Treat as soon as possible has become the standard of care for all HIV-infected individuals.1

Managing treatment has shifted with the evolution of more efficacious and less toxic antiretroviral therapy (ART) as compared to the first treatments developed in the 1990s.1-3 In the United States, the DHHS recommends ART regardless of viral load or CD4 count. This has been their recommendation since January 2016.1 The World Health Organization recommends ART for all HIV-infected individuals regardless of CD4 count.4 Further, the International Antiviral Society-USA provides guidance that the majority of viremic patients be started on ART regardless of CD4 count.5 Initiation of treatment is also recommended in infected patients with undetectable viral loads but whose CD4 counts are dropping.5 These guidelines establish the treatment of HIV as early as possible as the standard of care.1,4,5 On a case-by-case basis, ART may be deferred because of clinical and/or psychosocial factors, but therapy should be initiated as soon as possible.1

Over the past several years, DHHS recommendations have changed from initiating ART in patients with AIDS-defining illness or in those with a CD4 cell count <350 cells/mm3 to the 2012 recommendation to initiate ART for all HIV-infected patients regardless of CD4 cell count, but with the strength of the recommendation higher for lower CD4 cell counts.1,6

Today and since early 2016, the recommendation is to treat regardless of CD4 cell count1

During this time, the range of available treatment options has broadened to include more single-tablet regimens, more once-daily regimens, and more integrase-inhibitor-based regimens.1,7

Two large international randomized controlled trials, START (Strategic Timing of Antiretroviral Therapy) and TEMPRANO, which evaluated the optimal time to initiate ART and demonstrated a protective effect, are support for the recommendation for the earliest possible treatment initiation.1

See study designs and additional findings for START and TEMPRANO.


The START study was a large multinational randomized controlled clinical trial of 4,685 treatment-naive adults that evaluated the role of immediate ART in asymptomatic HIV-infected patients with CD4 counts >500 cells/mm3.1 The primary clinical endpoint was a composite outcome that included any serious AIDS-related event, whether death from AIDS or any AIDS-defining illnesses, as well as any serious non-AIDS events, including death.1,8 Patients were randomized to an immediate initiation arm or deferred initiation arm until CD4 counts declined to <350 cells/mm3 or until they developed a clinical indication for therapy.1

Selected Results

  • A 57% (95% Cl, 0.30 to 0.62) relative reduction was reported for primary endpoint outcomes with the immediate treatment with ART8
  • Benefits of immediate ART were evident across all participant subgroups (including men and women, older and younger, high and low plasma HIV-1 RNA levels, residents of high-income and low/middle-income countries)1,8
    • Immediate ART also significantly reduced the relative rate of pooled serious and non‐AIDS‐related events by 39% (relative reduction; 95% Cl, 0.38 to 0.97) and serious AIDS-related events by 72% (relative reduction; 95% Cl, 0.15 to 0.50)1,8


The TEMPRANO ANRS 12136 study was a multicenter, randomized controlled trial of more than 2,000 participants conducted in Cote d'Ivoire to assess the benefits of early ART, 6‑month isoniazid preventive therapy (IPT), or both. HIV‑infected participants with CD4 counts of <800 cells/mm3 were randomized to four treatment arms to either immediate or deferred ART, or each of those arms with IPT. The primary composite endpoint was AIDS diseases, non-AIDS malignancies, non-AIDS invasive bacterial diseases and death from any cause.1,9

Selected Results

  • Primary endpoint events: 204 primary endpoint events were recorded in 175 patients (3.8 events per 100 person-years; 95% CI, 3.3 to 4.4), including 68 in patients with a baseline CD4 count of at least 500 cells/mm3 (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0)9
  • Early ART reduced the risk of death or severe HIV‑related illness (components of composite primary endpoint) as compared to deferred initiation of ART by 44% (hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4 count of ≥500 cells/mm3, 0.56; 95% CI, 0.33 to 0.94)9
  • The study team concluded that early ART is clinically beneficial9

Initiating treatment as soon as possible led to1:
~50% reduction in morbidity and mortality for HIV-infected patients who had CD4 counts >500 cells/mm3


Several studies of varying design and patient populations that have been conducted across the world have concluded that the earliest possible initiation of ART—sometimes within 24 hours of diagnosis—can improve and sustain viral suppression and reduce transmission.10-13

By condensing or accelerating the process involved with the initiation of ART, these studies represent a shift in the established treatment paradigm, demonstrating that earlier initiation is not only possible but feasible.10,11


as soon as possible and ideally on the day of first referral

  • 94.9% (37 of 39) of patients began ART within 24 hours10
  • Improved time to virologic suppression for patients initiated same day (1.8 months to viral load <200 copies/mL vs 4.3 months in standard arm, P=0.0001)10
  • Intervention included education, screening, insurance services, and telephone follow-up10

within 24 hours of HIV clinic visit

  • Improvements in uptake of ART and viral suppression with single-visit initiation11
  • 64% of rapid initiation arm (119/187) were virally suppressed at 10 months compared to 51% (96/190) in standard initiation arm (HR 1.06; 95% CI, 0.61–1.84)11
  • Post-initiation loss to care was higher in the rapid arm, pre-initiation loss to care was higher in the standard arm; attrition rates remained similar in both groups11

immediate initiation in acute recent HIV

  • Demonstrated rapid reduction in plasma and semen viral load12
  • Greater declines in plasma cytokines across phases of infection, and faster time to viral load decay for patients in earlier stages of infection
    • The absolute difference in plasma viral load (log viral load change/week) through 24 weeks was 0.07 for the immediate treatment arm vs 0.02 for the deferred arm (P<0.001)12

ART Observational
within 30 days of diagnosis

  • 26% (22/86) initiated ART at first visit13
  • 79% of those who initiated upon clinical intake achieved viral suppression at Week 12 vs 57% of remaining study population (P=0.068)13
  • Shorter time to viral suppression with integrase-inhibitor-based vs protease-inhibitor-based regimens (P=0.022)13


The role of ART in preventing secondary transmission has the potential to positively affect HIV incidence at the population level, and to lower prevalence.1,14 High levels of plasma HIV‐1 RNA are a major risk factor in the transmission of HIV, and effective ART can reduce—by over 90%—viremia and HIV transmission to sexual partners.1,15 Modelling studies indicate that incidence and prevalence of HIV on a community or population level might be lowered by expanded use of ART.14 Reducing the risk of HIV transmission is a secondary goal of ART.1

To learn about a comprehensive prevention approach to HIV acquisition, go to

So, the idea is that with [the patient's] antiretroviral regimen and good adherence, they can maintain viral suppression, therefore reducing their risk of transmission.

—Derrick Butler, MD


on the role of treatment in preventing secondary transmission.

  1. U.S. Department of Health and Human Services. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Available at Accessed November 16, 2017.
  2. Nachega JB, Parienti JJ, Uthman OA, et al. Lower pill burden and once-daily antiretroviral treatment regimens for HIV infection: a meta-analysis of randomized controlled trials. Clin Infect Dis. 2014;58(9):1297-1307.
  3. Halkitis PN, Shrem MT, Zade DD, Wilton L. The physical, emotional and interpersonal impact of HAART: exploring the realities of HIV seropositive individuals on combination therapy. J Health Psychol. 2005;10(3):345-358.
  4. World Health Organization. Consolidated guidelines on HIV prevention, diagnosis, treatment, and care for key populations. Available at Accessed June 27, 2017.
  5. Günthard HF, Saag MS, Benson CA, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2016 recommendations of the International Antiviral Society-USA Panel. JAMA. 2016;316(2):191-210.
  6. U.S. Department of Health and Human Services. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available at Accessed June 27, 2017.
  7. FDA. Antiretroviral drugs used in the treatment of HIV infection. Available at Accessed June 27, 2017.
  8. INSIGHT START Study Group, Lundgren JD, Babiker AG, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373(9):795-807.
  9. TEMPRANO ANRS 12136 Study Group, Danel C, Moh R, et al. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. 2015;373(9):808-822.
  10. Pilcher CD, Ospina-Norvell C, Dasgupta A, et al. The effect of same-day observed initiation of antiretroviral therapy on HIV viral load and treatment outcomes in a US public health setting. J Acquir Immune Defic Syndr. 2017;74(1):44-51.
  11. Rosen S, Maskew M, Fox MP, et al. Initiating antiretroviral therapy for HIV at a patient's first clinic visit: the RapIT randomized controlled trial. PLoS Med. 2016;13(5):e1002015. doi:10.1371/journal.pmed.1002015.
  12. Gilada TI, Javier R, Lama JR, et al. Dynamics of viral load and cytokines when ART is initiated soon after HIV acquisition. Poster 466. Presented at: International Antiviral Society-USA conferences on viruses and opportunistic infections. Seattle, WA. February 13-16, 2017.
  13. Hoenigl M, Chaillon A, Moore DJ, et al. Rapid HIV viral load suppression in those initiating antiretroviral therapy at first visit after HIV diagnosis. Sci Rep. 2016;6:32947. doi:10.1038/srep32947.
  14. Granich RM, Gilks CF, Dye C, De Cock KM, Williams BG. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet. 2009;373(9657):48-57.
  15. Cohen MS, Chen YQ, McCauley M, et al. Antiretroviral therapy for the prevention of HIV-1 transmission. N Engl J Med. 2016;375(9):830-839.