Brief Report

Sex Differences in Outcomes for Individuals Presenting for Third-Line Antiretroviral Therapy

Catherine Godfrey, MD, FRACP; Michael D. Hughes, PhD; Justin Ritz, MS; Lara Coelho, MD; Robert Gross, MD, MSCE; Robert Salata, MD; Rosie Mngqibisa, MB ChB; Carole L. Wallis, PhD, MSc; Makanga. E. Mumbi, MD; Mitch Matoga, MD; Selvamuthu Poongulali, MBChB; Marije Van Schalkwyk, MD; Evelyn Hogg, BA; Courtney V. Fletcher, PharmD; Beatriz Grinsztejn, MD, PhD; Ann C. Collier, MD

Disclosures

J Acquir Immune Defic Syndr. 2020;84(2):203-207. 

In This Article

Results

The demographics of the A5288 participants are presented elsewhere.[1] Women represented 47% of the total study population (258/545). They were more likely than men to have received nevirapine(NVP) (70% vs. 60%, P = 0.003) largely driven by the fact that more women than men had previous NVP use in cohort A (69% vs. 47%). Women were less likely to have received efavirenz (49% vs. 64%, P < 0.001) before study entry. More women were assigned to cohort A (62% vs. 44%) and fewer to cohorts BCD (38% vs. 56%) (P < 0.001). Women were slightly younger than men (median 39 vs. 43 years, P < 0.001) with slightly lower weight (median 56.3 vs. 59.0 kg, P = 0.020), but had similar CD4 counts (median 172 vs. 179 cells/mm3, P = 0.84) and HIV-1 RNA levels (median 4.3 vs. 4.5 log10 copies/mL, P = 0.38).

In the analyses adjusted for cohort group, fewer women achieved virological suppression at week 48 {odds ratio [OR] [95% confidence interval (CI)] 0.64 [0.43 to 0.96], P = 0.030}, and more women than men experienced confirmed VF during the median follow-up of 72 weeks (hazard ratio [HR] (95% CI) 1.48 (1.08 to 2.03), P = 0.014) (Table 1). In the multivariable analyses, these associations were attenuated {[HIV-1 RNA ≤200 copies/mL at week 48: aOR (95% CI) 0.87 (0.54 to 1.39), P = 0.56]; [VF: aHR (95% CI) 1.37 (0.97 to 1.93), P = 0.075]}.

Table 1 also displays differences in clinical outcomes. Women were more likely than men to have grade ≥3 signs and symptoms (20% vs. 9%), an effect that was seen in both cohort A and cohorts BCD (HR (95% CI) 1.87 (1.17 to 2.99), P = 0.009). This effect persisted in the multivariable analysis [aHR (95% CI) 1.67 (1.01 to 2.74), P = 0.044]. Sex differences in grade 3+ s/s in cohort A were seen among participants on LPV (26% for women vs. 16% for men) and ATV (19% for women vs. 12% for men). There were no significant differences by sex in multivariable analyses of serious adverse events, grade ≥3 diagnoses, or grade ≥3 laboratory abnormalities.

Participants experiencing a grade ≥3 sign/symptom during the first 48 weeks of follow-up had a lower probability of achieving virological suppression at week 48 regardless of cohort group. Specifically, among the 51 participants who experienced a grade ≥3 sign/symptom during the first 48 weeks of follow-up, only 15 (29%) achieved HIV-1 RNA ≤200 c/mL at week 48, whereas among the 494 participants who did not have a grade ≥3 sign/symptom during this time, 334 (68%) achieved suppression ≤200 c/mL at week 48 (P < 0.001). This association was seen in both women (15% vs. 44%) and men (25% vs. 51%) in cohort A and in both women (50% vs. 86%) and men (80% vs. 90%) in cohorts BCD. Experiencing a grade ≥3 sign/symptom, however, only partially explained the sex difference in virological suppression: The OR for sex moved toward 1.00 changing from 0.64 to 0.69 with adjustment for grade ≥3 sign/symptom (and the adjusted OR shown in Table 1 moved from 0.87 to 0.93).

Table 2 displays a descriptive summary of resistance outcomes. The proportion of men and women who experienced VF with mutations was similar in both cohort groups: 18% of women experienced VF in cohort A with a new resistance associated mutation (vs. 16% of men), whereas 2% of women in cohorts BCD had VF with a new resistance mutation (vs. 4% of the men). The difference between sexes in the overall VF rate therefore primarily reflected the fact that women were more likely than men to have VF without a new resistance mutation (38% of women vs. 25% of men in cohort A; 6% of women vs. 3% of men in cohorts BCD).

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