Thirty-five years have now passed since the beginning of the AIDS epidemic, and it’s been two decades since the introduction of effective combination antiretroviral (ARV) treatment. To mark this double anniversary, here’s a comprehensive timeline of the milestones in drug development and access to therapies that have dramatically transformed the global pandemic.

1981

  • The AIDS epidemic officially begins, as the Centers for Disease Control and Prevention (CDC), in June and July, issues the first reports of fatal cases of Pneumocystis carinii pneumonia (PCP) and Kaposi’s sarcoma (KS) among gay men.
  • The New York Times is the first major news source to report on the epidemic, in a short article published on July 3, 1981.

1983

  • HIV, which was initially called HTLV-III/LAV, is identified as the cause of AIDS.

1985

  • The first HIV test is approved.
  • A total 16,000 U.S. residents have been diagnosed with AIDS; half of them have died.
  • Clinical trials begin with nucleoside reverse transcriptase inhibitors (NRTIs, or nukes); Retrovir (zidovudine, or AZT) is the first investigated.

1986

  • A Phase II trial of AZT is stopped early because those on AZT have a higher survival rate than those taking the placebo.

1987

  • Retrovir (zidovudine, or AZT), the first NRTI, is approved by the U.S. Food and Drug Administration (FDA).
  • Research shows that those taking AZT have a greater survival rate at 24 weeks of treatment. But by week 48 on the drug, these survival benefits vanish.
  • Congress passes $30 million in emergency funding for AZT, setting the stage for what would become the AIDS Drug Assistance Program (ADAP), written into law in the 1990 Ryan White CARE Act.
  • In reaction to the high price of AZT, activists found the influential group ACT UP. They succeed in pressuring Burroughs Welcome to lower the cost of the antiretroviral (ARV).

1988

  • ACT UP stages a major protest at the FDA headquarters, lambasting the slow pace of HIV treatment developments.
  • More than 80,000 U.S. residents have been diagnosed with AIDS; more than 45,000 of them have died.

1989

  • Scientists first describe how HIV develops resistance to AZT.
  • Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID) backs the parallel track clinical trials process, which opens the door for greater access to investigational HIV treatments among people with HIV who otherwise would not qualify to participate in clinical trials.

1990

  • Congress passes the Ryan White CARE Act, which becomes a major source of funding for HIV care and treatment.

1990

  • Videx (didanosine, or ddI) is approved.
  • More than 200,000 U.S. residents have been diagnosed with AIDS; 131,000 have died.

1992

  • HIV becomes the number one cause of death for men in the United States ages 25 to 44.
  • Hivid (zalcitabine, or ddC) is approved.

1993

  • Research from the Concorde trial, presented at the International AIDS Conference in Berlin, shows that NRTI monotherapy (taking only one ARV at a time) is associated only with short-term benefits. There are no long-term survival benefits.
  • The first Phase I and Phase II clinical trial results of protease inhibitors (PIs) are presented at the Berlin conference.

1994

  • Zerit (stavudine, or d4T) is approved.
  • AIDS becomes the number one cause of death for U.S. residents ages 25 to 44.
  • Researchers establish that AZT reduces mother-to-child transmission of HIV. The U.S. Public Health Service recommends its use for this purpose.
  • About 435,000 U.S. residents have been diagnosed with AIDS; 267,000 have died.

1995

  • Epivir (lamivudine) is approved.
  • Invirase (saquinavir), the first protease inhibitor, is approved.
  • Research shows that treating HIV with two NRTIs at once is superior to monotherapy.
  • Scientists determine that viral load predicts HIV disease progression.
  • The latent viral reservoir is discovered. Researchers will come to understand that its existence prevents ARV treatment from curing HIV.

1996

  • 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 (HAART).
  • Researcher David Ho, MD, who was instrumental in the development of HAART, advocates a “hit early, hit hard” HIV treatment ethos. He also suggests (incorrectly, it would turn out) that a few years of combination ARV treatment may cure the virus. He is named Time magazine’s Man of the Year.
  • The first viral load test is approved, giving clinicians a marker for determining the success of ARV treatment. An undetectable viral load is the goal.
  • Viramune (nevirapine), the first non-nucleoside reverse transcriptase inhibitor (NNRTI), is approved.
  • Crixivan (indinavir) is approved.
  • Norvir (ritonavir), a protease inhibitor that would become a booster of other ARVs, is approved.
  • The number of new AIDS cases in the United States declines for the first time.
  • AIDS is no longer the leading cause of death for Americans 25 to 44 but still is for blacks in this age bracket.

1997

  • AIDS-related deaths have dropped 47 percent in one year.
  • Combivir (zidovudine/lamivudine), the first NRTI combination tablet, is approved.
  • Rescriptor (delavirdine) is approved.
  • Viracept (nelfinavir) is approved.
  • Drug resistance to protease inhibitors becomes a major concern.

1998

  • Ziagen (abacavir) is approved.
  • Sustiva (efavirenz) is approved.
  • The S. Department of Health and Human Services issues the first federal HIV treatment guidelines, recommending treatment for those with fewer than 500 CD4s.

2000

  • Trizivir (abacavir/zidovudine/lamivudine) is approved.
  • Videx EC is approved.
  • Kaletra (lopinavir/ritonavir), the first boosted protease inhibitor in a single tablet, is approved.
  • ARV resistance testing becomes a standard part of HIV care, helping guide decisions about the best meds individuals should take.
  • AIDS becomes the number one cause of death in Africa.
  • Researchers first identify the metabolic toxicities associated with ARVs.
  • Closely tied with these toxicities is lipodystrophy, or the abnormal body fat changes, linked with early HIV medications. Eventually, research will establish the culprits as Retrovir (AZT, or zidovudine), which is also in Combivir (zidovudine/lamivudine) and Trizivir (abacavir/zidovudine/lamivudine); Zerit (d4T, or stavudine); and Videx (ddI, or didanosine).
  • UNAIDS negotiates with five pharmaceutical companies to lower the prices of ARVs for poorer nations.

2001

  • Viread (tenofovir disoproxil fumarate, or TDF), which causes bone and kidney toxicities, is approved and goes on to become the most widely prescribed ARV.
  • TDF’s manufacturer, publishes research on a new formulation of tenofovir: tenofovir alafenamide, or TAF.
  • Generic manufacturers begin providing bulk, low-cost access to ARVs in the developing world. Consequently, pharmaceutical companies agree to further reduce the prices of their HIV drugs.
  • U.N. General Secretary Kofi Annan proposes the creation of The Global Fund to Fight AIDS, Tuberculosis and Malaria.
  • Doing an about-face, U.S. treatment guidelines switch to recommending starting ARVs when CD4s have dropped to 200 or below.

2002

  • The Global Fund is launched with a $600 million first round of grants.

2003

  • Emtriva (emtricitabine) is approved.
  • Lexiva (fosamprenavir) is approved.
  • Reyataz (atazanavir) is approved.
  • The first entry inhibitor, the injectable Fuzeon (enfuvirtide), is approved.
  • President George 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 World Health Organization (WHO) announces the 3x5 Initiative, aiming to get 3 million people on HIV treatment by 2005.
  • The Clinton Foundation secures price reductions for ARVs from generic manufacturers for use in developing nations.

2004

  • Gilead halts research of TAF but still applies for patents on the drug.
  • Epzicom (abacavir/lamivudine) is approved.
  • Truvada (tenofovir disoproxil fumarate, or TDF/emtricitabine) is approved.
  • PEPFAR begins its first funding rounds.

2005

  • Aptivus (tipranavir) is approved.

2006

  • Atripla (efavirenz/tenofovir/emtricitabine), the first once-daily HIV single-tablet regimen, is approved.
  • Prezista (darunavir) 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 and non-AIDS-defining conditions such as heart disease.

2007

  • The first integrase inhibitor, Isentress (raltegravir), is approved.
  • The first oral entry inhibitor, Selzentry (maraviroc), is approved.
  • The goal of getting 3 million people worldwide on ARVs is reached, two years late.

2008

  • Intelence (etravirine) is approved.
  • Congress reauthorizes PEPFAR for five years for up to $48 billion.
  • Researchers establish a proof of concept that people who have failed multiple HIV regimens can achieve durable suppression of the virus by using combinations of at least two new fully active ARVs.
  • As HIV treatments improve, U.S. treatment guidelines up the CD4 threshold for starting ARVs to 350.

2009

  • “The Berlin Patient”—a HIV-positive man named Timothy Ray Brown who underwent two bone marrow transplants involving HIV-resistant stem cells, in 2007 and 2008, for the treatment of leukemia—is classified as cured of the virus.

2010

  • As San Francisco recommends HIV treatment regardless of CD4 count, U.S. guidelines advise starting ARVs when CD4s drop to 500, while WHO’s threshold is 350 CD4s.
  • Obama signs the Affordable Care Act (ACA, or Obamacare). The state Medicaid expansion element in particular, as well as the elimination of exclusions for preexisting conditions, promises to help many people with HIV obtain coverage for treatment.
  • U.S. treatment guidelines shift to recommending treatment with 500 or fewer CD4s.
  • WHO changes its treatment guidelines, recommending starting ARVs with 350 CD4s or less.
  • Gilead tells investors that it will begin researching TAF, which the company characterizes as a new molecule.
  • The global iPrEx study proves Truvada (tenofovir/emtricitabine) as pre-exposure prophylaxis’ (PrEP) efficacy among men who have sex with men (MSM) and transgender women.

2011

  • The HPTN 052 study finds that starting ARVs reduces the risk of transmitting HIV through heterosexual sex by 96 percent, launching the treatment-as-prevention (TasP) era.[9]
  • The TDF2 and Partners PrEP studies prove PrEP’s efficacy in heterosexuals.
  • Complera (rilpivirine/tenofovir/emtricitabine) is approved.
  • Edurant (rilpivirine) is approved.
  • Seven million people worldwide are taking ARVs.
  • UNAIDS sets a target of getting 15 million on treatment by 2015.

2012

  • The Supreme Court affirms the ACA as the law of the land but permits state governments to opt out of expanding their Medicaid programs. By and large, Republican-dominated states refrain from such expansions, which in particular compromises access to HIV care in the hard-hit South.
  • U.S. guidelines recommend treatment for all people living with HIV, regardless of their CD4 count.
  • Stribild (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate) is approved.
  • Truvada is approved in the United States for use as PrEP.

2013

  • Tivicay (dolutegravir) is approved.
  • UNAIDS reports that global AIDS-related deaths have fallen 30 percent since peaking in 2005.
  • According to UNAIDS, an estimated 35 million people are living with HIV. In 2012, 2.3 million were newly infected with the virus while 1.6 million died of AIDS-related causes, down from a high of 2.3 million in 2005. The HIV infection rate has dropped by more than half in 26 countries between 2001 and 2012. A total of 9.7 million people had access to ARVs at the end of 2012.
  • An estimated 1.2 million Americans are HIV positive (recent research suggests this is an overestimate).
  • Secretary of State John Kerry says more than 1 million infants have been born without HIV since 2003.[10]
  • WHO guidelines recommend treatment when CD4s drop below 500, instead of 350.

2014

  • Americans have access to private health plans through the ACA for the first time, and state Medicaid expansions begin in states that have approved them. Preexisting condition exclusions and annual limits on health coverage are now forbidden.
  • Interim results from the ongoing PARTNER study find that there have been no transmissions in gay and 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 zero.
  • Triumeq (dolutegravir/abacavir/lamivudine) is approved.
  • Tybost (cobicistat) is approved.
  • Vitekta (elvitegravir) is approved.
  • UNAIDS calls for the rapid ratcheting up of HIV prevention and treatment programs to prevent 28 million new transmissions and end the epidemic as a public health threat by 2030.
  • UNAIDS launches the 90-90-90 targets for 2020, seeking to get 90 percent of the world’s HIV population diagnosed, 90 percent of the diagnosed population on treatment and 90 percent of the treated population to a fully suppressed viral load, for an overall viral suppression rate of 73 percent.
  • The global rollout of ARV treatment has averted an estimated 7.8 million deaths since 2000.

2015

  • 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. Gilead goes on to gain approval for TAF-inclusive versions of all of its TDF-inclusive tablets, except for Atripla, which is no longer a recommended first-line therapy.
  • Evotaz (atazanavir/cobicistat) is approved.
  • Prezcobix (darunavir/cobicistat) is approved.
  • UNAIDS says the goal of getting 15 million people on HIV treatment has been reached six months ahead of schedule.

2016

  • Odefsey (emtricitabine/rilpivirine/TAF) is approved.
  • Descovy (emtricitabine/TAF) is approved.
  • UNAIDS reports that 17 million people are on HIV treatment. AIDS Healthcare Foundation questions whether this number is inflated.
  • The CDC reports that annual HIV diagnosis rates have dropped 19 percent over the past decade.
  • Gilead Sciences reports that approximately 50,000 U.S. residents, mostly white males 25 and older, have filled at least one PrEP prescription. Quarterly rates of new PrEP prescriptions soar over 500 percent between 2012 and 2015. The demographic trends of Truvada’s use as prevention question the short-term extent of its impact, considering the vastly disproportionate HIV rates among young black MSM in particular.