Selections From the DHHS Guidelines: Rapid Initiation, Weight Gain, and Neuropsychiatric Comorbidities

Selected Updates to the DHHS Guidelines: Rapid Initiation

Updated DHHS guidelines emphasize the importance of rapidly initiating ART after HIV diagnosis1


ART regimens recommended for rapid initiation1*

Boosted DRV with FTC or 3TC plus TAF or TDF


  • Boosted DRV has a high barrier to resistance and a low rate of treatment-emergent resistance

DTG with FTC or 3TC plus TDF or TAF


  • For those of childbearing potential trying to conceive or who are not using contraception, DTG is an Alternative rather than a Preferred option, as recommended in the Perinatal Guidelines
  • DTG/3TC is not recommended in rapid initiation



  • Clinical data and experience defining the BIC barrier to resistance are relatively limited at this time
  • Similar to DTG, individuals of childbearing potential who are trying to conceive or who are not using contraception, BIC is an Alternative rather than a Preferred option, as recommended in the Perinatal Guidelines

*A sample for genotypic testing should be sent before initiation of ART.

DRV/c is not recommended for use in pregnancy.

Prior to use of DTG, a pregnancy test is still recommended, and providers should discuss risks vs benefits of using DTG in this specific population. Updated Botswana data showed the risk of NTDs in infants exposed to DTG at conception is higher than in those infants not exposed to DTG.

Selected Updates to the DHHS Guidelines: Weight Gain


Greater weight gain has been associated with initiation of INSTI-containing regimens in ARV-naïve individuals than with boosted-PI regimens or NNRTIs1

  • The mean increase in weight associated with BIC and DTG was similar and greater than with EVG/c
  • Greater weight gain has also been observed after initiation of TAF or with a switch from TDF to TAF, especially in conjunction with INSTIs


INSTI-related weight gain appears to disproportionately affect female, Black, and Hispanic patients1

  • Black women showed the greatest increase in weight gain
  • Predictors and mechanism(s) for the weight gain are still unclear


The long-term consequences and reversibility of weight gain in ART remain unknown1

  • Regional distribution of weight gain, whether the weight gain is associated with significant cardiometabolic risk or whether it is reversible upon discontinuation of the offending agent, are questions that require further clarification

Considerations for Patients With Neuropsychiatric Comorbidities

People living with HIV are more likely than those in the general population to experience NPCs, such as anxiety, depression, and insomnia2,3

According to the DHHS guidelines1

  • The presence of NPCs is associated with poor retention in care and suboptimal ART adherence
    • For patients with inconsistent engagement in care or suboptimal adherence, a regimen with a high genetic barrier to resistance such as a boosted PI or second-generation INSTI should be considered

  • INSTI-based regimens have been associated with adverse neuropsychiatric effects in some retrospective cohort studies and case series
  • Select NNRTI-based regimens can exacerbate symptoms of NPCs and may be associated with suicidality

  • Patients on INSTI-based regimens who have pre-existing psychiatric conditions should be closely monitored

Differences in ARV-Related Weight Gain Are Supported by Real-World Evidence

Study design: real-world assessment of weight change in people with HIV-14

This retrospective, observational cohort study of adult PLWHIV who initiated INSTI- or PI-based regimens included data from the Optum® de-identified EHR database. This database includes patient-level records containing de-identified longitudinal data for 80 million US patients (≥7 million patients from each census region). The database also includes information on outpatient visits, diagnostic procedures, medications, laboratory results, hospitalizations, clinical notes, and patient outcomes, primarily sourced from integrated delivery networks.

The primary outcomes were change in weight and BMI within 12 months post-initiation of INSTI- vs PI-based regimens in  treatment-naïve male and female patients and in female patients alone. Change in weight and BMI from baseline measurement to follow-up measurement were reported as absolute change and percent change. Cohorts were balanced using propensity score matching (PSM). Multivariable models were used to compare outcomes of interest (outcomes were also determined by index BMI value (<25 kg/m2 vs ≥25 kg/m2).

Study limitations: EHRs do not necessarily indicate whether the patient received or took the medication. The first HIV diagnosis or prescription for ARV observed in the database may not correspond to the patient’s first diagnosis. Lastly, it was observed that a higher proportion of INSTI-based vs PI-based regimens included TAF (27.8% vs 2.4%), which has been associated with weight gain, especially in combination with INSTIs. Despite use of PSM analysis, the study was unable to determine the relative contribution of TAF vs INSTIs due to the small number of PI initiators whose regimen included TAF.

Mean change in weight and BMI, 
overall and by baseline BMI at 9.3 months mean follow-up4

  • Overall population results were consistent across multiple different endpoints4

Proportion of patients with a ≥5% or ≥10% increase in weight, 
overall and by baseline BMI4


  • After a mean 9.3-month follow-up, INSTI initiators had a 1.3 kg (2.9 lb) greater mean weight gain (1.8 kg [4.0 lb] vs 0.5 kg [1.1 lb]; 95% CI [0.5–2.0]) compared with PI initiators4
  • A greater proportion of INSTI initiators experienced ≥5% weight gain when compared to PI initiators (30.7% vs 26.1%; OR=1.26, 95% CI [1.01–1.56])4

BMI ≥25 kg/m2

  • A greater proportion of INSTI initiators with baseline BMI ≥25 kg/m2 experienced ≥5% weight gain when compared to PI initiators (27.1% vs 18.9%; OR=1.60, 95% CI [1.18–2.62])4

3TC=lamivudine; ART=antiretroviral therapy; ARV=antiretroviral; BIC=bictegravir; BMI=body mass index; DHHS=Department of Health and Human Services; DRV=darunavir; DRV/c=darunavir/cobicistat; DTG=dolutegravir; EHR=electronic health record; EVG/c=elvitegravir/cobicistat; FTC=emtricitabine; INSTI=integrase strand transfer inhibitor; NNRTI=non-nucleoside reverse transcriptase inhibitor; NPC=neurologic/psychiatric comorbidity; NTD=neural tube defect; PI=protease inhibitor; PLWHIV=people living with HIV; PSM=propensity score matching; TAF=tenofovir alafenamide; TDF=tenofovir disoproxil fumarate.

References: 1. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Updated December 18, 2019. Accessed June 24, 2020. 2. Lowther K, Selman L, Harding R, Higginson IJ. Experience of persistent psychological symptoms and perceived stigma among people with HIV on antiretroviral therapy (ART): a systematic review. Int J Nurs Stud. 2014;51(8):1171-1189. 3. Fettiplace A, Stainsby C, Winston A, et al. Psychiatric symptoms in patients receiving dolutegravir. J Acquir Immune Defic Syndr. 2017;74(4):423-431. 4. Chen Y-W, Hardy H, Pericone CD, Chow W. Real-world assessment of weight change in people with HIV-1 after initiating integrase strand transfer inhibitors or protease inhibitors. JHEOR. 2020;7(2):102-110.