Opportunistic infections (OIs) cause significant morbidity/mortality in human immunodeficiency virus (HIV) infected individuals globally. Disparities between high income countries (HICs) and low/middle income countries (LMICs) in the magnitude of HIV related OIs in pre-highly active antiretroviral therapy (HAART) populations was reviewed, and HAART induced decline in OIs was further compared between the two settings. Studies published in English from onset of HIV epidemic up to December 2013 were searched in PubMed, Google, Google Scholar, and African Journal online. An article was included if (a) the study was conducted in HIC or LMIC, (b) the age of the participants was ≥12 years, (c) the HAART status of the participants was stated, and (d) various types of OIs were investigated. In predominantly pre HAART populations, the incidence and prevalence of overall HIV related OIs in HIC ranged from 5.5 to 50.0 per 100 person years (PY) and 27.4–56.7%, respectively. In LMIC, the respective overall incidence and prevalence of OIs were 12.2–93.9 per 100 PY and 32.0–77.7%. Pneumocystis jirovecii pneumonia, candidiasis, Cytomegalovirus disease, Mycobacterium avium complex disease, and Kaposi’s sarcoma were the most frequent OIs in HICs while tuberculosis, candidiasis, chronic diarrhea, and cryptococcosis were predominant in LMICs. The introduction of HAART led to substantial reduction in the incidence of OIs with more impressive percentage decline in HICs (43–97%) compared to 30–79% in LMICs. Disparities in the magnitude of HIV related OIs between HICs and LMICs are evident both in the pre HAART and post HAART era. Efforts to optimize HAART induced decline in HIV related OIs should become a global health priority irrespective of prevailing socioeconomic circumstances.
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