Effectiveness

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