Trends in CD4 cell count response to first-line antiretroviral treatment in HIV-positive patients from Asia,2003–2013: TREAT Asia HIV Observational Database Low Intensity Transfer

Abstract

Antiretroviral treatment (ART) guidelines have changed over the past decade, recommending earlier initiation and more tolerable regimens. The study objective was to examine the CD4 response to ART, depending on the year of ART initiation, in HIV-positive patients in the Asia-Pacific. We included HIV-positive adult patients who initiated ART between 2003 and 2013 in our regional cohort from eight urban referral centres in seven countries within Asia. We used mixed-effects linear regression models to evaluate differences in CD4 response by year of ART initiation during 36 months of follow-up, adjusted a priori for other covariates. Overall, 16,962 patients were included. Patients initiating in 2006–9 and 2010–13 had an estimated mean CD4 cell count increase of 8 and 15 cells/µl, respectively, at any given time during the 36-month follow-up, compared to those in 2003–5. The median CD4 cell count at ART initiation also increased from 96 cells/µl in 2003–5 to 173 cells/µl in 2010–13. Our results suggest that the CD4 response to ART is modestly higher for those initiating ART in more recent years. Moreover, fewer patients are presenting with lower absolute CD4 cell counts over time. This is likely to reduce their risk of opportunistic infections and future non-AIDS defining cancers.

Keywords

Asia HIV epidemiology CD4 trends immunological response antiretroviral treatment

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References

Mellors

Munoz

Giorgi

et al.

Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 1997; 126: 946–954.

Korenromp

Williams

Schmid

et al.

Clinical prognostic value of RNA viral load and CD4 cell counts during untreated HIV-1 infection – a quantitative review. PLoS One 2009; 4: e5950–e5950.

Lapadula

Chatenoud

Gori

et al.

Risk of severe non AIDS events is increased among patients unable to increase their CD4+ T-cell counts >200+/mul despite effective HAART. PLoS One 2015; 10: e0124741–e0124741.

Engsig

Zangerle

Katsarou

et al.

Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery. Clin Infect Dis 2014; 58: 1312–1321.

Bray

Gedeon

Hadi

et al.

Predictive value of CD4 cell count nadir on long-term mortality in HIV-positive patients in Uganda. HIV AIDS 2012; 4: 135–140.

Pacheco

Jarrin

Rosado

et al.

Increased risk of non-AIDS-related events in HIV subjects with persistent low CD4 counts despite cART in the CoRIS cohort. Antivir Res 2015; 117: 69–74.

Reniers

Slaymaker

Nakiyingi-Miiro

et al.

Mortality trends in the era of antiretroviral therapy: evidence from the network for analysing longitudinal population based HIV/AIDS data on Africa (ALPHA). AIDS 2014; 28: S533–S542.

Vermund

. Treatment as prevention for HIV in China. Lancet 2013; 382: 1159–1161.

van Sighem

Danner

Ghani

et al.

Mortality in patients with successful initial response to highly active antiretroviral therapy is still higher than in non-HIV-infected individuals. J Acquir Immune Defic Syndr 2005; 40: 212–218.

10.

World Health Organisation. Scaling up antiretroviral therapy in resource-limited settings. Geneva: World Health Organisation, 2002.

11.

Booth

Garcia-Diaz

Youle

et al.

Prevalence and predictors of antiretroviral drug resistance in newly diagnosed HIV-1 infection. J Antimicrob Chemother 2007; 59: 517–524.

12.

Bangsberg

Moss

. When should we delay highly active antiretroviral therapy? J Gen Intern Med 1999; 14: 446–448..

13.

Hermans

van Leth

Manabe

et al.

Earlier initiation of antiretroviral therapy, increased tuberculosis case finding and reduced mortality in a setting of improved HIV care: a retrospective cohort study. HIV Med 2012; 13: 337–344.

14.

Romley

Juday

Solomon

et al.

Early HIV treatment led to life expectancy gains valued at $80 billion for people infected in 1996–2009. Health Affairs 2014; 33: 370–377.

15.

Sterling

Chaisson

Keruly

et al.

Improved outcomes with earlier initiation of highly active antiretroviral therapy among human immunodeficiency virus-infected patients who achieve durable virologic suppression: longer follow-up of an observational cohort study. J Infect Dis 2003; 188: 1659–1665.

16.

World Health Organisation. Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV, http://apps.who.int/iris/bitstream/10665/186275/1/9789241509565_eng.pdf (2015, accessed January 2016).

17.

World Health Organisation. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. Geneva: World Health Organisation, http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf (2013, accessed October 2015).

18.

Cornell

Grimsrud

Fairall

et al.

Temporal changes in programme outcomes among adult patients initiating antiretroviral therapy across South Africa, 2002–2007. AIDS 2010; 24: 2263–2270.

19.

Krentz

Kliewer

Gill

. Changing mortality rates and causes of death for HIV-infected individuals living in Southern Alberta, Canada from 1984 to 2003. HIV Med 2005; 6: 99–106.

20.

Kee

Lee

Kim

et al.

Improvement in survival among HIV-infected individuals in the Republic of Korea: need for an early HIV diagnosis. BMC Infect Dis 2009; 9: 128–128.

21.

De La Mata

Kumarasamy

Khol

et al.

Improved survival in HIV treatment programmes in Asia. Antivir Therapy. 21: 517–527.

22.

Farahani

Price

El-Halabi

et al.

Trends and determinants of survival for over 200 000 patients on antiretroviral treatment in the Botswana National Program: 2002–2013. AIDS 2016; 30: 477–485.

23.

Smith

Sabin

Youle

et al.

Factors influencing increases in CD4 cell counts of HIV-positive persons receiving long-term highly active antiretroviral therapy. J Infect Dis 2004; 190: 1860–1868.

24.

Asfaw

Ali

Eticha

et al.

CD4 cell count trends after commencement of antiretroviral therapy among HIV-infected patients in Tigray, Northern Ethiopia: a retrospective cross-sectional study. PLoS One 2015; 10: e0122583–e0122583.

25.

Wright

Petoumenos

Boyd

et al.

Ageing and long-term CD4 cell count trends in HIV-positive patients with 5 years or more combination antiretroviral therapy experience. HIV Med 2013; 14: 208–216.

26.

Rajasuriar

Gouillou

Spelman

et al.

Clinical predictors of immune reconstitution following combination antiretroviral therapy in patients from the Australian HIV observational database. PLoS One 2011; 6: e20713–e20713.

27.

van Leth

Wit

Reiss

et al.

Differential CD4 T-cell response in HIV-1-infected patients using protease inhibitor-based or nevirapine-based highly active antiretroviral therapy. HIV Med 2004; 5: 74–81.

28.

Mocroft

Phillips

Ledergerber

et al.

Relationship between antiretrovirals used as part of a cART regimen and CD4 cell count increases in patients with suppressed viremia. AIDS 2006; 20: 1141–1150.

29.

Zhou

Kumarasamy

Ditangco

et al.

The TREAT Asia HIV observational database: baseline and retrospective data. J Acquir Immune Defic Syndr 2005; 38: 174–179.

30.

Avila

Althoff

Mugglin

et al.

Immunodeficiency at the start of combination antiretroviral therapy in low-, middle-, and high-income countries. J Acquir Immune Defic Syndr 2014; 65: E8–E16.

31.

Lesko

Cole

Zinski

et al.

A systematic review and meta-regression of temporal trends in adult CD4(+) cell count at presentation to HIV care, 1992–2011. Clin Infect Dis 2013; 57: 1027–1037.

32.

Duda

Farr

Lindegren

et al.

Characteristics and comprehensiveness of adult HIV care and treatment programmes in Asia-Pacific, sub-Saharan Africa and the Americas: results of a site assessment conducted by the International epidemiologic Databases to Evaluate AIDS (IeDEA) collaboration. J Int AIDS Soc 2014; 17: 19045–19045.

33.

Wood

Hogg

Yip

et al.

The impact of adherence on CD4 cell count responses among HIV-infected patients. J Acquir Immune Defic Syndr 2004; 35: 261–268.

34.

Lima

Harrigan

Murray

et al.

Differential impact of adherence on long-term treatment response among naive HIV-infected individuals. AIDS 2008; 22: 2371–2380.

35.

Safren

Kumarasamy

James

et al.

ART adherence, demographic variables and CD4 outcome among HIV-positive patients on antiretroviral therapy in Chennai, India. AIDS Care 2005; 17: 853–862.

36.

van Griensven

Phirum

Choun

et al.

Hepatitis B and C co-infection among HIV-infected adults while on antiretroviral treatment: long-term survival, CD4 cell count recovery and antiretroviral toxicity in Cambodia. PLoS One 2014; 9: e88552–e88552.

37.

Maskew

Brennan

Westreich

et al.

Gender differences in mortality and CD4 count response among virally suppressed HIV-positive patients. J Women’s Health 2013; 22: 113–120.

38.

Hughes

Sterne

JAC

Walsh

et al.

Long-term trends in CD4 cell counts and impact of viral failure in individuals starting antiretroviral therapy: UK Collaborative HIV Cohort (CHIC) study. HIV Med 2011; 12: 583–593.

39.

Damtie

Yismaw

Woldeyohannes

et al.

Common opportunistic infections and their CD4 cell correlates among HIV-infected patients attending at antiretroviral therapy clinic of Gondar University Hospital, Northwest Ethiopia. BMC Res Notes 2013; 6: 534–534.

40.

Franzetti

Adorni

Parravicini

et al.

Trends and predictors of non-AIDS-defining cancers in men and women with HIV infection: a single-institution retrospective study before and after the introduction of HAART. J Acquir Immune Defic Syndr 2013; 62: 414–420.

41.

Calabresi

Ferraresi

Festa

et al.

Incidence of AIDS-defining cancers and virus-related and non-virus-related non-AIDS-defining cancers among HIV-infected patients compared with the general population in a large health district of Northern Italy, 1999–2009. HIV Med 2013; 14: 481–490.

42.

Lewden

Chene

Morlat

et al.

HIV-infected adults with a CD4 cell count greater than 500 cells/mm³ on long-term combination antiretroviral therapy reach same mortality rates as the general population. J Acquir Immune Defic Syndr 2007; 46: 72–77.

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