Combined Effect of Sex and Age in Response to Antiretroviral Therapy in HIV-Infected Patients

Abstract

Background

Gender-specific data on the management of HIV infection are scarce. Further, an increase in the proportion of new HIV diagnoses in older persons has been observed. Using data from the CoRIS cohort, we compared immunovirological responses and survival in HIV-infected men and women who started their first combination anti-retroviral therapy (cART) when aged </≥50 years.

Methods

We used multivariable logistic, linear and Cox regression, adjusting for potential confounders and including an interaction between age and sex, to assess differences in immunovirological responses and mortality, respectively.

Results

At 96 weeks, among subjects <50 years, women were less likely than men to achieve virological response (VR; adjusted OR [aOR] 0.77, 95% CI 0.60, 0.99) and among women, older individuals were more likely to achieve VR than the younger ones (aOR 1.96; 95% CI 1.15, 3.34). Initiating cART at ≥50 years was associated with lower increases in CD4⁺ T-cell count both in men (-65.8; 95% CI -91.3, -40.3) and women (-37.7; 95% CI -79.7, 4.4) and women showed higher increases than men in both subjects aged <50 (21.8; 95% CI -1.9, 45.5) and ≥50 years at cART initiation (49.9; 95% CI 19.9, 79.9). A higher risk of death in men ≥50 was observed (adjusted hazard ratio [aHR] 2.69; 95% CI 1.73, 4.21), but not in women (aHR 1.49; 95% CI 0.70, 1.14). Women experienced lower mortality than men <50 (0.66; 95% CI 0.41, 1.07) and in those ≥50 (0.37; 95% CI 0.14, 0.93).

Conclusions

Sex and age at cART initiation have a noticeable association with both virological and immunological responses and mortality. Age ≥50 is associated with poorer immunological response and higher mortality but this effect is less pronounced in women than in men.

References

Lohse

, Hansen

A.B.

, Pedersen

Survival of persons with and without HIV infection in Denmark, 1995–2005.

Ann Intern Med 2007; 146: 87–95.

Porter

, Babiker

, Bhaskaran

Determinants of survival following HIV-1 seroconversion after the introduction of HAART.

Lancet 2003; 362: 1267–1274.

Deeks

S.G.

, Lewin

S.R.

, Havlir

D.V.

The end of AIDS: HIV infection as a chronic disease.

Lancet 2013; 382: 1525–1533.

Brooks

J.T.

, Buchacz

, Gebo

K.A.

, Mermin

HIV infection and older Americans: the public health perspective.

Am J Public Health 2012; 102: 1516–1526.

High

K.P.

, Brennan-Ing

, Clifford

D.B.

HIV and aging: state of knowledge and areas of critical need for research. A report to the NIH Office of AIDS Research by the HIV and Aging Working Group.

J Acquir Immune Defic Syndr 2012; 60 Suppl 1: S1–S18.

Smit

, Brinkman

, Geerlings

Future challenges for clinical care of an ageing population infected with HIV: a modelling study.

Lancet Infect Dis 2015; 15: 810–818.

Haberl

, Johnson

, Dominguez

, Miralles

, Monforte

, Anderson

The need for data on women living with HIV in Europe.

Antivir Ther 2013; 18 Suppl 2: 1–10.

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.

Kojic

E.M.

, Wang

C.C.

, Cu-Uvin

HIV and menopause: a review.

J Womens Health (Larchmt) 2007; 16: 1402–1411.

10.

Sobrino-Vegas

, Gutierrez

, 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.

11.

Copenhagen HIV programme (CHIP) home page. (Accessed 5 December 2016.) Available from http://www.cphiv.dk/Portals/0/files/Code%20Protocol%202.3.pdf.

12.

Blanco

J.R.

, Jarrin

, Vallejo

Definition of advanced age in HIV infection: looking for an age cut-off.

AIDS Res Hum Retroviruses 2012; 28: 1000–1006.

13.

de Pommerol

, Hessamfar

, Lawson-Ayayi

Menopause and HIV infection: age at onset and associated factors, ANRS CO3 Aquitaine cohort.

Int J STD AIDS 2011; 22: 67–72.

14.

Fantry

L.E.

, Zhan

, Taylor

G.H.

, Sill

A.M.

, Flaws

J.A.

Age of menopause and menopausal symptoms in HIV-infected women.

AIDS Patient Care STDS 2005; 19: 703–711.

15.

Ferreira

C.E.

, Pinto-Neto

A.M.

, Conde

D.M.

, Costa-Paiva

, Morais

S.S.

, Magalhaes

Menopause symptoms in women infected with HIV: prevalence and associated factors.

Gynecol Endocrinol 2007; 23: 198–205.

16.

Schoenbaum

E.E.

, Hartel

, Lo

HIV infection, drug use, and onset of natural menopause.

Clin Infect Dis 2005; 41: 1517–1524.

17.

Patterson

, Napravnik

, Eron

, Keruly

, Moore

Effects of age and sex on immunological and virological responses to initial highly active antiretroviral therapy.

HIV Med 2007; 8: 406–410.

18.

Althoff

K.N.

, Justice

A.C.

, Gange

S.J.

Virologic and immunologic response to HAART, by age and regimen class.

AIDS 2010; 24: 2469–2479.

19.

Grabar

, Kousignian

, Sobel

Immunologic and clinical responses to highly active antiretroviral therapy over 50 years of age. Results from the French Hospital Database on HIV.

AIDS 2004; 18: 2029–2038.

20.

Greenbaum

A.H.

, Wilson

L.E.

, Keruly

J.C.

, Moore

R.D.

, Gebo

K.A.

Effect of age and HAART regimen on clinical response in an urban cohort of HIV-infected individuals.

AIDS 2008; 22: 2331–2339.

21.

Sabin

C.A.

, Smith

C.J.

, d'Arminio

M.A.

Response to combination antiretroviral therapy: variation by age.

AIDS 2008; 22: 1463–1473.

22.

Collazos

, Asensi

, Carton

J.A.

Sex differences in the clinical, immunological and virological parameters of HIV-infected patients treated with HAART.

AIDS 2007; 21: 835–843.

23.

Moore

A.L.

, Kirk

, Johnson

A.M.

Virologic, immunologic, and clinical response to highly active antiretroviral therapy: the gender issue revisited.

J Acquir Immune Defic Syndr 2003; 32: 452–461.

24.

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.

25.

Egger

, May

, Chene

Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies.

Lancet 2002; 360: 119–129.

26.

Antiretroviral Therapy Cohort Collaboration (ART-CC).

Sex differences in overall and cause-specific mortality among HIV-infected adults on antiretroviral therapy in Europe, Canada and the US.

Antivir Ther 2015; 20: 21–28.

27.

Abioye

A.I.

, Soipe

A.I.

, Salako

A.A.

Are there differences in disease progression and mortality among male and female HIV patients on antiretroviral therapy? A meta-analysis of observational cohorts.

AIDS Care 2015; 27: 1468–1486.

28.

Patterson

K.B.

, Cohn

S.E.

, Uyanik

, Hughes

, Smurzynski

, Eron

J.J.

Treatment responses in antiretroviral treatment-naive premenopausal and postmenopausal HIV-1-infected women: an analysis from AIDS Clinical Trials Group Studies.

Clin Infect Dis 2009; 49: 473–476.

29.

Calvet

G.A.

, Velasque

, Luz

P.M.

Absence of effect of menopause status at initiation of first-line antiretroviral therapy on immunologic or virologic responses: a cohort study from Rio de Janeiro, Brazil.

PLoS One 2014; 9: e89299.

30.

Giglio

, Imro

M.A.

, Filaci

Immune cell circulating subsets are affected by gonadal function.

Life Sci 1994; 54: 1305–1312.

31.

Safadi

F.F.

, Dissanayake

I.R.

, Goodman

G.G.

Influence of estrogen deficiency and replacement on T-cell populations in rat lymphoid tissues and organs.

Endocrine 2000; 12: 81–88.

32.

Asin

S.N.

, Heimberg

A.M.

, Eszterhas

S.K.

, Rollenhagen

, Howell

A.L.

Estradiol and progesterone regulate HIV type 1 replication in peripheral blood cells.

AIDS Res Hum Retroviruses 2008; 24: 701–716.

33.

Katagiri

, Hayashi

, Victoriano

A.F.

, Okamoto

, Onozaki

Estrogen stimulates transcription of human immunodeficiency virus type 1 (HIV-1).

Int Immunopharmacol 2006; 6: 170–181.

34.

van Benthem

B.H.

, Vernazza

, Coutinho

R.A.

, Prins

The impact of pregnancy and menopause on CD4 lymphocyte counts in HIV-infected women.

AIDS 2002; 16: 919–924.

35.

Consensus document of GESIDA and Spanish Secretariat for the National Plan on AIDS (SPNS) regarding combined antiretroviral treatment in adults infected by the human immunodeficiency virus. (Accessed 5 December 2016.) Available from http://www.gesida-seimc.org/contenidos/guiasclinicas/2015/gesida-guiasclinicas-2015-tar.pdf.

36.

Pérez-Elías

M.J.

, Muriel

, Moreno

Relevant gender differences in epidemiological profile, exposure to first antiretroviral regimen and survival in the Spanish AIDS Research Network Cohort.

Antivir Ther 2014; 19: 375–385.