How does antiretroviral treatment work?
Drugs used to treat HIV, known as antiretrovirals or antiretroviral therapy (ART), prevent HIV from replicating and infecting new immune system cells in the body. ART therefore reduces the levels of HIV in an individual’s body to extremely low levels as well as preventing damage to his or her immune system. In contrast, when HIV is left untreated, it is the depletion of immune function that leaves the body vulnerable to a wide range of infections and which eventually leads to serious illness and death.
Individuals who are diagnosed soon after HIV infection and begin ART without delay are able to remain in good health for decades, with a life expectancy similar to that of people who don’t have HIV.1 However, less than half of people living with HIV in the world have good enough access to high quality health services for that potential to be realised.
Global uptake of treatment
Of the 37 million people living with HIV, only 41% of adults and 32% of children living with HIV were receiving ART in 2014.2
Nonetheless these figures are highly impressive when compared with those of only a few years ago. In 2002 the World Health Organisation (WHO) announced a plan that appeared to some at the time to be over-ambitious - their 3 by 5 initiative aimed for three million people to be on treatment by 2005. It accelerated access to treatment (to 2.2 million people) without quite meeting its objective in time.
The movement then gained momentum, with 7.5 million people receiving treatment in 2010. By the middle of 2015, 15.8 million people were receiving HIV treatment.3
Men are less likely than women to receive treatment; children and adolescents are also underserved.4 Although the availability of treatment has improved in all parts of the world, the proportion of people living with HIV receiving ART varies considerably between regions. There are particular gaps in low- and middle-income countries, especially those in Eastern Europe and the Middle East.5
However, as the burden of HIV is concentrated in a few key countries, improvements in the availability of treatment in specific countries can have a significant impact on the overall global situation. For example, South Africa has the largest population of people living with HIV in the world (6.9 million). A radical turn-around in its government’s health policy resulted in the number of South Africans receiving treatment jumping from 4,000 to 3.1 million between 2000 and 2014. The country now has the largest HIV treatment programme in the world.6
Globally, 61% of all people with HIV live in just ten countries – South Africa, Nigeria, India, Kenya, Mozambique, Uganda, Tanzania, Zimbabwe, the United States of America, and Zambia.7 While this means that efforts can be focused, these are mostly low-income countries, adding to the challenge.
Ambitious targets and guidelines
Despite rapid progress, the Joint United Nations Programme on HIV and AIDS (UNAIDS) and the World Health Organisation (WHO) have set global targets that are far more ambitious.
UNAIDS is encouraging countries to work towards targets known as 90-90-90.8 The aim is that by 2020, 90% of all people living with HIV will know their status, 90% of those diagnosed will be on treatment, and 90% of those on treatment will be virally suppressed (where the level of HIV in the blood is below 200ml, indicating successful treatment). This would mean that 73% of the global population of people living with HIV would be virally suppressed by 2020. If this is achieved, then models predict the end of HIV as an epidemic disease by 2030.
Consistent with those targets, the World Health Organisation now recommends that everybody living with HIV, of all ages and in all parts of the world, should receive antiretroviral therapy.9
Previously, guidelines were more cautious, only recommending treatment to certain groups – for example, individuals with a more depleted immune system (as shown by clinical symptoms or a lower CD4 cell count), people with tuberculosis co-infection or pregnant women who needed to prevent transmission to an unborn child. However the evidence of the benefit of prompt HIV treatment for all has now become overwhelming. Studies have conclusively demonstrated that delaying HIV treatment10 and taking breaks11 from HIV treatment results in greater morbidity and mortality. Research has also shown that effective HIV treatment prevents onward transmission to sexual partners12 and unborn children.
The guidelines have therefore become simpler. WHO recommends that all people living with HIV should begin antiretroviral therapy as soon as possible after diagnosis and continue to take it indefinitely. Assessment of an individual’s clinical stage or CD4 cell count is not required before initiating HIV treatment.
Nonetheless in situations where resources prevent full implementation of the guidelines, treatment should be prioritised for individuals with severe or advanced HIV clinical disease (WHO clinical stage 3 or 4) and individuals with a CD4 cell count below 350 cells/mm3. This is to ensure that people who urgently need treatment are not displaced by people whose need is less pressing.
Achieving the targets
These changes to the treatment guidelines dramatically affect the scale of HIV treatment programmes – and the financial resources required. An analysis based on 2014 figures showed that if only those with a CD4 cell count below 200 were eligible for treatment (as had been recommended in 2002), then 11 million people would need treatment. Based on the 2010 recommendation to offer treatment to those with a CD4 cell count below 350, 15 million require treatment. With 2013’s shift to recommend treatment for all those below CD4 500, 28 million require treatment. Finally, with the 2015 recommendation for treatment for everyone diagnosed, almost 37 million need antiretroviral therapy.14
Only a limited number of countries (all upper-middle-income or high-income) have updated their national guidelines to recommend treatment for all.15 This means that treatment is usually only begun when patients already have a low CD4 cell count and a weakened immune system. As a result their medical care is often more complicated and expensive. Delaying treatment also contributes to extra HIV infections – increasing future costs - as the potential of earlier treatment to prevent onward transmission has been missed.16
With the global burden of HIV concentrated in low and lower-middle income countries, funding from international donors has been essential to the scale-up of HIV treatment. The contribution of the American government, primarily channelled through the President’s Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, Tuberculosis and Malaria, has been particularly important.
A rapid scale-up of international funding from $1.2 billion in 2002 to $7.8 billion in 2008 allowed many countries’ treatment programmes to expand in that period.17 But international donors have curtailed or capped their contributions since the 2008 financial crash. With $8.6 billion provided in 2014, funding is little different to that available six years earlier. A scale-up in line with either WHO treatment guidelines or UNAIDS’ 90-90-90 targets is extremely challenging in this context.18
In response, funding from domestic governments has become increasingly important for HIV programmes in many countries. By 2014, domestic funding comprised about 57% of total resources available for HIV programmes in low- and middle- income countries. In the five previous years, 84 countries increased their domestic spending on AIDS, including 35 which more than doubled it.19
Such shifts are dependent on countries’ economic growth and on political leadership. In too many countries, leaders are unwilling to fully support HIV programmes or they limit their support to specific elements. Provision for key affected populations such as sex workers or people who inject drugs is often seen as politically unpalatable.
Drug prices and generics
While staffing and infrastructure costs are important, the biggest single element influencing the affordability of HIV treatment programmes is the price of antiretroviral drugs. Generic manufacturers now supply more than 95% of all ARVs in low- and middle- income countries, at a cost of less than US$ 150 per person per year for a person’s first treatment regimen.20 But if a person needs to switch to an alternative regimen, its price may be around $300 a year and third-line regimens (rarely available from generic manufacturers) may cost 15 times more than the standard first-line regimen. Further patent restrictions and a weakening of competition from generic manufacturers could restrict access to newer medicines.
Moreover economic growth in many countries may move them into the middle-income bracket, meaning that they are no longer permitted to use generic drugs and may also become ineligible for international donor funding.
Weak healthcare systems
The effective scale-up of HIV treatment is made more challenging by weak health services and health systems in many countries. In places where health services are difficult to access, understaffed or poorly organised, uptake of testing and treatment is suboptimal, with too many people dropping out of care when faced with difficulties.
A very concrete example is stock-outs, when antiretrovirals or other medical supplies cease to be available in clinics. Poor planning, forecasting and budgeting; delivery delays; and corruption are described as the most common reasons for stock-outs.21 When stock-outs occur, individuals may simply take a forced break from their treatment and wait for supplies to be replenished, risking the development of drug resistance, treatment failure and a switch to a more expensive drug combination.
Improving access to treatment
The role of civil society
Civil society movements have been vital in placing HIV high up on the public health agenda and in finding solutions to challenging problems. Further pressure from civil society may be needed for the next scale-up of treatment to be achieved.
To look at an historical example, South Africa’s treatment access movement linked street protests and community activism with court challenges and high-level lobbying.22 Campaigners focused on social justice and linked with activists across the world, ultimately achieving a relaxation of intellectual property restrictions. Campaigning eventually led to a change in the South African government’s approach to HIV and the world’s largest HIV treatment programme.
The changing role of healthcare providers
Activism has also spurred innovations in the health sector. For example, ‘task-shifting’ involves redistributing human resources so that, for example, a nurse rather than a doctor initiates patients on antiretroviral therapy. This means that shortages of qualified doctors do not stop people from receiving treatment as nurses can be trained for specific tasks and are less costly.
People living with HIV have also been involved in delivering care to their peers – sometimes as a counsellor, but sometimes with a more extensive role. For example rather than requiring patients to make a lengthy visit to the clinic each month, they may be seen inbetween clinic visits by a trained peer who assesses adherence and conducts basic health checks, referring patients to the clinic in the case of any abnormalities.23 In southern Africa, patients who are stable on therapy sometimes form groups in which members distribute medication to each other.24
Such projects particularly respond to the challenge of an ever increasing number of people who are stable on HIV treatment and will need an ongoing supply of ARVs for the rest of their lives.25 Without innovation, they will fill up existing health facilities and reduce capacity for patients who are unwell or newly diagnosed.
‘Decentralisation’ of HIV care to a wider range of health services can also make HIV treatment more accessible. HIV treatment may be integrated with services for tuberculosis, maternal and child health, hepatitis, or other health conditions. For example South Africa made ART available at virtually every public health facility in the country.26
Improving the efficiency of treatment services will mean that more patients can be treated for the same financial resources. Wide variations in the cost of providing treatment between facilities demonstrate that some facilities are less efficient whereas others may be benefiting from economies of scale (providing ART to more patients while fixed costs remain the same) or economies of scope (integrating ART delivery with other health services). Other efficiency gains are possible through improving procurement systems so as to lower the cost of commodities and introducing new technologies (such as point-of-care diagnostic tests).27
Addressing stigma and discrimination
Finally, addressing the stigma and discrimination faced by people living with HIV – especially that which occurs in health services - may encourage more people to test and to start treatment. Many people living with HIV, especially those who belong to key populations such as people who use drugs or men who have sex with men, report stigmatising attitudes from health workers which discourage them from using health services. Revising laws which discriminate against key populations, protecting the rights of people living with HIV and making legal services available so that people can seek redress may ultimately have an impact on the uptake of antiretroviral therapy.
Photo credit: ©AVERT by Corrie Wingate. Photos are used for illustrative purposes. They do not imply any health status or behaviour on the part of the people in the photo.
- 1. Sabin, C.A., (2013) 'Do people with HIV infection have a normal life expectancy in the era of combination antiretroviral therapy?' BMC Medicine 11:251
- 2. UNAIDS (2015) 'Fact sheet 2015'
- 3. UNAIDS (2015) 'On the Fast-Track to end AIDS by 2030: Focus on location and population'
- 4. UNAIDS (2015) 'On the Fast-Track to end AIDS by 2030: Focus on location and population'
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- 9. World Health Organization (2015) 'Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV'
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- 11. SMART Study Group (2006) 'CD4+ count-guided interruption of antiretroviral treatment' New England Journal of Medicine 30;355(22):2283-96
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- 14. D Cooper (2015) 'Antiretroviral Therapy: Past, Present, and Future' 2015 Conference on Retroviruses and Opportunistic Infections, Seattle, N’Galy-Mann Lecture
- 15. Health GAP (2015) 'Towards Treatment on Demand for All'
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- 17. Kaiser Family Foundation and UNAIDS (2015) 'Financing the Response to AIDS in Low- and Middle-Income Countries: International Assistance from Donor Governments in 2014'
- 18. Dutta A et al (2015) 'The HIV Treatment Gap: Estimates of the Financial Resources Needed versus Available for Scale-Up of Antiretroviral Therapy in 97 Countries from 2015 to 2020'. PLOS Medicine Nov; 12(11): e1001907
- 19. UNAIDS (2015) 'How AIDS changed everything: MDG 6: 15 years, 15 lessons of hope from the AIDS response'
- 20. World Health Organization (2015) 'Global health response to HIV, 2000-2015, focus on innovations in Africa'
- 21. International Treatment Preparedness Coalition (2014) 'Global policy, local disconnects: a look into the implementation of the 2013 HIV treatment guidelines'
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- 23. Selke HM et al (2010) 'Task-Shifting of Antiretroviral Delivery From Health Care Workers to Persons Living With HIV/AIDS: Clinical Outcomes of a Community-Based Program in Kenya' JAIDS 55:4
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- 27. PEPFAR (2011) 'PEPFAR: Making Smart Investments to Increase Impact and Efficiency and Save More Lives'