HIV @ 25:HAART @ 10
It’s 25 years since HIV came to light,
and despite treatments, more new infections and deaths occurred last year
than ever before. Robert Fieldhouse looks back and chats
to people living with HIV about their future hopes
Photos Piers Allardyce
On
5 June, 1981, the US Centers for Disease Control and Prevention issued its
first warning about
a rare form of pneumonia in five previously healthy, young gay men in Los
Angeles. These men were later acknowledged to be the first reported cases
of a disease that would change the world for ever, a disease that in time
would become known as acquired immunodeficiency syndrome, or Aids.
Summer 1981 may be the beginning of Aids as we know it, but the oldest specimen
of HIV in a blood sample dates back to 1969, from a man in the Congo. The
first Aids cases in Africa were reported in 1982, just one year after those
in the States. In 1983 a virus, HIV, was isolated in a person with Aids, establishing
a viral cause for the immune deficiency. Aids was to quickly become, and is
still today, one of the greatest global public health challenges ever known
to man. In 25 years HIV has claimed the lives of more than 25 million people
worldwide. An estimated 65 million have become HIV positive, and 40 million
are thought to be living with the virus today.
A global response
From the outset, countless individuals and organisations mobilised collectively
to respond, provide prevention and care services, and develop treatments.
The involvement of those affected by the disease strengthened this response.
Men and women living with HIV have over the past quarter century demonstrated
commitment and dedication in the face of adversity and stigma.
The first decade of Aids was particularly challenging, defined proudly by
activism borne of anger, loss and discontent; by a struggle for recognition,
for answers, for treatment. The advent of effective treatments ten years ago
challenged accepted ways of thinking about Aids and the fight-back stepped
up a gear.
People afforded the privilege of access to treatments, because of where they
were born or where they lived had, for the first time, real hope of survival.
Early media reports of the success of protease inhibitors described the response
to the new therapies using overblown, Biblical allusions; “the Lazarus
complex” it was often called. That said, compared to the treatments
previously available until that point, the results were pretty amazing.
A lot has changed in ten years: more people have been diagnosed HIV positive
in the UK year-on-year since the late 1990s. And yet too high a proportion
in this country (around a third) still remain undiagnosed, effectively denying
themselves access to treatments. But the number receiving therapy in countries
like the UK has increased exponentially in the past ten years. Estimates suggest
over 30,000 people are now on treatments in the UK.
For many people in the developed world, HIV has become more manageable. But
people are still diagnosed too late; still refuse treatment, and, in the UK,
still refused special leave to remain on medical grounds. And people are still
dying. The UK government pumps money abroad to expand access to prevention
and treatment services, but the Home Office still mercilessly sends people
from abroad home to die. One unparalleled success in public health is our
ability to prevent mother-to-child HIV transmission with timely HIV diagnosis
and initiation of antiretroviral therapy.
Paul Jackson
Diagnosed: 1998, with cryptococcal meningitis.
HAART history: I started immediately with a protease inhibitor. I’ve
switched four times. I now take tenofovir/nevirapine/3TC. My CD4 is now 380
and I’ve been undetectable for five years.
Hopes: To have a great love life.
Life before HAART
The first antiretroviral, AZT, was approved for use in adults in the US in
1987, paediatric licensing followed in 1990. Its manufacturer Burroughs Wellcome
attached an extortionate price tag but ACT UP (AIDS Coalition to Unleash Power)
was established in New York to challenge the cost and the price was subsequently
lowered. For a few years there was just AZT and nothing else.
Guidelines on how to prevent the opportunistic infection pneumocystis carinii
pneumonia (PCP) were published. Over time other drugs which work in the same
way as AZT became licensed and dual HIV therapy (combining two nucleoside
analogues) was shown to be more potent than single therapy.
Munisimenda Kanyama
Diagnosed: 2003, with a CD4 count of nine.
HAART history: I started immediately with Combivir/efavirenz, but changed
to Combivir/nevirapine. I’m now taking Kivexa/nevirapine. Once daily
therapy is more manageable. I now sleep well and my sex drive has returned
to normal.
Hopes: To be able to access medication when I go back home to a country which
has one million people living with HIV, and only 33,000 people receiving antiretrovirals.
Raising the bar
Saquinavir was the first of a new class of antiretroviral drugs called protease
inhibitors (PIs) to be licensed in 1994. Its significance as a new treatment
is highlighted by the fact that Roche, its manufacturer, received approval
for the drug in the USA in a record 93 days.
From now on the bar was raised. Clinical trials of other PIs began enrolling
and the Vancouver Aids Conference of 1996, where the results of those early
protease inhibitor studies were presented, became synonymous with highly active
antiretroviral therapy (HAART). For the first time, combinations of HIV drugs
were shown to raise people’s CD4 counts for longer periods of time and
a new test that became an essential HIV management tool, viral load testing,
demonstrated the virus could be reduced to ‘undetectable’ levels,
that is, below the level of the detection of the test. Initial hopes that
a few years of fully suppressive therapy would cure HIV soon faded, as the
virus was shown to hide in sanctuary sites at a very low level, only to re-emerge
should the drugs be taken away. But Aids cases and death declined dramatically
in countries with access to these drugs.
Thomas Marsh
Diagnosed: in 2002, with a CD4 of 250.
HAART history: I started with Combivir and efavirenz in 2002. I recently switched
to Kivexa and efavirenz last year. My CD4 is now over 500.
Hopes: To feel more confident about disclosing my HIV status, especially with
a potential employer.
Grapefruit juice and fasting
Early protease inhibitors (PIs) were difficult to take, multiple tablets taken
three times a day. The first formulation of saquinavir had to be taken with
high-fat food and grapefruit juice to boost its levels, whereas the alternative
PI, indinavir, demanded that you starved yourself three times a day and drank
litres of water to try to reduce the development of painful kidney stones.
People did as they were told because there was little choice.
Tom Matthews
Diagnosed: 1986, with a CD4 count of 720.
HAART history: Now taking abacavir/3TC and nelfinavir.
Hopes: Two years ago I began to seriously acknowlege that I have a future
after eight years of being undetectable. I’m retraining as a counsellor.
It’s a good opportunity to have a third career. HIV has added a completely
new dimension to my life.
Ritonavir-boosting PIs
By the end of the 1990s, it was clear the potency and formulation concerns
of early PIs could be overcome by boosting them with a low dose of another
PI, ritonavir. This cut dosing from three times to two times a day and allowed
the dietary restrictions to be relaxed. Eventually the PI lopinavir became
available with ritonavir included, avoiding the need to take additional ritonavir
capsules. Newer PIs such as atazanavir appear more lipid-friendly than the
drugs of old.
Melanie McKay
Diagnosed: 1986, aged eight, after receiving blood transfusions between the
ages of three and five.
HAART history: I took AZT alone for eight years, then switched to ddI/ddC.
My first triple combination contained the PI nelfinavir. I’ve been taking
T-20, tenofovir, and atazanavir/ ritonavir for a year now. My energy levels
are sky high: I don’t need to sleep, my viral load is undetectable and
my CD4 count is recovering.”
Hopes: To continue volunteering at SHIELD in Sheffield.
Arrival of non-nukes
As some researchers were developing PIs, others found different kinds of drugs
to fight HIV. The class destined to become first choice treatment for the
majority was the
NNRTIs (non-nucleoside reverse transcriptase inhibitors). Two drugs from this
family, nevirapine and efavirenz, have been the mainstay of therapy since
the late 1990s. These are simpler to take than PIs and are of comparable potency
to a boosted PI.. Efavirenz, along with 3TC and AZT became the first combo
to out-perform a protease combo in a large clinical trial, establishing a
new treatment paradigm.
Beatrice Nabulya
Diagnosed: 1992, with a CD4 count of 200.
HAART history: I took AZT on its own during pregnancy. I’ve taken Combivir
and nevirapine and abacavir/AZT/3TC. I’m now taking Kivexa/efavirenz.
Hopes: I hope there’ll be a medication I can take once a month. I’m
grateful that therapy kept my children healthy. I’m still here when
all my family back home are dead.
Combining drugs into one pill
To make meds easier to take, drug companies experimented with the idea of
putting more than one drug in a single pill. GlaxoSmithKline developed Combivir,
combining AZT and 3TC, halving the daily dose to one pill, twice a day. The
three-in-one Trizivir (AZT/3TC/abacavir) followed. Currently most people starting
therapy have the choice between two other co-formulations: Kivexa (abacavir/3TC)
or Truvada (tenofovir/FTC). Soon we may have a new, three-in-one pill (tenofovir/FTC/efavirenz),
which will provide many with the prospect of just one pill, once a day.
Angelina
Namiba
Diagnosed: many years ago!
HAART history: I took AZT alone twice during pregnancy. I started treatment
last year with lopinavir/ritonavir and Combivir. Starting treatment was like
being diagnosed all over again. What has treatment given me? Lots of diarrhoea!
Hopes: To see my daughter grow, to stay well, and to
continue challenging the stigma and myths that surround women living with
HIV.
…and the fall of AZT and d4T
Most people starting therapy began with one of the two ‘thymidine’
nucleoside analogues (AZT or d4T). But with long-term use a significant proportion
of people taking these drugs developed fat loss. Though it occurs more quickly
and in a greater proportion of people using d4T, than AZT.
Nukes licensed after AZT and d4T, particularly abacavir and tenofovir, are
less likely to cause fat loss, and this is one reason many people starting
therapy today will choose one of these. Side effects remain the major reason
people switch from their first treatment.
Mark Pannick
Diagnosed: 2001 with CD4 of 822.
HAART history: I started therapy in 2005, with lopinavir/ritonavir and Truvada.
My CD4 is currently 518.
Hopes: I feel very positive about the future. I am studying computers and
volunteering on the UKC events team.
Nevirapine: a drug for the world
It’s hard to pick one drug from the 25 or so available in the UK that
meets all our needs, and no drug is right for everyone, but the NNRTI nevirapine
comes pretty close. Many of the people featured in this issue have taken nevirapine
in the past or are currently taking it.
What is it we are actually looking for? Simplicity: just one pill, twice a
day, though an increasing proportion of people now take it once-daily with
their doctor’s permission (though remember it’s unlicensed for
once daily use). Tolerability: it has a favourable side effect profile, if
used by men with CD4 counts less than 400 and women with CD4 counts less than
250 cells. It’s lipid-friendly and does not seem to contribute to body
fat changes. Potency: a clinical trial of over 1,000 patients starting therapy
demonstrated it to be as potent as the alternative, efavirenz.
Nevirapine was licensed in 1996, so it, like HAART, is now ten years old.
There are now close to one million years of patient experience with this drug
and there’s a safety in taking drugs we’ve had licensed for years
as we’re unlikely to now witness any new toxicity.
The World Health Organization (WHO) favours the classic combination of nevirapine
(with d4T and 3TC) for most starting therapy in the developing world. Around
1.3 million people are estimated to be receiving therapy in developing countries
and at least half of these take nevirapine.
The WHO used many of the sites where the nevirapine donation programme took
place to roll out access to antiretrovirals in its 3x5 initiative, so the
drug has been instrumental in the development of an infrastructure to attempt
to create access for all.
Nevirapine also plays a key role in global prevention of mother-to-child transmission
programmes, although it is unlicensed for this use. Around three-quarters
of a million mother-baby pairs have been treated with it in Africa, eastern
Europe and South and Central America. The WHO recommends preventive combination
therapy using AZT and nevirapine with 3TC, (to reduce the risk of nevirapine
resistance) as the most effective standard regimen for pregnant women. However,
it’s also recognised these regimens might not be available or feasible
in all settings. In such cases, a single-dose of nevirapine should be offered
to the mother at the onset of labour, and to the baby within 72 hours of birth.
Silvia
Petretti
Diagnosed: 1997 with CD4 of 358.
HAART history: I started with ddI, 3TC, indinavir/ritonavir in 1998 but changed
to nevirapine and Combivir. I had to switch to efavirenz. I recently switched
to lopinavir/ritonavir, tenofovir and ddI as I toyed with the idea of getting
pregnant. My CD4 is now 340, the highest its been for years”.
Hopes: Continue as an activist to make life for recently diagnosed women better
than mine was. I’m still waiting for my knight in shining armour. I’ve
got hep C coinfection, but my daily yoga has restored my
energy to better-than-normal levels.
The future
New drugs that work in completely different ways to current antiretrovirals
are on the horizon.
PN asked Dr Mike Youle, director of HIV clinical research at London’s
Royal Free Hospital, to sum up where we’re at with HIV treatment: “HAART
has revolutionised and normalised HIV therapy in the past ten years and the
next ten look even better with simpler regimens and safer drugs. Now it remains
the responsibility of patients to take their therapy and for doctors and nurses
to continue to use the best available agents to reduce side effects and give
the best results and the NHS to adequately fund these effective therapies.”
We owe it to the people without access, and those who have died before the
advent of HAART to make sure we all continue to play our part.
