title: Impact of HIV-1, HIV-2, and HIV-1+2 dual infection on the outcome of tuberculosis.
abstract: BACKGROUND
  HIV-1 infection has been shown to impact the outcome of patients with tuberculosis (TB), but data regarding the impact of HIV-2 on TB outcomes are limited. The aim of this study was to assess the impact of HIV types on mortality among TB patients in Guinea-Bissau and to examine the predictive ability of the TBscoreII, a clinical score used to assess disease severity.
  
  
  METHODS
  In a prospective follow-up study, we examined the prevalence of HIV-1, HIV-2, and HIV-1+2 co-infection in TB patients in Guinea-Bissau, and the impact on outcomes at 12 months of follow-up. We included all adult TB patients in an observational TB cohort at the Bandim Health Project (BHP) in Guinea-Bissau between 2003 and 2013 and assessed survival status at 12 months after the start of treatment.
  
  
  RESULTS
  A total 1312 patients were included; 499 (38%) were female (male/female ratio 1.6). Three hundred and seventy-nine patients were HIV-infected: 241 had HIV-1, 93 had HIV-2, and 45 were HIV-1+2 dual infected. The HIV type-associated risk of TB was 6-fold higher for HIV-1, 7-fold higher for HIV-1+2 dual infection, and 2-fold higher for HIV-2 compared with the HIV-uninfected. Of the patients included, 144 (11%) died, 62 (12%) among females and 82 (9%) among males (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.64-1.30; p=0.596). Compared to male patients, female patients were younger (1 year younger, 95% CI 0.5-2; p=0.04), reported a longer duration of symptoms (14 days longer, 95% CI 4-25; p=0.003), and had a higher TBscoreII (0.5 points more, 95% CI 0.3-0.7; p<0.001). More females than males were HIV-infected (36% vs. 25%; p<0.001) and more females had a body mass index (BMI) <15 kg/m(2) (11% vs. 6%; p<0.001) and a mid upper arm circumference (MUAC) <200 mm (13% vs. 7%; p < 0.001). HIV infection increased the mortality risk, with HIV-1 infection displaying the highest HR (5.0, 95% CI 3.5-7.1), followed by HIV-1+2 (HR 4.2, 95% CI 2.2-7.8) and HIV-2 (HR 2.1, 95% CI 1.2-3.8). A TBscoreII ≥4 was associated with increased mortality (HR 2.2, 95% CI 1.5-3.1). Significantly increased HRs were found for signs of wasting; a BMI <18 kg/m(2) was associated with a HR of 1.8 (95% CI 1.3-2.6) and a MUAC <220 mm with a HR of 3.8 (95% CI 2.7-5.2).
  
  
  CONCLUSIONS
  The HIV type-associated risk of TB was much higher for HIV-1 patients and higher but less so for HIV-2 patients, compared with the HIV-uninfected. Clinical severity at presentation was also higher for HIV-infected patients, although less so for HIV-2-infected patients, and all HIV-infected patients had a poorer outcome than the uninfected; mortality was 4-5-fold higher for HIV-1 and dually infected patients and two-fold higher for HIV-2-infected patients. These differences between HIV types did not disappear after adjusting for CD4 count.
authors.affiliation: Bandim Health Project, INDEPTH Network, Statens Serum Institut, Bissau, Guinea-Bissau; GloHAU, Centre for Global Health, Department of Public Health, Aarhus University, Bartholins Alle 2, 8000 Aarhus C, Denmark. Electronic address: wejse@dadlnet.dk.
authors.forename: C
authors.initials: C
authors.lastname: Wejse
authors.affiliation: Bandim Health Project, INDEPTH Network, Statens Serum Institut, Bissau, Guinea-Bissau; Infectious Disease Research Unit, Aarhus University Hospital, Skejby, Denmark.
authors.forename: C B
authors.initials: CB
authors.lastname: Patsche
authors.affiliation: Infectious Disease Research Unit, Aarhus University Hospital, Skejby, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Kühle
authors.affiliation: Hospital Raoul Follereau, Hospital Nacionál de Tuberculosis, Bissau, Guinea-Bissau.
authors.forename: F J V
authors.initials: FJ
authors.lastname: Bamba
authors.affiliation: Hospital Raoul Follereau, Hospital Nacionál de Tuberculosis, Bissau, Guinea-Bissau.
authors.forename: M S
authors.initials: MS
authors.lastname: Mendes
authors.affiliation: Bandim Health Project, INDEPTH Network, Statens Serum Institut, Bissau, Guinea-Bissau; Infectious Disease Research Unit, Aarhus University Hospital, Skejby, Denmark.
authors.forename: G
authors.initials: G
authors.lastname: Lemvik
authors.affiliation: Bandim Health Project, INDEPTH Network, Statens Serum Institut, Bissau, Guinea-Bissau.
authors.forename: V F
authors.initials: VF
authors.lastname: Gomes
authors.affiliation: Bandim Health Project, INDEPTH Network, Statens Serum Institut, Bissau, Guinea-Bissau; Department of Infectious Diseases, Hvidovre University Hospital, Copenhagen, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Rudolf
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060085:Coinfection / Q000453:epidemiology / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006169:Guinea-Bissau / Q000453:epidemiology; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology; D015497:HIV-1; D015498:HIV-2; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D016896:Treatment Outcome; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality*; D055815:Young Adult
keywords: HIV-1; HIV-2; Mortality; Tuberculosis