2
MILESTONES IN THE ERA OF EFFECTIVE HIV TREATMENT The first HIV med, Retrovir (zidovudine, or AZT), was approved in 1987. Over the next few years, additional antiretrovirals (ARVs) were introduced in the same drug class (nucleoside reverse transcriptase inhibitors, also known as NRTIs, or nukes). But using only one or two meds from the same drug class wasn’t enough to fully suppress the virus, and the crisis period of the epidemic raged on. In December 1995, the first protease inhibitor (PI), Invirase (saquinavir), was approved, and a new era of combination therapy was set to begin. Here’s a timeline of the highlights: At the 11th International AIDS Conference in Vancouver, numerous studies demonstrate the efficacy of triple-combination antiretroviral (ARV) treatment, ushering in the era of what was then called highly active antiretroviral treatment, or HAART. The first viral load test is approved. The first non- nucleoside reverse transcriptase inhibitor (NNRTI, or non-nuke), Viramune (nevirapine), is approved. 1996 1997 1998 2001 2002 2003 2006 2007 2008 2010 2011 2012 2013 2014 2015 The first combination ARV tablet, Combivir (zidovudine/ lamivudine), is approved. AIDS-related deaths drop 47 percent in one year. The Global Fund to Fight AIDS, Tuberculosis and Malaria in developing nations is launched. President George W. Bush launches the U.S. President’s Emergency Plan for AIDS Relief, or PEPFAR, pledging to spend $15 billion to combat the disease in poorer nations in five years. The first once-daily, single-tablet ARV regimen, Atripla (efavirenz/TDF/ emtricitabine), is approved. The SMART trial is stopped early. The expansive global study investigated whether interrupting HIV treatment could reduce the risk of diseases thought to be the result of ARV toxicities. But those who interrupted treatment actually had worse health outcomes. The surprise findings spur research into the link between HIV, chronic inflammation and non-AIDS- defining conditions such as heart disease. The first integrase inhibitor, Isentress (raltegravir), is approved. The first oral entry inhibitor, Selzentry (maraviroc), is approved. As HIV treatments improve, U.S. treatment guidelines up the CD4 threshold for starting ARVs to 350. As San Francisco recommends HIV treatment regardless of CD4 count, U.S. guidelines advise starting ARVs when CD4s drop to 500, while the threshold set by the World Health Organization (WHO) is 350 CD4s. The HPTN 052 study finds that starting ARVs reduces the risk of transmitting HIV through heterosexual sex by 96 percent, launching the treat- U.S. guidelines recommend treatment for all people living with HIV, regardless of their CD4 count. The FDA approves Truvada (TDF/ emtricitabine) for use as pre-exposure prophylaxis (PrEP). UNAIDS reports that global AIDS- related deaths have fallen 30 percent since peaking in 2005. WHO recommends treatment once CD4s hit 500 or below. Interim results from the ongoing PARTNER study find that there have been no transmissions between partners in gay or straight mixed-HIV-status couples in which the HIV-positive partner has an undetectable viral load. Researchers estimate that the actual transmission risk may be close to zero, or in fact zero. The placebo arm of the global START trial is terminated early when it becomes clear that there is a lower risk of various negative health outcomes associated with starting ARVs when CD4s are above 500 compared with waiting until they hit 350. In response, WHO supports treatment for all, regardless of CD4 count. Genvoya (elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide, or TAF) is the first approved combination tablet to include an updated version of tenofovir that is safer for bones and kidneys. ment-as-prevention (TasP) era. The FD approve Truv uvad a a (TD emtr tric i itabin fo or use a pre-ex exposu prop ophy h lax (P (PrEP Gen (elv cob emt teno alaf or T The U.S. Department of Health and Human Services issues the first federal HIV treatment guidelines, recommending treatment for those with fewer than 500 CD4s, in keeping with the “hit early, hit hard” philosophy of the time. Viread (tenofovir disoproxil fumarate, or TDF), which comes with bone and kidney toxicities, is approved and goes on to become the most widely prescribed ARV. ALL IMAGES: ISTOCK (MODELS USED FOR ILLUSTRATIVE PURPOSES ONLY) In an about-face, U.S. treatment guidelines switch to recommending starting ARVs when CD4s have dropped to 200 or below. 1 9 9 9 9 9 9 6 6 the pa u e t 1999 2000 2004 2005 2009 The first entry inhibitor, the injectable Fuzeon (enfuvirtide), is approved. Norvir (ritonavir), a PI that would become a booster of other ARVs, is approved.

MILESTONES IN THE ERA OF EFFECTIVE HIV TREATMENT · MILESTONES IN THE ERA OF EFFECTIVE HIV TREATMENT Thfi rst HIV med, Retrovir (zidovudine, or AZT), was approved in 1987. Over the

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Page 1: MILESTONES IN THE ERA OF EFFECTIVE HIV TREATMENT · MILESTONES IN THE ERA OF EFFECTIVE HIV TREATMENT Thfi rst HIV med, Retrovir (zidovudine, or AZT), was approved in 1987. Over the

MILESTONES IN THE ERA OF EFFECTIVE HIV TREATMENTThe fi rst HIV med, Retrovir (zidovudine, or AZT), was approved in 1987. Over the next few years, additional antiretrovirals (ARVs) were introduced in the same drug class (nucleoside reverse transcriptase inhibitors, also known as NRTIs, or nukes). But using only one or two meds from the same drug class wasn’t enough to fully suppress the virus, and the crisis period of the epidemic raged on. In December 1995, the fi rst protease inhibitor (PI), Invirase (saquinavir), was approved, and a new era of combination therapy was set to begin. Here’s a timeline of the highlights:

At the 11th International AIDS Conference in Vancouver, numerous studies demonstrate the effi cacy of triple-combination antiretroviral (ARV) treatment, ushering in the era of what was then called highly active antiretroviral treatment, or HAART.

The fi rst viral load test is approved.

The fi rst non-nucleoside

reverse transcriptase

inhibitor (NNRTI, or non-nuke),

Viramune (nevirapine), is

approved.

199

6

199

7

199

8

20

01

20

02

20

03

20

06

20

07

20

08

20

10

20

11

20

12

20

13

20

14

20

15

The fi rst combination ARV tablet, Combivir (zidovudine/lamivudine), is approved.

AIDS-related deaths drop 47 percent in one year.

The Global Fund to Fight AIDS, Tuberculosis and Malaria in developing nations is launched.

President George W. Bush

launches the U.S. President’s

Emergency Plan for AIDS Relief,

or PEPFAR, pledging to

spend $15 billion to combat the

disease in poorer nations in fi ve years.

The fi rst once-daily, single-tablet ARV

regimen, Atripla (efavirenz/TDF/

emtricitabine), is approved.

The SMART trial is stopped early. The expansive global study investigated whether interrupting HIV treatment

could reduce the risk of diseases thought to be the

result of ARV toxicities. But those who interrupted

treatment actually had worse health outcomes.

The surprise fi ndings spur research into the

link between HIV, chronic infl ammation and non-AIDS-

defi ning conditions such as heart

disease.

The fi rst integrase inhibitor, Isentress (raltegravir), is approved.

The fi rst oral entry inhibitor, Selzentry (maraviroc), is approved.

As HIV treatments improve, U.S. treatment guidelines up the CD4 threshold for starting ARVs to 350.

As San Francisco recommends HIV treatment regardless of CD4 count, U.S. guidelines advise starting ARVs when CD4s drop to 500, while the threshold set by the World Health Organization (WHO) is 350 CD4s.

The HPTN 052 study fi nds that starting

ARVs reduces the risk of transmitting HIV

through heterosexual sex by 96 percent,

launching the treat-ment-as-prevention

(TasP) era.

U.S. guidelines recommend treatment for all people living with HIV, regardless of their CD4 count.

The FDA approves

Truvada (TDF/emtricitabine)

for use as pre-exposure

prophylaxis(PrEP).

UNAIDS reports that global AIDS-related deaths have fallen 30 percent since peaking in 2005.

WHO recommends

treatment once CD4s hit 500 or below.

Interim results from the ongoing

PARTNER study fi nd that there have been

no transmissions between partners

in gay or straight mixed-HIV-status

couples in which the HIV-positive

partner has an undetectable

viral load. Researchers

estimate that the actual

transmission risk may

be close to zero, or in fact zero.

The placebo arm of the global START trial is terminated early when it becomes clear that there is a lower risk of various negative health outcomes associated with starting ARVs when CD4s are above 500 compared with waiting until they hit 350. In response, WHO supports treatment for all, regardless of CD4 count.

Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, or TAF) is the fi rst approved combination tablet to include an updated version of tenofovir that is safer for bones and kidneys.

ment-as-prevention (TasP) era.

The FDapprove

Truvuvadada (TDemtrtrici itabin

fofor use apre-exexposu

propophyhylax(P(PrEP

Gen(elvcobemttenoalafor T

The U.S. Department of Health and Human Services issues the fi rst federal HIV treatment guidelines, recommending treatment for those with fewer than 500 CD4s, in keeping with the “hit early, hit hard” philosophy of the time.

Viread (tenofovir disoproxil

fumarate, or TDF), which comes

with bone and kidney toxicities, is approved and

goes on to become the most widely prescribed ARV.

ALL IMAGES: ISTOCK (MODELS USED FOR ILLUSTRATIVE PURPOSES ONLY)

In an about-face, U.S. treatment

guidelines switch to recommending

starting ARVs when CD4s have dropped

to 200 or below.

1999999

66

the pa

u

e

t

199

9

200

0

20

04

20

05

20

09

The fi rst entry inhibitor, the injectable Fuzeon (enfuvirtide), is approved.

Norvir (ritonavir),

a PI that would become

a booster of other ARVs, is

approved.

P07-16_Insert_Timeline_HY.indd 1 6/2/16 12:36 PM

cocobememte

or T

9996

pa

ee

ment-as-prevention

The fi rst entry

era.

GenGen

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POZ14477-00_GatefoldInsert.pgs 06.02.2016 12:39

Page 2: MILESTONES IN THE ERA OF EFFECTIVE HIV TREATMENT · MILESTONES IN THE ERA OF EFFECTIVE HIV TREATMENT Thfi rst HIV med, Retrovir (zidovudine, or AZT), was approved in 1987. Over the

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