Spanish researchers have found further evidence to support the initiation of antiretroviral therapy before a patient’s CD4 cell count falls below 350 cells/mm3. A study published in the February 1st edition of the Journal of Acquired Immune Deficiency Syndromes showed that patients who started anti-HIV therapy with CD4 cell counts between 200 – 350 cells/mm3 were significantly more likely to experience the progression of their HIV disease than patients who initiated therapy with a CD4 cell count above this level.
HIV treatment guidelines in the US and Europe already recommend that antiretroviral therapy should be started before an individual’s CD4 cell count falls below 350 cells/mm3 and revised UK guidelines (currently undergoing review prior to publication) make a similar recommendation.
The Spanish investigators also found that patients who had high viral loads when they started anti-HIV therapy had an increased risk of disease progression as did patients with a history of injecting drug use and those who were coinfected with hepatitis C virus.
Rates of illness and death have fallen dramatically in HIV-positive patients since the introduction of effective antiretroviral therapy in the mid 1990s. But the currently available anti-HIV drugs are not able to cure HIV and have several limitations including side-effects, a need for high levels of adherence, and drug resistance.
There are also uncertainties about the best way to use anti-HIV treatment. Until recently, HIV treatment guidelines recommended that anti-HIV therapy should be delayed until a patient’s CD4 cell count had fallen to 200 cells/mm3. But evidence emerged showing that starting treatment at higher CD4 cell counts lead to better long-term improvements in the immune system, and that patients with lower CD4 cell counts have a higher risk of serious illnesses including some cancers as well as heart, kidney and liver disease.
To gain a better understanding of the factors associated with HIV disease progression and the best time to start antiretroviral therapy, investigators from the Spanish PISCIS cohort performed a study involving 2035 treatment-naïve, AIDS-free patients who started antiretroviral therapy between 1998 and 2004.
At the time when anti-HIV treatment was initiated, 760 patients had a CD4 cell count below 200 cells/mm3, 650 had counts between 200 – 350 cells/mm3, and 625 had a CD4 cell count above 350 cells/mm3. Median age was 36 years and 75% of the patients were men.
Median follow-up was a little under three years, and in this period 148 (7%) patients experienced progression to a new AIDS-defining illness or death.
Factors associated with disease progression were a CD4 cell count below 200 cells/mm3 at baseline (p
The investigators then performed another set of analyses, this time taking into account “lead time” – the length of time a patient had HIV. This showed that patients who started anti-HIV therapy with a CD4 cell count between 200 – 350 cells/mm3 had, compared to patients who started treatment with a CD4 cell count above 350 cells/mm3, an 85% increase in their risk of progressing to AIDS or dying (HR = 1.85; 95% CI, 1.03 – 3.33).
“These results provide valuable information for clinical decisions about when to start [antiretroviral therapy], particularly now that we have better antiretroviral drugs and more comfortable regimens”, conclude the investigators.
Jaen A et al. Determinants of HIV progression and assessment of the optimal time to initiate highly active antiretroviral therapy: PISCIS cohort (Spain). J Acquir Immune Defic Syndr 47: 212 – 220, 2008.