Tenofovir (Viread) is an effective antiviral agent that can reduce HIV viral load. As a first-line therapy in combination with other antiretrovirals (ARVs), tenofovir is equivalent to most nucleoside reverse transcriptase inhibitors (NRTIs). Despite the absence of long-term safety data, tenofovir is an attractive first-line option for HIV-positive patients.

In Study 903, over 600 people who had not previously used ART were randomised to receive tenofovir or d4T (stavudine; Zerit), plus 3TC (lamivudine, Epivir) and efavirenz (Sustiva). Intent-to-treat analysis showed that both arms had similar virological outcomes, with 76% of people in the tenofovir arm achieving viral load below 50 copies/ml as compared to 80% in the d4T arm. Equivalence was also demonstrated at weeks 96 and 144. At week 144, the mean increase in CD4 cell count was 263 cells/mm3 in the tenofovir arm and 283 cells/mm3 in the d4T arm.1

Results from a study of treatment combinations containing tenofovir in treatment-experienced patients are also encouraging. After nine months’ follow-up, tenofovir was well tolerated with modest virological and immunological outcomes.2 This was supported by the findings of a cohort study based in two large United States clinics, showing efficacy of tenofovir-based treatment regimens in treatment-naive and highly experienced patients.3

Several intensification studies have shown that adding tenofovir to an existing regimen can provide benefit in treatment-experienced people with detectable viral load. In Study 907, 550 treatment-experienced people with detectable viral load were randomised to add tenofovir or placebo to their treatment regimen.4

In the tenofovir arm, 22% reached viral load below 50 copies/ml after 24 weeks, compared to 1% in the placebo group. After one year, the average viral load reduction was 0.57 log10 in the tenofovir arm. A similar study found that the addition of tenofovir to a failing regimen produced an average reduction in viral load of 0.62 log10. 5 6

Factors shown to be associated with an increased chance of virological failure in treatment-experienced patients taking combinations including tenofovir include advanced HIV disease, having a baseline viral load above 100,000 copies/ml, a CD4 cell count below 200 cells/mm3 and resistance to protease inhibitors, especially ritonavir-boosted lopinavir (Kaletra).7

Tenofovir has also been investigated as a treatment to prevent HIV infection in people who are likely to be exposed to the virus, as pre-exposure prophylaxis (PrEP). While animal studies have shown promise, human studies have been difficult to carry out.8 9

Tenofovir is also effective against hepatitis B. Use of tenofovir in HIV and hepatitis B co-infected people showed a significant drop in hepatitis B viral load and, in some cases, clearance of hepatitis B virus.10 11

In also seems to be effective in people with hepatitis B virus that is resistant to 3TC.12 13 An analysis of a subset of patients enrolled in Study 903 showed that combination treatment with tenofovir and 3TC is more effective in treating hepatitis B virus than is 3TC alone.14 This was confirmed in another long-term study.15

However, in July 2004, the United States Food and Drug Administration added a warning to tenofovir’s product label, stating that the drug’s safety for the treatment of HIV and hepatitis B co-infection has not yet been demonstrated. In contrast, the current guidelines of the British HIV Association continue to recommend tenofovir as a potential first-line treatment for co-infected patients, alongside 3TC.

A small observational study has suggested that tenofovir is eliminated from the body very slowly. Although it requires confirmation in a larger study, the investigators estimated that it takes around 7.5 days for half of the drug to be eliminated. This indicates a need for care when discontinuing the drug to avoid the risk of resistance while tenofovir levels fall. However, it may be reassuring for patients who have missed occasional doses of the drug, provided it is paired with other drugs with similarly slow rates of elimination, such as 3TC, FTC, and efavirenz.16

Tenofovir reaches higher levels in the semen than in the blood, suggesting that it may have anti-HIV activity in the male genital tract.17


  1. Gallant JE et al. Efficacy and safety of tenofovir DF vs. stavudine in combination therapy in antiretroviral-naive patients. A 3-year randomized trial. JAMA 292: 191-201, 2004
  2. Gallais H et al. The VireadTM expanded access program (EAP) in Europe / Australia: summary of the safety and efficacy of tenofovir disoproxil fumarate (TDF) in antiretroviral treatment (ART) experienced patients. 15th International AIDS Conference, Bangkok, abstract TuPeB4552, 2004
  3. Scott JD et al. Retrospective review of the use of tenofovir DF in 2 clinical practices. 15th International AIDS Conference, Bangkok, abstract TuPeB4633, 2004
  4. Squires K et al. Tenofovir disoproxil fumarate in nucleoside-resistant HIV-1 infection: a randomized trial. Ann Intern Med 139: 313-320, 2003
  5. Schooley R et al. Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study. AIDS 16: 1257-1263, 2002
  6. Margot NA et al. Genotypic and phenotypic analyses of HIV-1 in antiretroviral-experienced patients treated with tenofovir DF. AIDS 16: 1227-1235, 2002
  7. Nguyen Van JC et al. Predictive factors of virological response to a combination including tenofovir (TDF) in a cohort of highly active antiretroviral therapy-failed HIV-1 patients. 15th International AIDS Conference, Bangkok, abstract WePeB5724, 2004
  8. Tsai CC et al. Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl)adenine. Science 270: 1197-1199, 1995
  9. Van Rompay KK et al. Two low doses of tenofovir protect newborn macaques against oral simian immunodeficiency virus infection. J Infect Dis 184: 429-438, 2001
  10. Ristig MB et al. Tenofovir disoproxil fumarate therapy for chronic hepatitis B in human immunodeficiency virus / hepatitis B virus coinfected individuals for whom interferon-alpha and lamivudine therapy have failed. J Infect Dis 186: 1844-1847, 2002
  11. Stephan C et al. Impact of tenofovir-containing antiretroviral therapy on chronic hepatitis B in a cohort co-infected with human immunodeficiency virus. J Antimicrob Chemother 56: 1087-1093, 2005
  12. Neff GW et al. Tenofovir therapy for lamivudine resistance following liver transplantation. Ann Pharmacother 38: 1999-2004, 2004
  13. Benhamou Y et al. Anti-hepatitis B virus efficacy of tenofovir disoproxil fumarate in HIV-infected patients. Hepatology 43: 548-555, 2006
  14. Dore G et al. Anti-hepatitis B virus (HBV) activity in HBV / HIV co-infected patients treated with tenofovir DF (TDF) and lamivudine (LAM) versus LAM alone: 144-week follow-up. 15th International AIDS Conference, Bangkok, abstract MoPeB3308, 2004
  15. Bani-Sadr F et al. Ninety-six-week efficacy of combination therapy with lamivudine and tenofovir in patients coinfected with HIV-1 and wild-type hepatitis B virus. Clin Infect Dis 39: 1062-1064, 2004
  16. Pruvost A et al. Measurement of intracellular didanosine and tenofovir phosphorylated metabolites and possible interaction of the two drugs in human immunodeficiency virus-infected patients. Antimicrobial Agents Chemother 49: 1907-1914, 2005
  17. Ghosen J et al. Penetration of enfuvirtide, tenofovir, efavirenz and protease inhibitors in the genital tract of HIV-1-infected men. AIDS 18: 1958-1961, 2004
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.