As a result of UNGASS and the drug-access activism that had preceded it at the Durban World AIDS Conference in 2000, the World Health Organisation (WHO) announced in 2003 a campaign to get three million people treated with antiretroviral drugs by the end of 2005 (half the number thought to be in life-or-death need).

The WHO announced in June 2005 that nearly one million people were now on antiretrovirals (ARVs). This was 600,000 fewer than their target for that month and they admitted that the three million goal would not be met.

However ‘3 by 5’ does seem to have served as a catalyst for accelerated drug access during the two years of its existence. In sub-Saharan Africa, half a million people -11% of those in need - are now thought to be on ARVs (up from 310,000 six months earlier). In south and south-east Asia the number on ARVs increased threefold from 55,000 to 155,000 in the year from June 2004 to June 2005. In Latin America 63% of people in need of ARVs are now taking them. And in Eastern Europe the number on ARVs has nearly doubled, from 11,000 to 20,000.

‘3 by 5’ has been the first set of HIV treatment goals specifically linked to a programme of action and it has involved countries and international agencies finally tackling the huge barriers to the treatment of disease previously thought so expensive, complex and life-long that scaling-up treatment was impossible. In order to do this the WHO included the following basic recommendations if scale-up or ARV treatment was to become a reality:

• Political commitment: Of 49 WHO/UNAIDS "focus countries", 40 have established national targets for treatment access, and 34 are developing or have completed implementation plans. These plans are a first step toward rapidly scaling up ART access. The WHO/UNAIDS report calls for countries that do not have concrete plans to put them in place quickly.
• Standardized approaches and increased capacity: The countries making the most significant progress in providing quality ART to the greatest number of people are those that have adopted standardized drug regimens and clinical monitoring procedures. These countries are also addressing bottlenecks in procurement and supply chain management and in human resources capacity – by training non-physician health workers to safely and effectively administer ART. More countries should follow these leads.
• Technical support: WHO and other UN agencies are in the process of increasing technical assistance to countries in scaling up their ART programmes and strengthening their health sectors overall. A key WHO initiative employs new mapping software to help countries pinpoint the greatest unmet needs for a range of health services, in order to best target available resources. Overall, there is a need for technical assistance agencies to better coordinate with each other and with donors. The new UNAIDS Global Task Team is one forum for promoting this kind of improved cooperation.
• Sustainable financing: Donors have committed a total of US$27 billion over the next three years for HIV/AIDS treatment, care, and prevention efforts. However, not all of these commitments have been delivered, and the total amount pledged leaves a projected shortfall of at least US$18 billion for the period 2005-2007. Donors should accelerate funding disbursements to countries, increase their commitments, and pledge long-term, predictable funding. Developing countries should continue to invest their own resources. The new G-8 debt relief proposal provides an opportunity for several countries to reallocate significant resources to HIV/AIDS.
• Linking treatment and prevention: Evidence is emerging that ART availability leads to an upsurge in demand for HIV testing and counselling and other prevention services. In one district in Uganda, introduction of ART led to a 27-fold increase in demand for HIV testing and counselling. The WHO/UNAIDS report recommends steps for countries to integrate HIV treatment with testing and prevention, including using the same health clinics to offer both treatment and testing, and training health workers who administer ART to also offer prevention.

Of these, the biggest barrier to scale-up is technical and human capacity. Universal ARV treatment will involve an extraordinary expansion and in some cases re-creation of healthcare systems reduced to skeleton services by years of neglect, underfinancing and the ‘brain drain’ or qualified medical personnel to developed countries.

ARV scale-up can be a challenge even to middle-income countries. In South Africa the 3 by 5 campaign estimates that 10-14% of the population in need of ARVs currently gets them, with wide disparities between different provinces. The South African Health Department plans to get ARVs to one million people by 2009 – pretty much the total of people who need them now, in September 2005. But the research organisation Health Systems Trust calculated that this would cost the country US$1 billion – 20 times what was being currently spent. An additional 3,200 doctors, 2,400 nurses, 765 social workers and 765 dietitians would be required to distribute and monitor ARV treatment.

Faced with this, one of the most exciting developments in some countries has been the recruitment of people with HIV themselves as peer treatment support workers.

Other barriers to access include:

• HIV stigma. Although studies have found that HIV stigma generally reduces when people realise that treatment works and is available, there have been reports from countries like Ghana and Nigeria that reluctance to come forward for voluntary counselling and testing was restricting the number of people treated. In Botswana President Festus Mogae announced in 2004 a controversial policy of routine opt-out HIV testing for people having medical checkups to increase the proportion of people who, in a country with 35% prevalence, know their HIV status from 8% to 100%.
• Resistance. In 2004 a study (Kamya) found that one-third of a group of 137 patients at Mulago Hospital in Kampala, Uganda had failed antiretroviral therapy after an average follow-up period of 38 weeks, with 22 per cent acquiring resistance to NNRTIs.
• Second-line treatment. The proportion of people who respond virologically to first-line regimes is 50% to 80% - similar to the proportion in developed countries, confounding predictions of poor adherence, but dependent on the potency and purity of drug regimens. Second-line treatments generally involve the more expensive protease inhibitors. During the summer of 2005 Brazil, which has pioneered universal HIV treatment in non-rich countries, was involved in a protracted negotiation with major Pharmaceutical company Abbott to reduce the price of its PI Kaletra (lopinavir/r). In September 2005 a group of Ugandan doctors criticised the country’s national HIV programme for only supplying drugs to drug-naïve people, saying that people who had been able to pay for first-line regimens were being discriminated against if they found they could not afford second-line ones (Colebunders).
• Drug prices. Although huge reductions in the prices of drugs have been negotiated, many countries still require patients to make co-payments on their ARVs. In the Uganda study cited above the main reason for treatment failure and the acquisition of resistance was poor adherence. In a cross-sectional questionnaire, eleven per cent of patients had missed a dose in the previous four days and 18 per cent in the previous two weeks. The main reason cited by patients for poor adherence was the fact that some patients had to pay a contribution to the cost of therapy. Researchers reporting to the Bangkok World AIDS Conference in 2004 found that in Haiti a programme of completely free access had resulted in 80% virological success, but a similar programme in Malawi where patients had to pay a contribution to medication was only 50% effective. As a result a group of health economists led by the South African Professor Alan Whiteside launched a campaign called ‘Free by 5’ in 2005 demanding free provision of ARVs to the developing world.
• Side-effects. ARV programmes in the developing world use fixed-dose generic combinations such as Triomune (d4T/3TC/nevirapine). D4T has largely stopped being used in the developing world due to its association with lipoatrophy (fat loss), and taking a fixed-dose combination containing nevirapine means patients cannot take a half-dose during the first two weeks in order to reduce the incidence of liver and skin reactions associated with this drug. One study in India (Pujari) found that lipoatrophy was detected in 26% of patients receiving d4T/3TC/nevirapine and 10% of those receiving AZT/3TC (p=0.08). Another study from Nigeria (Imarhiagbe) found that three out of eleven people given Triomune developed progressively higher triglyceride levels in their blood.

Progress towards HIV treatment – selected countries – June 2005 (unless stated)

What's next?

In July 2005 the G8 summit at Gleneagles announced the goal of universal HIV treatment access by 2010.

Funding will be crucially important to meet this goal

With UNAIDS calculating that the current cost of universal treatment, prevention and care for HIV being in the region of $27bn a year, but with the two largest funding mechanisms, the US Presidential Emergency Fund for AIDS Relief (PEPFAR) and The Global Fund for AIDS TB and Malaria, between then providing no more than $6bn a year, the international money to fight HIV/AIDS needs to be drastically upscaled if the epidemic is not to outrun the resources available to deal with it.

References

Blackstock O. Curing Stigma — The Limits of Antiretroviral Access. NEJM 353(8): 752, 2005.

Colebunders R et al. Free antiretrovirals must not be restricted only to treatment-naïve patients. PloS Medicine 2 (10): e276, 2005.

Health Systems Trust: South African Health Review 2005. See http://www.hst.org.za/publications/682

Imarhiagbe FA et al. Hypertriglyceridemia in Antiretroviral Therapy. Medscape General Medicine 7(3), 2005.

Kamya M.R. et al. Treatment outcomes for antiretroviral therapy in a routine clinical setting in Kampala, Uganda. Seventh International Congress on Drug Therapy in HIV Infection, Glasgow, abstract PL4.4, 2004.

Millennium Development Goals: see http://www.un.org/millenniumgoals/

Pujari SN et al. Lipodystrophy and dyslipidemia among patients taking first-line, World Health Organization-recommended highly active antiretroviral therapy regimens in western India. JAIDS 39: 199-202, 2005.

‘3 by 5’ campaign: see http://www.who.int/3by5/en/