Rollout of antiretroviral therapy (ART) in low and middle income countries has averted over 850 000 cases of HIV-related opportunistic infections at a saving of at least $47m per year, according to a systematic review and meta-analysis. Incidence of opportunistic infections (OIs) declined by between 57%-91% in the first year after starting ART, with the greatest reductions in cases of oral thrush, toxoplasmosis and PCP pneumonia.
“Our analyses…provide a valuable approximation of the number of OIs averted, and potential cost savings of $47m per annum, from initiating ART before CD4 count declines to less than 200 cells/mm3”, comment the authors. “These estimates likely underestimate the full savings as they do not capture variation in treatment costs across different countries, or include the diagnostic costs. Although the costs of ART tend to be higher than the costs of treating OIs, the savings from averting these OIs are a substantial additional benefit of ART.”
The impact of ART on the incidence of OIs in resource rich countries is well documented. Most patients taking HIV therapy in such settings now have a normal or near-normal life expectancy and liver disease, cardiovascular disease and non-Aids-related cancers are now the leading cause of illness and death, rather than OIs. However, less is known about the impact of ART on the incidence of OIs in low and middle income countries.
An international team of investigators therefore conducted a systematic review and meta-analysis of relevant research to determine how many OIs have been averted by ART in sub-Saharan Africa, Asia and Latin America and the Caribbean.
Studies reporting on OI incidence in HIV-positive adults between 1990 and 2013 were eligible for inclusion in the analysis. Incidence of OIs was calculated pre-ART, during the first year after initiating ART and during longer-term ART. The authors assumed ART was started at a CD4 cell count of 200 cells/mm3 or when a patient developed serious HIV-related illnesses. The 13 most common HIV-related OIs were considered, including oral and oesophageal thrush, PCP pneumonia, toxoplasmosis, CMV, bacterial pneumonia and tuberculosis (TB).
A search identified 126 eligible studies. These were conducted in 38 countries and involved approximately 500,000 patients, over 400,000 of who were in sub-Saharan Africa. Study size ranged from 54 to 175,212 participants (median 765) and length of follow-up ranged between three and 78 months (median 24 months).
In ART-naïve patients, the most common OIs were oral thrush (19%), TB in unspecified sites (10%), herpes zoster (9%), pulmonary TB (9%), bacterial pneumonia (6%) and genital ulcerate disease (6%).
During the first year after ART initiation, the risk of all OIs declined to less than 2%, except for unspecified TB (4%), pulmonary TB (4%), herpes zoster (2.3%) and oral thrush (2.3%), which remained the most common OIs.
The greatest effect of ART was seen during the first year of therapy, when the risk of OIs was reduced by between 57% and 91%. The effect was greatest for oral thrush (91%), toxoplasmosis (88%) and PCP (87%). There was a 57% to 64% reduction in the risk of unspecified TB (57%) and pulmonary TB (62%).
After the first year of ART, there was a further reduction in the risk of pulmonary TB (87%) and unspecified TB (74%). There was also a reduction in the risk of other OIs, though less marked than during the first year of treatment.
The use of ART before CD4 cell count declined to 200 cells/mm3 was estimated to have averted 857,828 OI cases, most of which (599,711) were in sub-Saharan Africa.
Estimated cost savings in OI treatment in 2013 were $46.7m. Most of the saving from ART use was due to averted cases of TB, where an estimated $33.3m was saved.
“The profound effect of ART in the incidence of most HIV-related OIs is the key reason for the observed global decline in HIV-related mortality, and highlights the continued priority of expanding ART access,” conclude the authors. “It is estimated that expanding ART to all people living with HIV will avert 21m Aids-related deaths by 2030.”
Background: To understand regional burdens and inform delivery of health services, we conducted a systematic review and meta-analysis to evaluate the effect of antiretroviral therapy (ART) on incidence of key opportunistic infections (OIs) in HIV-infected adults in low and middle-income countries (LMIC).
Methods: Eligible studies describing the cumulative incidence of OIs and proportion on ART from 1990 to November 2013 were identified using multiple databases. Summary incident risks for the ART-naïve period, and during and after the first year of ART, were calculated using random effects meta-analyses. Summary estimates from ART subgroups were compared using meta-regression. The number of OI cases and associated costs averted if ART was initiated at CD4 ≥200 cells/μl was estimated using UNAIDS country estimates and global average OI treatment cost per case.
Results: We identified 7,965 citations, and included 126 studies describing 491,608 HIV-infected persons. In ART-naïve patients, summary risk was highest (>5%) for oral candidiasis, tuberculosis, herpes zoster, and bacterial pneumonia. The reduction in incidence was greatest for all OIs during the first 12 months of ART (range 57-91%) except for tuberculosis, and was largest for oral candidiasis, PCP and toxoplasmosis. Earlier ART was estimated to have averted 857,828 cases in 2013 (95% confidence interval [CI], 828,032-874,853), with cost savings of $46.7 million (95% CI, 43.8-49.4).
Conclusions: There was a major reduction in risk for most OIs with ART use in LMICs, with the greatest effect seen in the first year of treatment. ART has resulted in substantial cost savings from OIs averted.