: CD4 cell count in adults with human immunodeficiency virus (HIV) infection (PLHIV) not receiving antiretroviral therapy (ART) influences tuberculosis (TB) risk. Despite widespread use in models informing resource allocation, this relationship has not been systematically reviewed. Methods : We systematically searched MEDLINE, Aids Info, Cochrane review database and Google Scholar for reports in English describing TB incidence stratified by updated CD4 cell count in cohorts of HIV-positive

more »

... s (age >=15 years) not on ART (PROSPERO protocol no: CRD42016048888). Among inclusion criteria were: reporting precision for TB incidence, repeated CD4 measurements, and TB incidence reported for those not on ART or monotherapy. Study quality was assessed via the Newcastle-Ottawa tool for cohort studies. A Bayesian hierarchical model was fitted to estimate the pooled factor increase in TB incidence with respect to CD4 cell count decrement. Results : 1,555 distinct records were identified from which 164 full text articles were obtained. Common reasons for exclusion of full texts were: no valid TB incidence, no repeat CD4 measurements, and not reporting TB incidence by ART status. The 7 studies included reported on 1,206 TB cases among 41,271 individuals, with a typical median follow-up of 4 years. Studies were generally rated as moderate or high quality. Our meta-analysis estimated a 1.43 (95% credible interval: 1.16 -1.88)-fold increase in TB incidence per 100 cells per mm 3 decrease in CD4 cell count. Discussion : Our analysis confirms previous estimates of exponential increase in TB incidence with declining CD4 cell count in adults, emphasizing the importance of early ART initiation to reduce TB risk in PLHIV. PeerJ reviewing PDF | (Abstract 14 Background: CD4 cell count in adults with human immunodeficiency virus (HIV) infection 15 (PLHIV) not receiving antiretroviral therapy (ART) influences tuberculosis (TB) risk. Despite 16 widespread use in models informing resource allocation, this relationship has not been 17 systematically reviewed. 18 19 Methods: We systematically searched MEDLINE, Aids Info, Cochrane review database and 20 Google Scholar for reports in English describing TB incidence stratified by updated CD4 cell 21 count in cohorts of HIV-positive adults (age >=15 years) not on ART (PROSPERO protocol no: 22 CRD42016048888). Among inclusion criteria were: reporting precision for TB incidence, 23 repeated CD4 measurements, and TB incidence reported for those not on ART or monotherapy. 24 Study quality was assessed via the Newcastle-Ottawa tool for cohort studies. A Bayesian 25 hierarchical model was fitted to estimate the pooled factor increase in TB incidence with respect 26 to CD4 cell count decrement. 27 28 Results: 1,555 distinct records were identified from which 164 full text articles were obtained. 29 Common reasons for exclusion of full texts were: no valid TB incidence, no repeat CD4 30 measurements, and not reporting TB incidence by ART status. The 7 studies included reported 31 on 1,206 TB cases among 41,271 individuals, with a typical median follow-up of 4 years. 32 Studies were generally rated as moderate or high quality. Our meta-analysis estimated a 1.43 33 (95% credible interval: 1.16 -1.88)-fold increase in TB incidence per 100 cells per mm 3 34 decrease in CD4 cell count. 35 Discussion: Our analysis confirms previous estimates of exponential increase in TB incidence 36 with declining CD4 cell count in adults, emphasizing the importance of early ART initiation to 37 reduce TB risk in PLHIV. 38 39 40