The effectiveness of highly active antiretroviral therapy (HAART) in the real world may differ from its effectiveness in clinical trials. This difference has been attributed to factors such as the motivation of individuals who enter clinical trials and the level of support they receive during the trial.

Several studies have shown that HAART in the real world fails to produce high levels of sustained viral suppression. For example, a review of protease inhibitor-naive patients in one clinic found that only 42% had undetectable viral load after three months of treatment (Lucas 1999). Another clinic review found 47% of 310 people who went on protease inhibitor therapy between June 1995 and December 1997 had viral loads below 400 copies/ml after a year of follow-up (Valdez 1999).

However, the earlier poor results have been attributed to prior nucleoside reverse transcriptase inhibitor (NRTI) therapy amongst cohort participants. Certainly prior NRTI therapy has been associated with greater risk of viral rebound, even after two to three years of viral suppression (Phillips 2002).

Other community cohort studies have reported more encouraging results. A EuroSIDA study of 1470 people from 17 European countries found that 80% achieved viral load below 500 copies/ml with 24% rebounding within six months (Paredes 2000). Participants commenced a protease inhibitor or non-nucleoside reverse transcriptase inhibitor (NNRTI) for the first time, in combination with NRTIs. Factors associated with sustained viral suppression in this study were:

• Lower baseline viral load.

• Higher baseline CD4 count.

• Initiation of three of more new drugs.

• No previous antiretroviral treatment.

• Use of a protease inhibitor other than hard gel saquinavir (Invirase).

A second, community cohort study called the Swiss HIV Cohort Study found that 20% of participants on HAART experienced virological failure, while 63% achieved a viral load below 400 copies/ml. At 18 months, the rate of disease progression was 4% among those on HAART, demonstrating the effectiveness of HAART in real world settings (Erb 2000).

A recent study from the United States has also shown that the response to HAART improved between 1996 and 2002, with more patients achieving undetectable viral loads and increases in CD4 cell count as time went on. By 2002, 80% of patients on HAART for a year or more had viral loads below 400 copies/ml and the mean CD4 cell count increase was 142 cells/mm³. The study also found that use of an NNRTI or a boosted protease inhibitor was associated with better outcome than use of an unboosted protease inhibitor. The investigators believe that the increased effectiveness may be due to improvements both in therapy and in the expertise in using the available drugs (Moore 2005).

Factors that have been associated with poor response to treatment include:

• Poor adherence to treatments.

• Non-white ethnicity.

• Age under 40 years.

• Injecting drug use.

• Lower baseline CD4 cell count.

• Higher baseline viral load.

• Slower initial response to treatment.

• Higher lowest-ever viral load.

• Lower protease inhibitor levels in the blood.

• Poor attendance at clinical appointments.

• Low body weight.

• A history of Pneumocystis pneumonia (PCP) or PCP prophylaxis.

• Use of prescription narcotics such as benzodiazepines.

• Heroin or cocaine use.

• Heavy alcohol consumption.

• Female gender.

References

Clough LA et al. Factors that predict incomplete virological response to protease inhibitor-based antiretroviral therapy. Clin Infect Dis 29: 75-81, 1999.

Egger M et al. Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet 360: 119-129, 2002.

Erb P et al. Effect of antiretroviral therapy on viral load, CD4 count, and progression to acquired immunodeficiency syndrome in a community human immunodeficiency virus-infected cohort. Arch Intern Med 160: 1134-1140, 2000.

Knobel H et al. Virologic outcome and predictors of virologic failure of highly active antiretroviral therapy containing protease inhibitors. AIDS Patient Care STDS 15: 193-199, 2002.

Lucas GM et al. Highly active antiretroviral therapy in a large urban clinic: risk factors for virologic failure and adverse drug reactions. Ann Intern Med 131: 81-87, 1999.

Lucas GM et al. Longitudinal assessment of the effects of drug and alcohol abuse on HIV-1 treatment outcomes in an urban clinic. AIDS 16: 767-774, 2002.

Moore RD et al. An improvement in virologic response to highly active antiretroviral therapy in clinical practice from 1996 through 2002. J Acquir Immune Defic Syndr 39): 195-198, 2005.

Palella FJ et al. Durability and predictors of success of highly active antiretroviral therapy for ambulatory HIV-infected patients. AIDS 16: 1617-1626, 2002.

Paredes R et al. Predictors of virological success and ensuing failure in HIV-positive patients starting highly active antiretroviral therapy in Europe. Arch Intern Med 160: 1123-1132, 2000.

Phillips AN et al. Human immunodeficiency virus rebound after suppression to <400 copies/ml during initial highly active antiretroviral therapy regimens, according to prior nucleoside experience and duration of suppression. J Infect Dis 186: 1086-1091, 2002.

Powderly WG et al. Predictors of optimal virological response to potent antiretroviral therapy. AIDS 13: 1873-1880, 1999.

Valdez H et al. Human immunodeficiency virus 1 protease inhibitors in clinical practice. Arch Intern Med 159: 1771-1776, 1999.