More data is accumulating that initiation of combination antiretroviral therapy may have a greater impact on preservation of immune function when used earlier in the course of disease, and CDC guidelines for the use of combination therapy following high risk exposure is derived from the knowledge that productive infection may be prevented when the amount of virus is low and there is little provirus (viral RNA converted to DNA and inserted into the host genome). Berrey and colleagues presented data comparing the virologic and clinical course of 70 patients with primary HIV infection who were evaluated within 90 days of symptom onset. As this study included individuals evaluated between 1993 and 1997, only the last 20 patients evaluated received combination therapy, consistent with the bias towards treatment in this setting during the last two years.

Twenty patients were immediately treated with AZT, 3TC, indinavir, while the first 50 received no therapy. Comparing the two groups at enrollment, both exhibited similar viral load and immune parameters (145,864 copies/ml; mean 697 CD4 cells/dl in treated vs. 119,769 copies/ml; mean 624 CD4 cells/dl in untreated).

Tolerability to the combination therapy appeared as follows:

• 9/20 required change from AZT to D4T due to anemia or nausea and vomiting
• 2/20 had grade 3 or 4 increase in bilirubin or increase transaminase (pt had Hepatitis A)
• 4/8 had triglycerides > 200 at 6-18 months following therapy initiation
• 16/20 remained on treatment at 12 months
• 15/20 on treatment at 18 months

All treated patients achieved undetectable levels of HIV RNA (<500 copies) by week 12, and all patients remaining on therapy by week 24 were undetectable at <20 copies/ml. During the 18 months of follow up, the treated group gained an average of 8.8 CD4 cells per month while the untreated group lost an average of 13.8 CD4 cells, month (p=0.0018). Furthermore none of the treated patients developed any major or minor complications of HIV, while in the untreated group 6 developed oral candida, 6 demonstrated oral hairy leukoplakia, 3 experienced peripheral neuropathy and one had esophageal candidiasis. Although this study demonstrates clinical benefit from early initiation of combination therapy, it will require ongoing follow up to determine whether clinical benefits will be sustained.