HIV This Week

Phillips AN, Pillay D, Miners AH, Bennett DE, Gilks CF, Lundgren JD. Outcomes from monitoring of patients on antiretroviral therapy in resource-limited settings with viral load, CD4 cell count, or clinical observation alone: a computer simulation model. Lancet. 2008 ;371(9622):1443-51.

In lower-income countries, the World Health Organization (WHO) recommends a population-based approach to antiretroviral treatment with standardized regimens and clinical decision making based on clinical status and, where available CD4 cell count, rather than viral load. Phillips and colleagues aimed to study the potential consequences of such monitoring strategies, especially in terms of survival and resistance development. A validated computer simulation model of HIV infection and the effect of antiretroviral therapy was used to compare survival, use of second-line regimens, and development of resistance that result from different strategies-based on viral load, CD4 cell count, or clinical observation alone-for determining when to switch people starting antiretroviral treatment with the WHO-recommended first-line regimen of stavudine, lamivudine, and nevirapine to second-line antiretroviral treatment. Over 5 years, the predicted proportion of potential life-years survived was 83% with viral load monitoring (switch when viral load >500 copies per mL), 82% with CD4 cell count monitoring (switch at 50% drop from peak), and 82% with clinical monitoring (switch when two new WHO stage 3 events or a WHO stage 4 event occur). Corresponding values over 20 years were 67%, 64%, and 64%. Findings were robust to variations in model specification in extensive univariable and multivariable sensitivity analyses. Although survival was slightly longer with viral load monitoring, this strategy was not the most cost effective. For patients on the first-line regimen of stavudine, lamivudine, and nevirapine the benefits of viral load or CD4 cell count monitoring over clinical monitoring alone are modest. Development of cheap and robust versions of these assays is important, but widening access to antiretrovirals-with or without laboratory monitoring-is currently the highest priority.

Editors’ note: This mathematical modelling demonstrates that lack of access to laboratory monitoring with CD4 counts or viral load should not hinder antiretroviral treatment scale-up. Relying on clinical monitoring alone does not have marked detrimental effects on patient survival or development of resistance. However, precise definitions of clinical failure and specific training materials are needed to improve detection and diagnosis of the conditions that suggest that a switch to second-line treatment is necessary.

The response to treatment and risk factors for early mortality following initiation of combination antiretroviral therapy in a cohort of African patients are described in a retrospective cohort design. Medical history, laboratory parameters, and mortality data were reviewed for patients initiating antiretroviral therapy in 12 clinical centres in Mozambique , Tanzania, and Malawi. Among 3456 HIV-1-infected patients who received antiretroviral therapy for more than 6 months, at baseline 72% had WHO clinical stages 3/4, 7% had a viral load <400 copies/ml, and 38% had a CD4 cell count >200/mm3. One year later, 78% had undetectable virus loads and 79% had CD4 cell counts >200 cells/mm3. In the first year of antiretroviral therapy 260 deaths occurred (97 per 1000 person/years) with mortality peaking in the first 3 months. The highest mortality was observed in patients with low body mass index, low haemoglobin levels, and CD4 values <200 cells/mm3 at baseline. Mortality rates following initiation of antiretroviral therapy are higher in patients in resource-limited areas, particularly in the first 90 days following treatment initiation. Antiretroviral therapy initiated at higher CD4 cell count levels, especially among malnourished and/or anaemic patients, will carry significant public health impact.

Editors’ note: Mortality in the initial months of starting antiretroviral treatment is higher in resource-limited than in high-income settings, even when controlling for CD4 count at treatment initiation. This is likely due to higher prevalence of co-infections such as malaria, low haemoglobin (anaemia), and body mass indices below 18 (malnutrition). Mortality could be reduced by treating anaemia, malnutrition, and co-infections, and by starting antiretroviral treatment earlier in people with these co-morbidities.