The Factors Associated With Clinical Symptoms And Death Of HIV Infections Treated By Highly Active Antiretroviral Therapy

BackgroundAIDS epidemic has experienced three periods, introduction period (1985~1988), transmission period (1989~1994) and increase period (1995 to this day). From 1999, infection cases reported increased 30% every year. HIV has influenced individuals, families and society. In China while the National Free ART Program full began in 2003, it has become one of routine works and responsibility of all levels of Government. Emerging resistance posed a growing threat to the ongoing success and durability of HAART. The developed country has developed many researches on the epidemic and influence of HIV drug resistance. In China because the National Free ART Program full began late, economy and technique were inadequate, we had a few similar researches. In our study, we investagated the factors which might affect the clinical symptoms and death, especial HIV drug resistance'effect and guided for the antiretroviral therapy in our country.Objective1,To understand the factors associated with clinical symptoms among HAART treated HIV infections of first-line regimen in China2,To understand the factors associated with death among HAART treated HIV infections of first-line regimen in ChinaMethods1. A cross-sectional study was conducted among 28 provinces in China, in addition to Guizhou, Ningxia and Tibet from August 2006 to March 2007. All standard participants underwent a structured interview, and serum samples were collected. The questionnaire included demographics, situation of treatment, will of the medication, and situation of the taking. Laboratory test included immunology indicators (CD4 cell counts), virology indicators (viral load) and drug resistance indicators (genotype). The prevalence and association of clinical symptoms(disability due to AIDS last month, persistent fever intermittent or constant for longer than two weeks, chronic diarrhoea for longer than a week (loose stools more than 3 times every day) last month) were analyzed using Chi-square tests and multivariate Logistic regression model;2. Prospective cohort study: In the national free ART database, after HIV infections received HAART, they would be followed up at half a month, a month, two months, three months and then every three months, while the following-up forms were filled in. If a patient died, ending form would be filled in. The database of cross-sectional study included 2227 HIV infections and the national free ART database were connected by treatment code to achieve death toll, as of march 1, 2008. Sixteen HIV infections were not analysed because of missing treatment code .Trends in mortality was analyzed using Kaplan-Meier survival analysis and Cox regression analysis.Result1. There were 1062 patients achieving early first-line (AZT/DDI/NVP and D4T/DDI/NVP), accounted for 47.7%, 1165 patients achieving late first-line (AZT/3TC/NVP, D4T/3TC/NVP, AZT/3TC/EFV and D4T/3TC/EFV) treatment, accounted for 52.3%. Among initial early first-line treatment patients, the number of patients with disability due to AIDS last month was 15, which accounted for 1.4% of the total number of survey, the number of patients with persistent fever intermittent or constant for longer than two weeks last month was 82, which accounted for 7.7%, the number of patients with chronic diarrhoea for longer than one week(loose stools more than 3 times every day) last month was 83, which accounted for 7.8%, the number of patients with one of above three clinical symptoms last month was 140, which accounted for 13.2% of the total number of survey. Among initial late first-line treatment patients, the number of patients with disability due to AIDS last month was 41, which accounted for 3.5% , the number of patients with persistent fever intermittent or constant for longer than one month last month was 58, which accounted for 5.0%, the number of patients with chronic diarrhoea for longer than one week(loose stools more than 3 times every day) last month was 54, which accounted for 4.6%, the number of patients with one of above three clinical symptoms last month was 124, which accounted for 10.6% of the total number of survey. 2. In multivariate Logistic regression model, among initial early first-line (AZT/DDI/NVP and D4T/DDI/NVP) treatment patients,①missing drugs last 3 days (OR=2.85, 95%CI: 1.11~7.33, P=0.0296),②where to get drugs, getting drugs from county-level CDC or hospital (OR=0.41, 95%CI: 0.23~0.73, P=0.0025),③CD4 cell counts<200cells/ml(OR=1.70, 95%CI: 1.15~2.52, P=0.0078),④HIV drug resistance and viral load(in contrast with viral load<1000copy/μl, viral load≥1000copy/μl and HIV drug resistance OR=1.55, 95%CI: 1.01~2.37, P=0.0464) were significantly associated with clinical symptoms. Among initial late first-line (AZT/3TC/NVP, D4T/3TC/NVP, AZT/3TC/EFV and D4T/3TC/EFV) treatment patients,①missing drug last 3 day(sOR=3.10, 95%CI: 1.38~6.96, P=0.0060)②stop treatmen(tOR=5.70, 95%CI: 1.53~21.24, P=0.0095)③CD4 cell counts<200cells/ml(OR=1.66, 95%CI: 1.13~2.43, P=0.0096)were significantly associated with clinical symptoms.3. As of march 1, 2008, a total of 70 deaths were found. The mortality was 2.40 per 100 person-years (95% CI: 1.84~2.97); 61.4% were man; the mean of age is 40.9±8.8; 88.6% caused by AIDS.4. In the univariable Cox regression model, education, where to get drugs, the rate of taking antiviral drugs on time are greater than 90% last month, getting drugs interval, CD4 cell counts, HIV drug resistance and viral load, and stop treatment were significantly associated with death. In the multivariate Cox regression model①stop treatment(HR=2.21,95%CI:1.06~4.60, P=0.0350)②CD4 cell counts(in contrast with CD4≥350cells/ml, 200~350cells/ml(HR=2.63, 95%CI:1.01~6.85, P=0.0477), 100~200 cells/ml (HR=4.52, 95%CI:1.76~11.56, P=0.0017),<100 cells/ml (HR=17.73, 95%CI:7.32~42.93, P<0.0001)③HIV drug resistance and viral load (in contrast with viral load<1000 copy/μl, viral load≥1000 copy/μl and HIV drug resistance HR=2.12, 95%CI:1.21~3.71, P=0.0087)were significantly associated with death.Conclusion1. For the early first-line HAART regimen, missing drug last 3 days, CD4 cell counts<200cells/ml, HIV drug resistance and viral load≥1000copy/μl were risk factors associated with clinical symptoms,while getting drugs from county-level CDC or hospital freely was a protective factor. Among initial late first-line (AZT/3TC/NVP, D4T/3TC/NVP, AZT/3TC/EFV and D4T/3TC/EFV) treatment patients, missing drug last 3 days, stop treatment, CD4 cell counts<200cells/ml were risk factors associated with clinical symptoms.2. For the first-line ART regimen, stop treatment, low CD4 cell counts, HIV drug resistance and viral load≥1000copy/μl were significantly risk factors associated with death.