonia and the patient is not in respiratory distress, the infection should be treated with a penicillin. The signs of respiratory distress are a respiratory rate of over 24 per minute, intercostal muscle indrawing, use of neck muscles during breathing and central cyanosis (blue tongue and lips).

Second line management If the patient is in respiratory distress; or if there is no response after three days of treatment with a penicillin; or if the patient's condition worsens, these steps should be taken. 

If facilities are available, a sputum smear for acid fast bacilli for TB, a gram stain (for bacteria) and a chest X-ray should be carried out, and the patient treated accordingly (see diagram).

If facilities are not available, and it is impossible to refer the patient, a second antibiotic such as normal dose cotrimoxazole will cover many resistant pneumonias, and improvements should be seen within three days. Alternatively, extremely breathless patients should be given high dose cotrimoxazole for possible PCP as well as resistant pneumonias. This should be prescribed with caution, as it can cause side effects such as severe rashes (Stevens-Johnson syndrome). If the patient does not improve after 7-10 days of high dose cotrimoxazole treatment then smear-negative TB may be the diagnosis.

Dr Adam Malin, Nuffield Dept of Clinical Medicine, Oxford University, UK (formerly at the Dept of Clinical Pharmacology, University of Zimbabwe).

References are available from AHRTAG. WHO's guidelines for the clinical management of HIV infection in adults cover respiratory infections, and are available from DST/GPA, WHO, CH-1211 Geneva 27, Switzerland.


Prevention measures
 

	Smoking can hasten the onset of AIDS and increase the risk of bacterial pneumonias in HIV-positive people.
	TB screening should be carried out if a person with HIV has had contact with someone with TB, and TB treated if necessary.
	Prevention of some respiratory infections with drugs is possible.   Penicillin prophylaxis may prevent pneumococcal infections, and be valuable for people who have had severe recurrent attacks PCP can be prevented with a daily 960mg dose of cotrimoxazole, and can be considered if the infection is common.  Prophylaxis with isoniazid may prevent clinical TB from developing, and the effectiveness of this is still being studied.
	The existing pneumococcal vaccine is of limited value for people with HIV because it produces a very low immune response.

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