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

Abstract

Background: Data on determinants of long-term disease progression in HIV-infected patients on antiretroviral therapy (ART) are limited in low and middle-income settings.

Methods: 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.

Results: 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.

Conclusions: 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.

Figure 1. Distribution of CD4 count (A), viral load (B) and haemoglobin (C) over time from initiation of cART.

The closest measurement to each nominal time points within a±3 months window was selected for each patient.

Figure 2. Distribution of most recent CD4 count (A), viral load (B) and haemoglobin (C) measurement at time of death, by cause of death.

Based measurements within the last 9 months before date of death. Number of cases by cause of death: 10 TB, 20 other infections, 20 not related to infection and 10 not known.