HIV This Week

The ART-LINC Collaboration of the International Databases to Evaluate AIDS (IeDEA). Antiretroviral therapy in resource-limited settings 1996 to 2006: patient characteristics, treatment regimens and monitoring in sub-Saharan Africa, Asia and Latin America. Trop Med Int Health. 2008;13(7):870-9

The collaboration set out to describe temporal trends in baseline clinical characteristics, initial treatment regimens, and monitoring of patients starting antiretroviral therapy in resource-limited settings. The collaborators analysed data from 17 antiretroviral therapy programmes in 12 countries in sub-Saharan Africa, South America and Asia.  Patients aged 16 years or older with documented date of start of highly active antiretroviral therapy were included. Data were analysed by calculating medians, interquartile ranges and percentages by regions and time periods. Not all centres provided data for 2006 and therefore 2005 and 2006 were combined. A total of 36 715 patients who started antiretroviral therapy 1996-2006 were included in the analysis. Patient numbers increased substantially in sub-Saharan Africa and Asia, and the number of initial regimens declined, to four and five, respectively, in 2005-2006. In South America 20 regimes were used in 2005-2006. A combination of 3TC/D4T/NVP was used for 56% of African patients and 42% of Asian patients; AZT/3TC/EFV was used in 33% of patients in South America. The median baseline CD4 count increased in recent years, to 122 cells/mul (interquartile range 53-194) in 2005-2006 in Africa, 134 cells/mul (interquartile range 72-191) in Asia, and 197 cells/mul (interquartile range 61-277) in South America, but 77%, 78% and 51%, respectively, started with <200 cells/mul in 2005-2006. In all regions baseline CD4 cell counts were higher in women than men: differences were 22cells/mul in Africa, 65 cells/mul in Asia and 10 cells/mul in South America. In 2005-2006 a viral load at 6 months was available in 21% of patients Africa, 8% of Asian patients and 73% of patients in South America.  Corresponding figures for 6-month CD4 cell counts were 74%, 77% and 81%.  The public health approach to providing ART proposed by the World Health Organization has been implemented in sub-Saharan Africa and Asia. Although CD4 cell counts at the start of ART have increased in recent years, most patients continue to start with counts well below the recommended threshold. Particular attention should be paid to more timely initiation of ART in HIV-infected men.

Editors´note: This database of HIV-infected patients followed clinically in resource-limited settings permits valuable analyses of trends over time in the scale-up of the public health approach to antiretroviral treatment. Standardised first-line and second-line regimens, simplified decision making, and standardised clinical and laboratory monitoring are key features of this approach. Although patients in South America are starting on treatment with less severe immunodeficiency, the majority of African and Asian patients are starting late, which has important implications both for early mortality and for more rapid disease progression.

Hallett TB, Gregson S, Dube S, Garnett GP. The Impact of Monitoring HIV Patients Prior to Treatment in Resource-Poor Settings: Insights from Mathematical Modelling. PLoS Med. 2008;5(3):e53

The roll-out of antiretroviral treatment in developing countries concentrates on finding patients currently in need, but over time many HIV-infected individuals will be identified who will require treatment in the future. Hallett and colleagues investigated the potential influence of alternative patient management and antiretroviral treatment initiation strategies on the impact of antiretroviral treatment programmes in sub-Saharan Africa. They developed a stochastic mathematical model representing disease progression, diagnosis, clinical monitoring, and survival in a cohort of 1,000 hypothetical HIV-infected individuals in Africa. If individuals primarily enter antiretroviral treatment programmes when symptomatic, the model predicts that only 25% will start treatment and, on average, 6 life-years will be saved per person treated. If individuals are recruited to programmes while still healthy and are frequently monitored, and CD4(+) cell counts are used to help decide when to initiate antiretroviral treatment, three times as many are expected to be treated, and average life-years saved among those treated increases to 15. The impact of programmes can be improved further by performing a second CD4(+) cell count when the initial value is close to the threshold for starting treatment, maintaining high patient follow-up rates, and prioritising monitoring the oldest (>/= 35 y) and most immune-suppressed patients (CD4(+) cell count </= 350). Initiating antiretroviral treatment at higher CD4(+) cell counts than the World Health Organization recommends leads to more life-years saved, but disproportionately more years spent on antiretroviral treatment. The authors conclude that the overall impact of antiretroviral treatment programmes will be limited if rates of diagnosis are low and individuals enter care too late. Frequently monitoring individuals at all stages of HIV infection and using CD4 cell count information to determine when to start treatment can maximise the impact of ART.

Editors´note: This modelling work demonstrates that measuring CD4 cells frequently will save more life-years because it can trigger the start of antiretroviral treatment before the immune system is irreversibly damaged. In resource-limited settings, more life years can be saved per year on antiretroviral treatment by frequent CD4 cell count measurements. Therefore, there are strong arguments in favour of improved patient monitoring even before treatment initiation.