HIV/AIDS – where are we now?

HIV/AIDS was one of the great issues of the late 20th century and, arguably, the issue in global health during that period.
Initially known as ‘gay-related immune deficiency’, the disease was soon renamed ‘acquired immune deficiency syndrome’ (AIDS), and we learned that it was caused by the human immunodeficiency virus (HIV). At first considered a death sentence, today HIV infection is manageable, with inexpensive and highly effective drugs. Australians living with HIV/AIDS now have a similar life expectancy to the rest of the population.

In this edition of In Brief, we present a brief history of HIV/AIDS, describe its current epidemiology in Victoria and Australia,
explain the state of the art in HIV/AIDS treatment and summarise the continuing challenges for researchers in this field.

A brief timeline of HIV/AIDS

1981	Neumocystis pneumonia (a rare lung infection) and Kaposi’s sarcoma (a rare and unusually aggressive cancer), were detected in young, previously healthy gay men in Los Angeles and New York, respectively. The United States Centers for Disease Control and Prevention (CDC) established a task force to examine risk factors and a case definition for surveillance.
1982	The term ‘acquired immune deficiency syndrome’ was used for the first time.
	The first case of AIDS in Australia (in an American tourist) was diagnosed in October.
1983	CDC noted that most AIDS cases were among homosexual men with multiple sexual partners, people who injected drugs, Haitians and haemophiliacs. CDC hypothesised that AIDS was caused by an infectious agent transmitted sexually or through exposure to blood or blood products, and issued recommendations for preventing transmission.
	In September, CDC identified all major routes of HIV transmission, ruling out casual contact, food, water, air or environmental surfaces as possible routes. In October, the World Health Organization (WHO) released its first assessment of the AIDS situation and began international surveillance.
	The first AIDS diagnosis in an Australian citizen was made in April 1983, and Australia’s first AIDS death occurred on 8 July.
1984	Dr Robert Gallo (United States National Cancer Institute) and Professor Luc Montagnier (Pasteur Institute) announced their independent identification of viruses that were the probable cause of AIDS.
1986	The agent that causes AIDS was officially named the human immunodeficiency virus.
	The first Australian needle and syringe program began in Darlinghurst, Sydney, in an informal trial of the measure’s ability to prevent HIV spreading among people who inject drugs.
1987	WHO launched The Global Program on AIDS to raise awareness, formulate evidence-based policies, provide technical and financial support, initiate research and champion the rights of people living with HIV. The first clinical trial of Azidothymidine (AZT) began, and later in 1987 it started to be used to treat HIV.
	The number of AIDS cases in Australia reached 745. Needle and syringe programs became official health policy in New South Wales. The infamous ‘Grim Reaper’ television advertisement, which used people being skittled with a bowling ball to represent the threat of HIV/AIDS, had its first screening on 5 April.
1988	WHO declared 1 December the first World AIDS Day. The Joint United Nations Programme on HIV/AIDS (UNAIDS) reported that more women than men in sub-Saharan Africa were living with HIV/AIDS.
	Australia’s 1000th AIDS notification occurred, as did its 500th death from AIDS since 1982.
1989	The number of reported AIDS cases in the United States reached 100 000.
1994	AIDS became the leading cause of death for all United States citizens aged 25 to 44 years.
1995	By year’s end, 49 AIDS cases had been reported in Australia.
1996	The annual number of new AIDS cases diagnosed in the United States declined for the first time since the beginning of the epidemic.
1997	Highly Active Anti-Retroviral Therapy, consisting of three or more anti-retroviral drugs, became the new standard of HIV care.
1999	WHO announced that HIV/AIDS had become the fourth biggest killer worldwide and the number one killer in Africa. An estimated 33 million people were living with HIV worldwide, and 14 million had died of AIDS.
2005	An estimated 40.3 million people worldwide were living with HIV/AIDS and 4.9 million people were newly infected.
2010	The first research showing that a daily dose of antiretroviral drugs reduced the risk of HIV infection among men who have sex with men by 44 per cent was released, supporting the concept of pre-exposure prophylaxis.
2012	The U.S. Federal Drug Administration approved the use of Truvada® for HIV prophylaxis. Adults could begin to take this medication to reduce their risk of HIV infection through sex.
2013	UNAIDS estimated that 2.3 million people were newly infected with HIV during the year; 1.6 million people died of AIDS; and 35.3 million people were living with HIV. Meanwhile, the number of new HIV infections fell more than 50 per cent in 25 low and middle-income countries, and the number of people getting antiretroviral treatment increased greatly.
2015	Researchers announced solid evidence that giving antiviral therapy to people with an undetectable viral load prevented HIV transmission to their sexual partners.
2016	The US National Institutes of Health and partners announced that a large trial of a candidate HIV vaccine would begin in South Africa in November.

HIV epidemiology in Australia

Annual HIV diagnoses in Australia peaked at 2412 in 1987, then fell steadily to 721 by 1999. Numbers then rose again to reach 1066 in 2012, and have been fluctuating around that mark ever since, with 1030 diagnoses in 2013, 1084 in 2014, 1027 in 2015 and 1013 in 2016. However, rapid population growth in Australia over the past decade means the population-based rate is trending downwards.

Male‑to‑male sex remains the major HIV risk exposure in Australia, accounting for 70 per cent of HIV diagnoses in 2016. Heterosexual sex accounted for 21 per cent of diagnoses, both male‑to‑male sex and injecting drug use for 5 per cent, and injecting drug use for 1 per cent.

An estimated 26 444 people were living with HIV in Australia in 2016. Of these, 95 per cent were in care, 86 per cent were receiving antiretroviral therapy and 93 per cent of those on treatment had an undetectable viral load, virtually eliminating the risk of onward HIV transmission.

HIV epidemiology in Victoria

Victorian HIV notifications have fluctuated around 300 per annum in recent years, totalling 302 in 2014, 283 in 2015, 320 in 2016 and 299 in 2017. However, as Victoria has experienced the strongest population growth of all Australian states and territories over recent years, at 2.4 per cent in 2016–17, the population-based HIV notification rate is trending downwards.

Just over half of all Victorian cases in 2017 were Australian-born (58 per cent); almost two thirds (60 per cent) of those born overseas were born in Asia. HIV continues to be most commonly diagnosed in Victorians aged 20 to 29 years (31 per cent in 2017).

Male-to-male sex was recorded as an exposure to HIV in 69 per cent of Victorian cases, compared to 76 per cent in 2016 and
77 per cent in 2015. Fourteen cases (4.6 per cent) reported only injecting drug use as their exposure to HIV in 2017, compared to three (0.9 per cent) in 2016 and nine (3.2 per cent) in 2015. The exposure category was unknown in 11 cases.

HIV prevention

HIV prevention began early in Australia due to a far-sighted bipartisan approach. In the mid-1980s former Labor health minister Neal Blewett and his Liberal–National Coalition counterpart, Dr Peter Baume, took a cooperative approach that was critical to containing HIV in Australia. It involved broadcasting public health messages, engaging priority groups (notably men who have sex with men), providing widespread education and information, promoting the use of condoms, reducing stigma and discrimination and a harm minimisation approach to drug use and HIV.

Needle and syringe programs

Australian governments invested $130 million in needle and syringe programs between 1991 and 2000, intending to reduce the sharing of used needles and syringes among people who inject drugs and, hence, transmission of HIV. This worked spectacularly well: HIV prevalence in people who inject drugs remains much lower in Australia than in countries in which needle-and-syringe programs (NSPs) began later, are less prevalent and less well resourced.

Australia’s investment in NSPs over the period 1991–2000 prevented an estimated 25 000 cases of HIV (and 21 000 cases of hepatitis C virus) among people who i nject drugs. The savings to the health system in avoided treatment costs over a lifetime were estimated at $2.4–$7.7 billion.

In June 2017, Australia had 98 primary NSPs (dedicated, standalone services), 784 secondary NSPs (services located in hospitals and health centres), 2422 pharmacies offering injecting equipment and 323 syringe-dispensing machines (mainly in NSW).
These outlets distributed 49 million needles and syringes in 2016/17.

Safeguarding the blood supply

Australia implemented universal HIV antibody screening of blood donors in early 1985, and only one case of HIV transmission by transfused blood has been recorded since. Before screening commenced, over 120 people (mainly haemophilia patients) who received clotting factors manufactured from donor plasma were infected with HIV.

The blood supply is safeguarded using a four-tiered approach:

Pre-donation public education via a website, mainstream media and the Blood Service National Contact centre. Donors are informed of eligibility criteria and the reasons for deferral from donation through brochures and handouts in collection facilities
Individuals who are at increased risk of blood-borne virus infection are excluded using screening questions prior to donation
All donated blood is tested to identify prospective donors with HIV and new infections in regular donors
Physical or chemical measures are applied to inactivate viruses and other infectious agents.

Testing

HIV testing became available in Australia in late 1984. Australian guidelines recommend that men who have sex with men (MSM) be tested for HIV at least annually. However, MSM who have unprotected anal sex, more than 10 sexual partners in six months, engage in group sex or use recreational drugs during sex should be tested up to four times per year.

In Victoria, both rapid tests and conventional blood tests for HIV are offered. A rapid HIV test involves a fingerprick blood sample and the result is available 10–20 minutes later. A conventional test involves a venous blood sample and laboratory testing, and results can take up to a week.

Prophylaxis

HIV pre-exposure prophylaxis (PrEP) is the regular use of HIV medications by HIV-negative people to prevent HIV acquisition. On 21 March 2018, the Federal Minister for Health announced that PrEP would be listed on the Pharmaceutical Benefits Scheme and therefore available by prescription through general practitioners (GPs). This decision made Australia one of the first countries with publicly funded universal access to PrEP.

Post-Exposure Prophylaxis (PEP) is a four-week course of anti-HIV drugs for people who suspect they have been exposed to HIV. PEP can prevent HIV infection if the treatment begins within 72 hours of exposure and is taken correctly over the following
28 days.

HIV treatment

Treatment with AZT alone (monotherapy) became available in 1987, but it soon became apparent that HIV became drug-resistant very rapidly due to its high mutation rate. Recognition of this led to the development of combination therapy, or highly active antiretroviral therapy (HAART), in 1996.

HAART involves multiple classes of antiretroviral drugs that prevent a single HIV strain gaining dominance. Initially, HAART required HIV patients to take multiple pills every day. Significant toxicity and side effects soon became apparent, including lipodystrophy (fat redistribution and serum lipid/glucose abnormalities), insulin resistance, and peripheral neuropathy.

Continual improvements in HAART mean that HIV is now considered a chronic but manageable health condition. HAART now involves (for some people) taking a single pill each day. Treatment can lead to an undetectable viral load, meaning virtually no risk of transmission and no disease progression.

Research challenges

A vaccine remains the holy grail of HIV research. Many HIV vaccines have been tested already; a vaccine trialled in Thailand in 2009 showed some protective effect (31 per cent effectiveness), but too little to warrant roll-out.

Researchers worldwide are working on both preventive and therapeutic vaccines. Two HIV vaccine candidates are currently being trialled. A Phase III trial called HVTN 702 aims to enrol 5400 South African men and women to test a vaccine against the most common HIV subtype in southern Africa. A second trial, called HPX2008/HVTN 705, will enroll 2600 women in five countries across sub-Saharan Africa, and is aimed at eliminating multiple HIV subtypes.

Conclusion

HIV/AIDS has evolved from a major and rapidly expanding disease threat to a relatively stable pandemic, and from a death sentence to a manageable chronic disease. The next few years will show whether HIV vaccines, in combination with treatments, prevention and prophylaxis, are capable of ending the HIV pandemic.