Background: The study author, while still a medical student, observed microscopic evidence of chronic inflammation in joint tissue of patients suffering with osteoarthritis and hypothesized that osteoarthritis was caused by an infectious process. After graduating from medical school and entering into private practice, the study author had several patients who informed him that when they were on tetracycline therapy, for reasons other than arthritis, their arthritis symptoms diminished to some extent. After reporting improvement of arthritic symptoms with tetracycline, one of these patients subsequently received metronidazole and while taking both tetracycline and metronidazole reported that his arthritic symptoms improved to an even greater extent, as his joint pain further diminished but did not resolve. Subsequent treatment of osteoarthritis in other patients included the combination of tetracycline, metronidazole, other antibiotics and some natural products but only when L-lysine was added to the tetracycline and metronidazole combination therapy did the author observe yet further improvement in arthritic pain. Since L-lysine was reported to inhibit the growth of herpes simplex virus, the author and another colleague concluded that acyclovir might be a beneficial addition to the tetracycline, metronidazole, L-lysine combination. This four-component combination treatment resulted in total resolution or a marked diminution of osteoarthritis joint pain, joint tenderness and joint stiffness in most patients treated. It was further determined that L-lysine could be eliminated; that acyclovir could be replaced with valicyclovir; and that tetracycline could be replaced with minocycline or doxycycline.
 Preliminary studies of patients diagnosed with osteoarthritis and treated with tetracycline alone or the combination of tetracycline and metronidazole demonstrated improvement in their osteoarthritic symptoms. However the triple combination of doxycycline (broad spectrum antibiotic), metronidazole (antiprotozoal and antibacterial imidazole) and acyclovir (antiviral purine nucleoside) administered orally twice daily for eight weeks showed marked success in a group of patients suffering with osteoarthritis by substantially eliminating their joint pain, joint tenderness and joint stiffness while overcoming their fatigue and increasing their energy level. The data in this report substantiate that this triple combination is a disease modifying therapy that eliminates or markedly diminishes the symptomatology of osteoarthritis and further supports the hypothesis that osteoarthritis is an infectious disease. Objective: To evaluate the effect of the triple combination therapy of doxycycline, metronidazole, and acyclovir on the joint pain, joint stiffness and functionality in patients suffering with osteoarthritis. Design: Non-blinded study of treatment of patients suffering with osteoarthritis Setting: Primary care internal medicine practice in Alameda County, California. Sample: Six adult individuals suffering with osteoarthritis. Patients: Six patients, ages 53 through 82 years. Patient 1 was treated for 28 days and Patients 2 through 6 were treated for 56 days. Method: After obtaining informed consent, six patients suffering with osteoarthritis were prescribed a 56 day course of treatment with the triple combination of doxycycline, metronidazole, and acyclovir for treatment of their osteoarthritis. Utilizing the WOMAC index for assessment of the effectiveness of treatment of osteoarthritis, pre-treatment pain, stiffness and functional limitation, were compared to post-treatment pain, stiffness and functional limitations. Results: Three patients demonstrated total resolution of pain and stiffness and greater than 95% improvement in functional limitations. One of the remaining three patients demonstrated a 70% improvement in pain, total resolution of stiffness, and an 85% improvement in functional limitations; another one of the three remaining patients demonstrated an 86% improvement in pain, total resolution of stiffness, and a 79% improvement in functional limitations; while the last of the three remaining patients demonstrated at least an 85% improvement in pain, 67% improvement in stiffness, and a 63% improvement in functional limitations.
 Limitations: No randomization. No placebo. No control group. Small sample size. Conclusion: The results of treatment of these patients suffering the osteoarthritis support the hypothesis that osteoarthritis is an infectious disease. These results further suggest that osteoarthritis is, at a minimum, modifiable with the triple combination therapy of doxycycline, metronidazole, and acyclovir and is even curative of with this breakthrough treatment in many cases. The medical treatment reported in this article represents the first truly Disease Modifying medication therapy developed for osteoarthritis. 
 Keywords: WOMAC index