November 29, 2013
Evaluation of differences between human immunodeficiency virus (HIV)-infected men and women in antiretroviral therapy (ART) enrollment characteristics and outcomes might identify opportunities to improve ART program patient outcomes and prevention impact. During September 2008 - February 2012, retrospective cohort studies to estimate attrition of enrollees (i.e., from death, stopping ART, or loss to follow-up) at 6-month intervals after ART initiation were completed among samples of adult men and women (defined as aged ≥15 years or aged ≥18 years) who initiated ART during 2004-2010 in six African countries: Côte d'Ivoire in western Africa; Swaziland, Mozambique, and Zambia in southern Africa; and Uganda and Tanzania in eastern Africa. Records for 13,175 ART enrollees were analyzed; sample sizes among the six countries ranged from 1,457 to 3,682. In each country, women comprised 61%-67% of ART enrollees. Median CD4 count range was 119-141 cells/µL for men and 137-161 cells/µL for women. Compared with women, a greater percentage of men initiated ART who had World Health Organization (WHO) HIV stage IV disease. In cohorts from western Africa and southern Africa, the risk for attrition was 15%-26% lower among women compared with men in multivariable analysis. However, in eastern Africa, differences between men and women in risk for attrition were not statistically significant. Research to identify country-specific causes for increased attrition and delayed initiation of care among men could identify strategies to improve ART program outcomes among men, which might contribute to prevention of new HIV infections in female partners.
In each of the six countries, a representative sample of ART facilities was selected. To keep the studies feasible, small facilities were excluded from the sample frames of countries with >100 ART facilities at the time of sampling. Therefore, in Côte d'Ivoire and Mozambique, facilities that had enrolled <50 adults on ART were excluded, whereas in Zambia, Uganda, and Tanzania, facilities that had enrolled <300 adults on ART were excluded (Table 1).
From the eligible number of facilities in Côte d'Ivoire (78), Swaziland (31), and Mozambique (94), totals of 34, 16, and 30 study facilities, respectively, were randomly selected using probability-proportional-to-size sampling (Table 1). From the eligible number of facilities in Zambia (129), Uganda (114), and Tanzania (85), six study facilities were purposefully (nonrandomly) selected in each country to represent different types of ART facilities.
At each selected facility, a sample frame of study-eligible ART patients was created, and simple random sampling used to select the desired sample size of patient medical records. Eligibility criteria included having started ART during 2004-2010 and ≥6 months before data abstraction. Data were abstracted by trained study personnel from ART medical records onto standardized abstraction forms.
Attrition was the primary outcome of interest. A patient was considered lost to attrition if the record showed 1) the patient had died, 2) the patient had stopped ART because of a personal or clinician decision, or 3) the patient had not attended the facility in the 90 days preceding data abstraction for either medication refill or a clinician visit, in which case the patient was considered lost to follow-up.
Variables routinely collected on Ministry of Health medical records at ART initiation including sex, age, CD4 count, WHO HIV disease stage, and ART regimen, were entered into standardized abstraction forms. Data were analyzed using statistical software, and study design was controlled for during analysis. Data for Côte d'Ivoire, Swaziland, and Mozambique were weighted to account for the probability-proportional-to-size sampling.
To estimate the effect of sex on attrition, Cox proportional hazards regression models were used to estimate unadjusted and adjusted hazard ratios, 95% confidence intervals, and p-values. Multivariate models included only cases with complete data for sex, age, CD4 count, WHO HIV disease stage, and ART regimen. The proportional hazards assumption was assessed using visual methods and the Grambsch and Therneu test.1 For all countries, a shared frailty model was used to account for intrafacility correlation. Chi-square tests were used to compare distributions of categorical variables, and t-tests were used to compare distributions of continuous variables between men and women. Attrition at 6-month intervals after ART initiation was analyzed using the Kaplan-Meier product-limit estimate of the survivor function.
The sample sizes in the six countries ranged from 1,457 to 3,682, with a total of 13,175 records analyzed (Table 2). In each country, 61%-67% of ART enrollees were women. In each country, men were significantly older than women at ART initiation. Median age range for men was 37-40 years, and for women was 32-35 years.
Compared with women, median CD4 count at ART initiation was significantly lower among men in Côte d'Ivoire (119/µL compared with 155/µL), Swaziland (121/µL compared with 161/µL), and Uganda (128/µL compared with 144/µL). Median CD4 count was lower for men compared with women in Mozambique, Zambia, and Tanzania, although these differences were not statistically significant (p>0.05).
In all countries, men initiated ART at a more advanced WHO disease stage (Table 2). For example, a higher proportion of men than women initiated ART at WHO stage IV disease in Côte d'Ivoire (26% compared with 21%), Swaziland (18% compared with 10%), Mozambique (20% compared with 13%), Zambia (11% compared with 9%), Uganda (16% compared with 10%), and Tanzania (30% compared with 27%).
For both men and women across all six countries, nevirapine-containing first-line regimens were more common than efavirenz-containing or protease inhibitor-containing regimens, or triple nucleoside reverse transcriptase inhibitor regimens (Table 2). The distribution of first-line ART regimen choices for men differed from choices for women in all countries, with women more likely to be prescribed nevirapine-containing regimens than men (Table 2).
In all countries, point estimates for attrition during the first 4.5 years of ART were lower for women than men (Table 3). This difference was statistically significant in countries in western and southern Africa, where women had 21%-27% lower rates of attrition in unadjusted analysis and 15%-26% lower rates of attrition in adjusted analysis (Table 3). In Uganda and Tanzania, women had 7%-18% lower rates of attrition in unadjusted analysis and 11%-12% lower rates of attrition in adjusted analysis, although the associations between sex and attrition rates were not statistically significant in these two countries.
Reported by: Virginie Ettiègne-Traoré, M.D., Moise Zanga Tuho, M.D., Ministry of Health; Fayama Mohamed, Ph.D., Directorate General of Budget and Finance, Côte d'Ivoire. Charles Azih, M.D., Ministry of Health, Swaziland. Francisco Mbofana, M.D., National Institute of Health, Mozambique. Modest Mulenga, M.D., Tropical Diseases Research Center, Zambia. Fred Wabwire-Mangen, Ph.D., The Infectious Diseases Institute, Makerere Univ College of Health Sciences, Uganda. Gideon Kwesigabo, Ph.D., Muhimbili Univ of Health and Allied Sciences, Tanzania. Joseph Essombo, M.D., Elizabeth Glaser Pediatric AIDS Foundation, Côte d'Ivoire. Harrison Kamiru, Dr.P.H., Harriet Nuwagaba-Biribonwoha, M.D., International Center for AIDS Care and Treatment Programs-Columbia Univ, Swaziland. Kwasi Torpey, Ph.D., FHI 360, Zambia. Eric Van Praag, M.D., FHI 360, Tanzania. Ya Diul Mukadi, M.D., FHI 360, Haiti. Olivier Koole, M.D., Joris Menten, MSc, Robert Colebunders, Ph.D., Institute of Tropical Medicine, Dept of Clinical Sciences, Belgium. Lisa J. Nelson, M.D., Dept of HIV/AIDS, World Health Organization, Switzerland. Georgette Adjorlolo-Johnson, Ph.D., Elizabeth Glaser Pediatric AIDS Foundation, California. Julie Denison, Ph.D., Sharon Tsui, M.P.H., Social and Behavioral Health Sciences, FHI 360, Washington, DC. Carol Dukes Hamilton, M.D., Timothy Mastro, M.D., Global Health, Population & Nutrition, FHI 360, Durham, North Carolina. David Bangsberg, M.D., Massachusetts General Hospital. Kunomboa A. Ekra, M.D., Joseph S. Kouakou, M.D., Center for Global Health, CDC-Côte d'Ivoire. Peter Ehrenkranz, M.D., Trong Ao, Sc.D., Center for Global Health, CDC-Swaziland. Charity Alfredo, M.D., Kebba Jobarteh, M.D., Center for Global Health, CDC-Mozambique. Seymour Williams, M.D., Center for Global Health, CDC-South Africa. Ray W. Shiraishi, Ph.D., Andrew Baughman, Ph.D., Simon Agolory, M.D., George Bicego, Ph.D., Thomas Spira, M.D., Aaron Zee, M.P.H., Jonathan Kaplan, M.D., Tedd V. Ellerbrock, M.D., Andrew F. Auld, M.B.Ch.B., Div of Global HIV/AIDS, Center for Global Health, CDC. Corresponding contributor: Andrew F. Auld, CDC, 404-639-8997, firstname.lastname@example.org.
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