Relevant Gender Differences in Epidemiological Profile,Exposure to First Antiretroviral Regimen and Survival in the Spanish Aids Research Network Cohort

Abstract

Background

The possible differences in the disease spectrum and prognosis of HIV infection in women and men is a major point of concern. Women are under-represented in randomized clinical trials and in some cohorts. Discordant results have often been obtained depending on the setting.

Methods

We assessed gender differences in clinical and epidemiological features, antiretroviral treatment (ART) exposure and survival in two multicentre cohorts of HIV-positive subjects in Spain: CoRIS-MD and CoRIS. Competing risk regression models were used to assess gender effect on time to start ART and time to first ART change, and a Cox regression model to estimate gender effect on time to death.

Results

Between January 1996 and December 2008, 1,953 women and 6,072 men naive to ART at study entry were included. The trend analysis over time showed the percentage of women in the younger (<20 years) and older (>50 years) strata increased significantly (P<0.001) from 0.5% and 1.8% in 1996 to 4.9% and 4.2% in 2008, respectively. By competing risk analysis women started ART earlier than men (adjusted subhazard ratio [ASHR] 1.21, 95% CI 1.11, 1.31) in CoRIS cohort, while in CoRIS-MD none of these differences were observed. In both cohorts women showed a shorter time to the first ART change (ASHR 1.10, 95% CI 1.01, 1.19). Pregnancy and patient's/physician's decisions as reasons for changing were more frequent in women than in men in CoRIS. In the Cox regression model, gender was not associated with differences in survival.

Conclusions

In two large cohorts in Spain, we observed relevant gender differences in epidemiological characteristics and antiretroviral exposure outcomes, while survival differences were not attributable to gender.

References

UNAIDS. Report on the global AIDS epidemic. 2010 edition. (Accessed 10 April 2012.) Available from http://www.unaids.org/globalreport/Global_report.htm.

Sordo del Castillo

, Ruiz-Pérez

, Olry de Labry Lima

Biological, psychosocial, therapeutic and quality of life inequalities between HIV-positive men and women - a review from a gender perspective. AIDS Rev 2010; 12: 113–120.

Gibbs

Understandings of gender and HIV in the South African media. AIDS Care 2010; 22 Suppl 2: 1620–1628.

Mboi

Women and AIDS in south and South-East Asia: the challenge and the response. World Health Stat Q 1996; 49: 94–105.

Newman

C.J.

, Fogarty

, Makoae

L.N.

, Reavely

Occupational segregation, gender essentialism and male primacy as major barriers to equity in HIV/AIDS caregiving: findings from Lesotho. Int J Equity Health 2011; 10: 24.

Gibbs

Understandings of gender and HIV in the South African media. AIDS Care 2010; 22 Suppl 2: 1620–1628.

Carael

, Marais

, Polsky

, Mendoza

Is there a gender gap in the HIV response? Evaluating national HIV responses from the United Nations General Assembly Special Session on HIV/AIDS country reports. J Acquir Immune Defic Syndr 2009; 52 Suppl 2: S111–S118.

Huang

J.S.

, Harrity

, Lee

, Becerra

, Santos

, Mathews

W.C.

Body image in women with HIV: a cross-sectional evaluation. AIDS Res Ther 2006; 3: 17.

Koenig

L.J.

, McCree

D.H.

Gender-responsive programming and HIV prevention for women: Centers for Disease Control and Prevention perspective. Womens Health Issues 2011; 21 Suppl 6: S241–S242.

10.

d'Arminio Monforte

, González

, Haberl

Better mind the gap: addressing the shortage of HIV-positive women in clinical trials. AIDS 2010; 24: 1091–1094.

11.

Braga

, Cardoso

M.R.

, Segurado

A.C.

Gender differences in survival in an HIV/AIDS cohort from San Paulo, Brazil. AIDS Patient Care STDS 2007; 21: 321–328.

12.

Melnick

S.L.

, Sherer

, Louis

T.A.

Survival and disease progression according to gender of patients with HIV infection. The Terry Beirn Community Programs for Clinical Research on AIDS. JAMA 1994; 272: 1915–1921.

13.

Alibhai

, Kipp

, Saunders

L.D.

Gender-related mortality for HIV-infected patients on highly active antiretroviral therapy (HAART) in rural Uganda. Int J Womens Health 2010; 2: 45–52.

14.

Moore

A.L.

, Sabin

C.A.

, Johnson

M.A.

, Phillips

A.N.

Gender and clinical outcomes after starting highly active antiretroviral treatment: a cohort study. J Acquir Immune Defic Syndr 2002; 29: 197–202.

15.

Pérez-Hoyos

, del Amo

, Muga

Effectiveness of highly active antiretroviral therapy in Spanish cohorts of HIV seroconverters: differences by transmission category. AIDS 2003; 17: 353–359.

16.

Nicastri

, Angeletti

, Palmisano

Gender differences in clinical progression of HIV-1-infected individuals during long-term highly active antiretroviral therapy. AIDS 2005; 19: 577–583.

17.

Jarrin

, Geskus

, Bhaskaran

Gender differences in HIV progression to AIDS in industrialized countries: slower disease progression following HIV seroconversion in women. Am J Epidemiol 2008; 168: 532–540.

18.

Mocroft

, Gill

M.J.

, Davidson

, Phillips

A.N.

Are there gender differences in starting protease inhibitors, HAART, and disease progression despite equal access to care?

J Acquir Immune Defic Syndr 2000; 24: 475–482.

19.

Collazos

, Asensi

, Cartón

J.A.

Sex differences in the clinical, immunological and virological parameters of HIV-infected patients treated with HAART. AIDS 2007; 21: 835–843.

20.

Gandhi

, Bacchetti

, Miotti

, Quinn

T.C.

, Veronese

, Greenblatt

R.M.

Does patient sex affect human immunodeficiency virus levels?

Clin Infect Dis 2002; 35: 313–322.

21.

Fowler

M.G.

, Melnick

S.L.

, Mathieson

B.J.

Women and HIV. Epidemiology and global overview. Obstet Gynecol Clin North Am 1997; 24: 705–729.

22.

Nicolosi

, Corrêa Leite

M.L.

, Musicco

, Arici

, Gavazzeni

, Lazzarin

The efficiency of male-to-female and female-to-male sexual transmission of the human immunodeficiency virus: a study of 730 stable couples. Epidemiology 1994; 5: 570–575.

23.

Perez-Hoyos

, Rodríguez-Arenas

M.A.

, García de la Hera

Progression to AIDS and death and response to HAART in men and women from a multicenter hospital-based cohort. J Womens Health (Larchmt) 2007; 16: 1052–1061.

24.

García de la Hera

, Ferreros

, del Amo

Gender differences in progression to AIDS and death from HIV seroconversion in a cohort of injecting drug users. J Epidemiol Community Health 2004; 58: 944–950.

25.

Gwadz

M.V.

, Leonard

N.R.

, Nakagawa

Gender differences in attitudes toward AIDS clinical trials among urban HIV-infected individuals from racial and ethnic minority backgrounds. AIDS Care 2006; 18: 786–794.

26.

Caro-Murillo

A.M.

, Castilla

, Pérez-Hoyos

[Spanish cohort of naive HIV-infected patients (CoRIS): rationale, organization and initial results]. Enferm Infecc Microbiol Clin 2007; 25: 23–31. Spanish.

27.

Sobrino-Vegas

, Gutiérrez

, Berenguer

[The Cohort of the Spanish HIV Research Network (CORIS) and its associated biobank; organizational issues, main findings and losses to follow-up]. Enferm Infecc Microbiol Clin 2011; 29: 645–653. Spanish.

28.

Fine

J.P.

, Gray

R.J.

A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496–509.

29.

Simone

M.J.

, Appelbaum

HIV in older adults. Geriatrics 2008; 63: 6–12.

30.

Manfredi

HIV infection and advanced age emerging epidemiological, clinical, and management issues. Ageing Res Rev 2004; 3: 31–54.

31.

Gebo

K.A.

HIV and aging: implications for patient management. Drugs Aging 2006; 23: 897–913.

32.

European Centre for Disease Prevention and Control/WHO Regional Office for Europe. HIV/AIDS surveillance in Europe 2009. Stockholm: European Centre for Disease Prevention and Control; 2010. (Accessed 1 March 2012.) Available from http://ecdc.europa.eu/en/publications/Publications/101129_SUR_HIV_2009.pdf.

33.

Caro-Murillo

A.M.

, Gil Luciano

, Navarro Rubio

, Leal Noval

, Blanco Ramos

J.R.

HIV infection in different age groups: potential implications for prevention. CoRIS Cohort, Spain, 2004–2008. Med Clin (Barc) 2010; 134: 521–527.

34.

Gandhi

, Bacchetti

, Miotti

, Quinn

T.C.

, Veronese

, Greenblatt

R.M.

Does patient sex affect human immunodeficiency virus levels?

Clin Infect Dis 2002; 35: 313–322.

35.

Panel of members of the Gesida AIDS Study Group and the Spanish AIDS Plan. [National consensus document by GESIDA/National AIDS Plan on antiretroviral treatment in adults infected by the human immunodeficiency virus (January 2011 update)]. Spanish. (Updated January 2011. Accessed January 2012.) Available from http://www.gesida.seimc.org/pcientifica/fuentes/DcyRc/gesidadcyrc2011-Documentoconsenso-TAR-adulto-verordenador.pdf.

36.

Caro-Murillo

A.M.

, Gutiérrez

, Manuel Ramos

[HIV infection in immigrants in Spain: epidemiological characteristics and clinical presentation in the CoRIS Cohort (2004–2006)]. Enferm Infecc Microbiol Clin 2009; 27: 380–388. Spanish.

37.

Pérez Cachafeiro

, Del Amo

, Iribarren

J.A.

Decrease in serial prevalence of coinfection with hepatitis C virus among HIV-infected patients in Spain, 1997–2006. Clin Infect Dis 2009; 48: 1467–1470.

38.

Hegazi

, Bailey

R.L.

, Ahadzie

, Alabi

, Peterson

Literacy, education and adherence to antiretroviral therapy in The Gambia. AIDS Care 2010; 22: 1340–1345.

39.

Collazos

, Asensi

, Carton

J.A.

, Ibarra

The influence of the patients’ educational levels on socioeconomic, clinical, immunological and virological endpoints. AIDS Care 2009; 21: 511–519.

40.

Soon

G.G.

, Min

, Struble

K.A.

Meta-analysis of gender differences in efficacy outcomes for HIV-positive subjects in randomized controlled clinical trials of antiretroviral therapy (2000–2008). AIDS Patient Care STDS 2012; 26: 444–453.

41.

Currier

, Averitt Bridge

, Hagins

Sex-based outcomes of darunavir-ritonavir therapy. Ann Intern Med 2010; 153: 349–357.

42.

Murri

, Lepri

A.C.

, Phillips

A.N.

Access to antiretroviral treatment, incidence of sustained therapy interruptions, and risk of clinical events according to sex: evidence from the I.Co.N.A. Study. J Acquir Immune Defic Syndr 2003; 34: 184–190.

43.

Squires

K.E.

, Johnson

, Yang

Comparative gender analysis of the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir at 96 weeks in the CASTLE study. J Antimicrob Chemother 2011; 66: 363–370.

44.

Barber

T.J.

, Geretti

A.M.

, Anderson

Outcomes in the first year after initiation of first-line HAART among heterosexual men and women in the UK CHIC Study. Antivir Ther 2011; 16: 805–814.

45.

Smith

C.J.

, Sabin

C.A.

, Youle

M.S.

Response to efavirenz-containing regimens in previously antiretroviral-naive HIV-positive patients: the role of gender. J Acquir Immune Defic Syndr 2007; 46: 62–67.

46.

Hermes

, Fredrick

, Pasley

, Trinh

, Martinez

, Norton

Efficacy, safety and tolerability of lopinavir/ ritonavir (LPV/r) in HIV-infected women: results of a meta-analysis of 7 prospective randomized clinical trials (RCTs) through 48 weeks. 1st International Workshop on HIV and Women. 10–11 January 2011, Washington, DC, USA. Oral abstract O_17.

47.

Kempf

M.C.

, Pisu

, Dumcheva

, Westfall

A.O.

, Kilby

J.M.

, Saag

M.S.

Gender differences in discontinuation of antiretroviral treatment regimens. J Acquir Immune Defic Syndr 2009; 52: 336–341.

48.

Taylor-Smith

, Tweya

, Harries

, Schoutene

, Jahn

Gender differences in retention and survival on antiretroviral therapy on HIV-1 infected adults in Malawi. Malawi Med J 2010; 22: 49–56.