Immunodeficiency at the Start of Combination Antiretroviral Therapy in Low-, Middle-, and High-Income Countries

Abstract

Objectives To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC) and high-income (HIC) countries. Methods Patients aged ≥16 years starting cART in a clinic participating in a multi-cohort collaboration spanning six continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multi-level linear regression models were adjusted for age, gender and calendar year; missing CD4 counts were imputed. Findings 379,865 patients from nine LIC, four LMIC, four UMIC and six HIC were included. In LIC the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/μl between 2002 and 2009. Corresponding increases in LMIC, UMIC and HIC were from 87 to 155 cells/μl (76% increase), 88 to 135 cells/μl (53%) and 209 to 274 cells/μl (31%). In 2009, compared to LIC, median counts were 13 cells/μl (95% CI -56 to +30) lower in LMIC, 22 cells/μl (-62 to +18) lower in UMIC and 112 /μl (+75 to +149) higher in HIC. They were 23 cells/μl (95% CI +18 to +28) higher in women than men. Median counts were 88 cells/μl (95% CI +35 to +141) higher in countries with an estimated national cART coverage >80%, compared to countries with <40% coverage. Conclusions Median CD4 cell counts at start of cART increased 2000-2009 but remained below 200 cells/μl in LIC and MIC and below 300 cells/μl in HIC. Earlier start of cART will require substantial efforts and resources globally.

Trends in and correlates of CD4+ cell count at antiretroviral therapy initiation after changes in national ART guidelines in Rwanda

“…Surprisingly, although this was an analysis of specific HIV sites in an urban setting, our reported median CD4 + cell count at ART initiation reached up to 293 cells/µl in 2011, and is considerably higher than the recent estimates of median CD4 + of 155 cells/µl in 2009 from clinical sites in various LMICs [18]. Therefore, our observation of higher median CD4 + cell count at ART initiation is different from the consistently reported low median CD4 + cell count at ART initiation in other SSA settings [3,4,7–10].…”

“…The median CD4 + cell count at ART initiation in our study of HIV-infected Rwandan patients is higher than reported in other studies in the region [10,15,16]. A global analysis of data from 48 countries, including those in North America, Europe, and SSA, found that in 2009 the United States had the highest mean CD4 + cell count at ART initiation (307 cells/µl) followed, remarkably, by Rwanda (287 cells/µl) [17,18]. Given this and other HIV programmatic scale-up successes in Rwanda [13,14,19], there are likely important lessons to be learned by comparing Rwanda’s experience with those of other countries in SSA.…”

HIV infection and immune activation

“…Despite concrete evidence that HIV infection should be treated upon diagnosis even at CD4 T cell counts above 500 cells/μL [7], the sobering reality is that many patients present late at diagnosis or treatment initiation in both resource limited and resource rich settings [8]. According to US statistics, 23% of patients get diagnosed with HIV at stage 3 (AIDS) [9] and recent studies from South Africa [10] and Europe [11] report similar statistics with a persistently high proportion of patients presenting late for therapy initiation.…”

Implementation and Operational Research

“…Mortality in the first year on ART was as high as 40%, with the majority of deaths occurring in the first three months after ART initiation [3–5]. Patients with the lowest CD4 T-cell counts have the highest mortality risk [5–11], and despite expanded voluntary HIV counseling and testing efforts, many patients still present with advanced immunosuppression [12–15]. …”