Sex differences in antiretroviral treatment outcomes among HIV-infected adults in an urban Tanzanian setting

Objective:To determine the relationship between sex and antiretroviral therapy (ART) outcomes in an urban Tanzanian setting. Design:Longitudinal analysis of a cohort of HIV-infected adult men and women on ART enrolled at the Management and Development for Health (MDH)-President's Emergency Plan For AIDS Relief (PEPFAR) HIV care and treatment program in Dar es Salaam, Tanzania. Methods:Clinical and immunologic responses to ART were compared between HIV-infected men and women enrolled from November 2004 to June 2008. Cox regression analyses were used to study sex differences with regard to mortality, immunologic failure (WHO, 2006) and loss to follow-up, after adjusting for other risk factors for the outcomes. Results:Four thousand, three hundred and eighty-three (34%) men and 8459 (66%) women were analyzed. Men were significantly more immunocompromised than women at enrollment in terms of stage IV disease (27 vs. 23%, P < 0.001) and mean CD4+ cell count (123 vs. 136 cells/μl, P < 0.001). In multivariate analyses, men had a significantly higher risk of overall mortality [hazard ratio 1.19, 95% confidence interval (CI) 1.05–1.30, P < 0.001], immunologic nonresponse defined as CD4 cell count less than 100 cells/μl after at least 6 months of initiating ART (hazard ratio 1.74, 95% CI 1.44–2.11, P < 0.001) and loss to follow-up (hazard ratio 1.19, 95% CI 1.10–1.30, P < 0.001) than that in women. Associations did not change significantly when restricting analyses to the period of good adherence for all patients. Conclusion:Nonadherence to care and advanced immunodeficiency at enrollment explained only 17% of the inferior mortality in HIV-infected men in this resource-limited setting. Additional study of behavioral and biologic factors that may adversely impact treatment outcomes in men is needed to reduce these sex disparities.

[1]  I. Waldron,et al.  Recent trends in sex mortality ratios for adults in developed countries. , 1993, Social science & medicine.

[2]  P Flandre,et al.  Estimating the proportion of treatment effect explained by a surrogate marker. , 1999, Statistics in Medicine.

[3]  Julio S. G. Montaner,et al.  Rates of disease progression by baseline CD4 cell count and viral load after initiating triple-drug therapy. , 2001, JAMA.

[4]  C. Poole,et al.  Gender Difference in HIV RNA Levels: A Meta‐Analysis of Published Studies , 2002, Journal of acquired immune deficiency syndromes.

[5]  C. Fletcher,et al.  Antiviral dynamics and sex differences of zidovudine and lamivudine triphosphate concentrations in HIV-infected individuals , 2003, AIDS.

[6]  J. Slim,et al.  Women have a greater immunological response to effective virological HIV-1 therapy. , 2003, AIDS.

[7]  Anne M Johnson,et al.  Virologic, Immunologic, and Clinical Response to Highly Active Antiretroviral Therapy: the Gender Issue Revisited , 2003, Journal of acquired immune deficiency syndromes.

[8]  J. del Romero,et al.  Gender differences in progression to AIDS and death from HIV seroconversion in a cohort of injecting dug users from 1986 to 2001 , 2004, Journal of Epidemiology and Community Health.

[9]  R. Johann-Liang,et al.  Hepatotoxicity associated with nevirapine use. , 2004, Journal of acquired immune deficiency syndromes.

[10]  N. Hessol,et al.  Sex and the course of HIV infection in the pre- and highly active antiretroviral therapy eras , 2005, AIDS.

[11]  E. Nicastri,et al.  Gender differences in clinical progression of HIV-1-infected individuals during long-term highly active antiretroviral therapy , 2005, AIDS.

[12]  J. Sterne,et al.  Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries , 2006, The Lancet.

[13]  B. Stilwell,et al.  Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach. 2006 revision. , 2006 .

[14]  P. Kaleebu,et al.  Virological response to a triple nucleoside/nucleotide analogue regimen over 48 weeks in HIV-1-infected adults in Africa , 2006, AIDS.

[15]  Saad B Omer,et al.  Adherence to Highly Active Antiretroviral Therapy Assessed by Pharmacy Claims Predicts Survival in HIV-Infected South African Adults , 2006, Journal of acquired immune deficiency syndromes.

[16]  L. Myer,et al.  Determinants of mortality and nondeath losses from an antiretroviral treatment service in South Africa: implications for program evaluation. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  J. Hitti,et al.  Antiretroviral pharmacokinetic profile: a review of sex differences. , 2007, Gender medicine.

[18]  C. Rouzioux,et al.  Positive outcomes of HAART at 24 months in HIV-infected patients in Cambodia , 2007, AIDS.

[19]  C. Sabin,et al.  Response to Efavirenz-Containing Regimens in Previously Antiretroviral-Naive HIV-Positive Patients: The Role of Gender , 2007, Journal of acquired immune deficiency syndromes.

[20]  J. Carton,et al.  Sex differences in the clinical, immunological and virological parameters of HIV-infected patients treated with HAART , 2007, AIDS.

[21]  P. Narciso,et al.  Sex issues in HIV-1-infected persons during highly active antiretroviral therapy: a systematic review. , 2007, The Journal of antimicrobial chemotherapy.

[22]  F. Dabis,et al.  Rapid scaling-up of antiretroviral therapy in 10 000 adults in Côte d'Ivoire: 2-year outcomes and determinants , 2008, AIDS.

[23]  M. Hill,et al.  Determinants of target organ damage in black hypertensive patients attending primary health care services in Cape Town: the Hi-Hi study. , 2008, American journal of hypertension.

[24]  A. Harries,et al.  Increased mortality of male adults with AIDS related to poor compliance to antiretroviral therapy in Malawi , 2008, Tropical medicine & international health : TM & IH.

[25]  N. Low,et al.  Gender and the use of antiretroviral treatment in resource-constrained settings: findings from a multicenter collaboration. , 2008, Journal of women's health.

[26]  Aniset Kamanga,et al.  Predictors of Adherence to Antiretroviral Therapy in Rural Zambia , 2008, Journal of acquired immune deficiency syndromes.

[27]  Avis J. Thomas,et al.  Ethnicity, Race, and Gender: Differences in Serious Adverse Events Among Participants in an Antiretroviral Initiation Trial: Results of CPCRA 058 (FIRST Study) , 2008, Journal of acquired immune deficiency syndromes.

[28]  R. Geskus,et al.  Gender differences in HIV progression to AIDS and death in industrialized countries: slower disease progression following HIV seroconversion in women. , 2008, American journal of epidemiology.

[29]  T. Flanigan,et al.  Gender-based differences in treatment and outcome among HIV patients in South India. , 2008, Journal of women's health.

[30]  T. Quinn,et al.  Failure of immunologic criteria to appropriately identify antiretroviral treatment failure in Uganda , 2009, AIDS.

[31]  S. Cha,et al.  Youth, unemployment, and male gender predict mortality in AIDS patients started on HAART in Nigeria , 2009, AIDS care.

[32]  D. Spiegelman,et al.  The International Journal of Biostatistics The Comparison of Alternative Smoothing Methods for Fitting Non-Linear Exposure-Response Relationships with Cox Models in a Simulation Study , 2011 .

[33]  L. D. Saunders,et al.  Gender differences in antiretroviral treatment outcomes of HIV patients in rural Uganda , 2010, AIDS care.

[34]  E. Muls,et al.  Mortality of young patients with diabetes in Kinshasa, DR Congo , 2010, Diabetic medicine : a journal of the British Diabetic Association.

[35]  A. Alibhai,et al.  Gender-related mortality for HIV-infected patients on highly active antiretroviral therapy (HAART) in rural Uganda , 2010, International journal of women's health.