CD4-guided treatment interruption reduces time on therapy by two-thirds

Keith Alcorn
Estimated reading time 3 minutes
This article is more than 22 years old.

A Thai study of structured treatment interruption has found that using the CD4 cell count to guide the resumption of therapy is just as effective as a one week on, one week off approach in terms of preventing clinical illness. Both approaches proved just as effective as continuous treatment in preventing clinical illness.

The study was reported today at the Tenth Conference on Retroviruses and Opportunistic Infections, in Boston, alongside a Spanish study which found that 43% of patients randomised to CD4-guided treatment interruption were able to stay off treatment for at least 48 weeks.

Thai study

Seventy four patients who had been on treatment for four years and who had viral load below 50 copies/ml and CD4 cell counts above 350 were randomised either to continuous therapy, stopping therapy until their CD4 cell count fell below 350 or fell 30% from baseline, or to one week on, one week off therapy

After 48 weeks follow-up the following significant differences emerged:

Glossary

treatment interruption

Taking a planned break from HIV treatment, sometimes known as a ‘drugs holiday’. As this has been shown to lead to worse outcomes, treatment interruptions are not recommended. 

nadir

Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

seroconversion

The transition period from infection with HIV to the detectable presence of HIV antibodies in the blood. When seroconversion occurs (usually within a few weeks of infection), the result of an HIV antibody test changes from HIV negative to HIV positive. Seroconversion may be accompanied with flu-like symptoms.

 

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

  • A median CD4 decline of 178 cells/mm3 in the CD4-guided group, compared to minimal change in the other arms. However, this did not translate into a higher rate of clinical events in this group. No AIDS-defining illnesses or deaths occurred in any arm. There was no significant difference between the groups in the number of patients with CD4 cell count below 350 at week 48.

  • The CD4 guided group took HAART for just one third of the time of the continuous therapy group (33% of the time on treatment), whilst the one week on, one week off group took HAART for 59% of the time of the continuous therapy group.

  • The one week on, one week off group were more likely to have detectable viral load (46% > 500 copies/ml); seven patients in this arm were classified as viral failures (viremia remained detectable after resumption of HAART), compared with none in the other arms.

Spanish study

The Spanish study randomised 122 patients on HAART with CD4 counts above 500 cells/mm3 for at least six months, nadir CD4 count above 100 cells/mm3 and viral load below 80 copies/ml, to continuous therapy or to discontinue treatment until they had experienced a CD4 cell decline below 350 cells/mm3, or a viral load increase above 100,000 copies/ml or an opportunistic infection. Any patients who resumed therapy would be eligible to stop again once their CD4 cell count rose above 500 cells/mm3 and viral load had been suppressed below 80 copies/ml.

At baseline the median CD4 cell count was 800 in the continuous treatment group and 850 cells/mm3 in the treatment interruption group. Fifty seven per cent subsequently resumed HAART, within a median of 8 weeks, overwhelming due to a viral load increase above 100, 000 copies/ml (97%).

Amongst those who remained off treatment for at least 48 weeks the median CD4 cell decline was 335 cells/mm3 (an average decline of 33 cells per month). None developed opportunistic infections. CD4 cell counts remained stable in the continuous treatment group, although two patients experienced viral rebound.

A higher nadir CD4 cell count and and a higher CD4 count prior to treatment interruption were associated with greater duration of treatment interruption, but reporting the study, Lydia Ruiz of the IrisCaixa Foundation, Barcelona said: "We don't know the optimum nadir for pursuing this strategy yet".

Ten per cent of those who interrupted treatment developed an acute retroviral syndrome, and 41% of all those who stopped reported at least one symptom characteristic of seroconversion illness, such as fever, rash or headache.

Further information on this website

Structured treatment interruption – overview of key studies and issues

Intermittent therapy – studies of approaches to sparing treatment, using CD4-guided treatment interruptions

References

Ananworich J et al. HIV-NAT 001.4: a prospective randomised trial of structured treatment interruption in patients with chronic HIV infection. Tenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 64, 2003.

Ruiz L et al. A multi-center, randomised, controlled clinical trial of continuous vs intermittent HAART guided by CD4+ T-cell counts and plasma HIV-1 RNA levels. Tenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 65, 2003.

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