Table 1.
Considerations by Sex of Modern Antiretroviral Therapy Use Among Women and Men With HIV by Antiretroviral Agent/Class and At-Risk Comorbid Condition
| ART Agent or Class | Bone Disease | Cardiovascular Risk | Metabolic Dysfunction | Neuropsychiatric Effects |
|---|---|---|---|---|
| Nucleoside reverse transcriptase inhibitors | ||||
| Abacavir | Switching from TDF to ABC led to improved femoral neck BMD at 48wk, though no significant difference compared with those maintained on TDF and data not sex-stratified [129] | Association of ABC with MI remains unclear and controversial [130], though sex not associated with increased MI risk [131]; among women, ABC use was associated with higher triglycerides vs no use [132] | ABC use has not been associated with significant metabolic effects among PWH | Neuropsychiatric sequelae of ABC use are limited to case reports of mania occurring among men, though headache and mood alterations may be earlier indicators [133] |
| TDFa | Among women vs men, TDF exposure was associated with femoral neck BMD loss of –0.0032 vs –0.0026g/cm2 and lumbar spine BMD loss of –0.0031 vs –0.0031g/cm2 over median 4.6 y [134] | TDF has been noted to have a favorable effect on lipids [135]; among women, self-reported use of TDF was associated with lower triglyceride values (129 vs 147mg/dL, P=.009 for users vs nonusers) [132] | Women vs men gained 3.2 vs 3.0kg 48 weeks after DTG-based ART initiation plus TDF [136] | There are limited data on the neuropsychiatric effects of tenofovir drugs, and overall TDF and TAF are considered well-tolerated in terms of possible CNS effects |
| TAFb | Switching from TDF- to TAF-based ART improved bone outcomes among virologically suppressed PWH, but data not sex-stratified [137]; providers may consider weighing the overall risk of accelerated BMD loss among women vs greater TAF-associated weight gain for women | Levels of triglycerides and HDL and LDL cholesterol were higher among patients receiving TAF than TDF; however, the total cholesterol-to-LDL ratio did not differ [138]; sex-stratified data not available | Women vs men gained 6.4 vs 4.7kg 48 weeks after DTG-based ART initiation plus TAF [136]; among women switching to TAF (without INSTI), the observed increase in weight and BMI (+0.4kg and +0.2kg/m2, respectively) were significant for those with preswitch BMI <30kg/m2 (but not ≥30kg/m2)[139] | |
| Nonnucleoside reverse transcriptase inhibitors | ||||
| Efavirenz | There are limited data on the effects of NNRTI agents on BMD, and overall NNRTI-related bone effects are considered minimal | EFV use has been associated with better HDL cholesterol and less deleterious triglyceride responses among women than men [132] | Women are more likely than men to experience lipohypertrophy, and in particular truncal obesity, associated with NNRTI/EFV use, whereas men vs women are more likely to experience lipoatrophy [140]; body fat distribution changes appear similar for those on EFV- vs RPV-based ART [141] | CNS symptoms are more commonly observed with EFV than RPV [142]; higher incidence of abnormal dreams/nightmares among men vs women, but no sex differences in headache, somnolence, insomnia [143] |
| Rilpivirine | RPV has been shown to have less effect on lipids than EFV [144]; switching from PI/ritonavir to RPV was associated with improved lipid profiles and 10-year Framingham score [145]; sex-stratified data not available | |||
| Doravirine | More favorable lipid effects among those on DOR vs EFV; sex differences not apparent [146] | Mean 96-wk weight gain higher among women vs men (3.2 vs 2.2kg); sex not associated with ≥10% weight gain or BMI class increase in multivariate analyses [147] | Fewer neuropsychiatric effects experienced on DOR than EFV; sex differences not apparent [146] | |
| Protease inhibitors | ||||
| Atazanavir (boosted) | Among women, osteoporosis risk was increased for use of PI + no TDF (HR, 5.9 [95% CI, 1.2–27.6]) and for PI + TDF (HR, 6.9 [95% CI, 1.4–34.4]) compared with no PI + no TDF; however, the corresponding values among men were 1.8 (95% CI, .9–3.4) and 1.2 (95% CI, .6–2.6), respectively [30] | ATV appears protective against ischemic CVD; sex not associated with ATV-associated effect [148, 149] | The treatment difference for change in WC for ATV/ritonavir vs RAL was greater for women than for men (differential mean change of –3.28cm [95% CI, –5.65 to .92], P=.0065) [150] | Little evidence of specific CNS toxicity associated with PI use, although there may be a risk of peripheral neuropathy with ATV [151]; sex-stratified data not available |
| Darunavir (boosted) | 9.6% of men compared with 3.7% of women experienced grade 2–4 adverse lipid effects after DRV/cobicistat initiation [152] | The treatment difference for change in WC for DRV/ritonavir vs RAL was greater for women than for men (differential mean change of –2.01cm [95% CI, -4.32 to .31], P=.0901) [150] | 7.4% of women compared with 3.1% of men experienced grade 2–4 adverse CNS effects after DRV/cobicistat initiation [152] | |
| Integrase strand transfer inhibitors | ||||
| Dolutegravir | Switching from TDF/FTC + NNRTI to ABC/3TC/DTG resulted in improved total hip and lumbar spine BMD among women (mean adjusted increase of 1% and 3%, respectively) [153] | Sex-adjusted DTG-associated weight gain negatively impacts lipids and fasting glucose levels [154]; among women over median of 2 years, unfavorable changes in HbA1c and systolic and diastolic BP observed [155] | Women but not men experienced significant weight gain after switch to DTG [154] from non-INSTI ART; among women over mean 2 years of follow-up, weight increased by 2.1kg, BMI by 0.8kg/m2, and WC by 2.0cm [156] | Women more likely than men to discontinue DTG due to neuropsychiatric adverse effects (HR, 2.64 [95% CI, 1.23–5.65]) [157] |
| Bictegravir | BIC-associated changes in BMD appear similar to DTG [158]; sex-stratified data not available | BIC appears to be lipid-neutral and even have favorable lipid effect if switched from boosted-PI regimen [159]; sex-stratified data not available | Weight gain associated with BIC exposure among treatment-naive PWH appears similar to DTG [160]; sex-stratified data not available | Head-to-head trial of ABC/3TC/DTG vs TAF/FTC/BIC showed a similar distribution of CNS and psychiatric adverse events [159]; sex-stratified data not available |
| Cabotegravir | Research priority area: phase 3 clinical trial data (FLAIR, ATLAS, ATLAS-2M) not reported as sex-stratified | |||
Abbreviations: 3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; ATLAS, antiretroviral therapy as long acting suppression; ATLAS-2M, antiretroviral therapy as long acting suppression every 2 months; ATV, atazanavir; BIC, bictegravir; BMI, body mass index; BMD, bone mineral density; BP, blood pressure; CI, confidence interval; CNS, central nervous system; CVD, cardiovascular disease; DOR, doravirine; DRV, darunavir; DTG, dolutegravir; EFV, efavirenz; FLAIR, first long-acting injectable regimen; FTC, emtricitabine; HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; HR, hazard ratio; INSTI, integrase strand transfer inhibitor; LDL, low-density lipoprotein; MI, myocardial infarction; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; PWH, persons with HIV; RAL, raltegravir; RPV, rilpivirine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; WC, waist circumference.
Can be used safely in patients with normal kidney function (estimated glomerular filtration rate [eGFR] ≥60min/mL/1.73 m2).
Can be used safely in patients with moderately reduced kidney function (eGFR ≥30min/mL/1.73 m2) but should be avoided in those with severely reduced kidney function not on hemodialysis; drug interactions possible with rifamycins and certain anticonvulsants.