Purpose of review: To summarize the recent findings on long-term (at least 3-4 years) immunological responses to combination antiretroviral therapy (cART) and to compare and contrast the findings between cohorts from high-income and low-middle income countries (LMICs).
Recent findings: Cohort studies from high-income settings suggest that a majority of treated HIV-infected patients who maintain suppressed HIV viremia experience a gradual increase in CD4 cell counts for several years to normal levels. However, those who start cART at CD4 cell counts less than 200 cells/μl (as opposed to CD4 cell counts>200 cells/μl) spend several more years below the safe CD4 cell count threshold of 500 cells/μl. Cohorts from LMICs also report persistent improvements in CD4+ cell counts over first 4-5 years of follow-up. However, low-CD4 cell counts (<200 cells/μl) at the start of cART, high early mortality, and loss to follow-up in LMICs settings suggest that the observed optimistic responses may be affected by survivorship bias and should be cautiously interpreted as the optimal, rather than an average, response in LMICs populations.
Summary: LMICs cohorts report similar immunological responses to cART as high-income countries in first 4-5 years of follow-up. Sustaining success in these settings is dependent on timely access to first-line and future cART options, efforts to reduce loss to follow-up, and implementation of treatment guidelines. Cohorts from LMICs are encouraged to continue improving treatment programs and to continue reporting outcomes over the next decade, as surveillance for potential future blunting in responses.