Laboratory and clinical predictors of disease progression following initiation of combination therapy in HIV-infected adults in Thailand

• Published in: PloS one Vol. 7; no. 8; p. e43375
• Main Authors: Duong, Trinh, Jourdain, Gonzague, Ngo-Giang-Huong, Nicole, Le Cœur, Sophie, Kantipong, Pacharee, Buranabanjasatean, Sudanee, Leenasirimakul, Prattana, Ariyadej, Sriprapar, Tansuphasawasdikul, Somboon, Thongpaen, Suchart, Lallemant, Marc
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15-08-2012; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; Adults; AIDS; Anemia; Anti-HIV Agents - pharmacology; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Care and treatment; CD4 antigen; CD4-Positive T-Lymphocytes - cytology; Cell death; Cell survival; Cohort Studies; Combination therapy; Death; Development and progression; Diagnosis; Diagnostic systems; Disease control; Disease Progression; Female; Follow-Up Studies; Health risks; Hemoglobin; Hemoglobins; Highly active antiretroviral therapy; HIV; HIV infections; HIV Infections - drug therapy; HIV patients; Human immunodeficiency virus; Humans; Immunosuppression; Income; Male; Medical prognosis; Medical research; Medicine; Monitoring; Mortality; Mortality risk; Multivariate Analysis; Patients; Poisson density functions; Poisson Distribution; Prevention; Regression analysis; Risk; Statistical analysis; Thailand; Therapy; Tuberculosis; Viral Load; Thailand; France; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0043375

Data on determinants of long-term disease progression in HIV-infected patients on antiretroviral therapy (ART) are limited in low and middle-income settings.
Effects of current CD4 count, viral load and haemoglobin and diagnosis of AIDS-defining events (ADEs) after start of combination ART (cART) on death and new ADEs were assessed using Poisson regression, in patient aged ≥ 18 years within a multi-centre cohort in Thailand.
Among 1,572 patients, median follow-up from cART initiation was 4.4 (IQR 3.6-6.3) years. The analysis of death was based on 60 events during 6,573 person-years; 30/50 (60%) deaths with underlying cause ascertained were attributable to infections. Analysis of new ADE included 192 events during 5,865 person-years; TB and Pneumocystis jiroveci pneumonia were the most commonly presented first new ADE (35% and 20% of cases, respectively). In multivariable analyses, low current CD4 count after starting cART was the strongest predictor of death and of new ADE. Even at CD4 above 200 cells/mm(3), survival improved steadily with CD4, with mortality rare at ≥ 500 cells/mm(3) (rate 1.1 per 1,000 person-years). Haemoglobin had a strong independent effect, while viral load was weakly predictive with poorer prognosis only observed at ≥ 100,000 copies/ml. Mortality risk increased following diagnosis of ADEs during cART. The decline in mortality rate with duration on cART (from 21.3 per 1,000 person-years within first 6 months to 4.7 per 1,000 person-years at ≥ 36 months) was accounted for by current CD4 count.
Patients with low CD4 count or haemoglobin require more intensive diagnostic and treatment of underlying causes. Maintaining CD4 ≥ 500 cells/mm(3) minimizes mortality. However, patient monitoring could potentially be relaxed at high CD4 count if resources are limited. Optimal ART monitoring strategies in low-income settings remain a research priority. Better understanding of the aetiology of anaemia in patients on ART could guide prevention and treatment.