Department Of Health And Human Services Guidelines Research Articles

New US DHHS Guidelines for Feeding of HIV Exposed Infants: Uptake, Practice Variability and Concerns

Abstract Background Approximately 5000 infants are born to mothers living with HIV annually in the US. In the past, the Center for Disease Control (CDC), American Academy of Pediatrics (AAP), and US Department of Health and Human Services (DHHS) have recommended that people living with HIV (PWH) not breast/chest feed their infants. Recent changes published in January 2023 in the “Section on Infant Feeding for Individuals Living with HIV” in the US DHHS HIV Guidelines, now include that individuals with HIV who are on antiretroviral therapy (ART) with a sustained undetectable viral load (VL) and who choose to breastfeed should be supported in this decision. We evaluated the uptake of these guidelines, and practice variability across providers who care for such mothers and infants. Methods We surveyed Pediatric Infectious Diseases Society members who practice clinically in the US, via an internal email list serve. The ten-question survey assessed uptake of the updated DHHS guidelines and respondents’ clinical practice in three key areas that are subject to interpretation in the guidelines: VL control, mixed feeding, and ART prophylaxis. We used descriptive statistics to examine guideline uptake and variability in practice. We used inductive qualitative thematic analysis to identify themes in open-ended survey responses. Results Of 915 individuals who opened the survey, 165 responded and 129 were included in the final analysis. Respondents represented 86 US clinical centers. Uptake varied: 14 respondents (10.8%) were unaware of the new guidelines, 103 (79.8%) had implemented or were planning to implement the new guidelines, and 12 (9.3%) were not planning to implement the guidelines. The table summarizes variability in pre-delivery VL suppression and mixed feeding criteria used by 117 respondents who are either planning/already implementing guidelines or who are unaware of guidelines. Areas of concern revealed by thematic analysis included insufficient data to support guidelines and lack of specific criteria for implementation. Conclusion We identified substantial heterogeneity in provider uptake and comfort with new breastfeeding guidelines among US pediatric infectious diseases practitioners, and variability in assessment of safety to breastfeed. Further research is essential to explore patient preferences, define necessary follow-up, and address provider concerns regarding insufficient data to support guidelines and lack of specific criteria for implementation.

New Strategies in Clinical Guideline Delivery: Randomized Trial of Online, Interactive Decision Support Versus Guidelines for Human Immunodeficiency Virus Treatment Selection by Trainees.

Support for clinicians in human immunodeficiency virus (HIV) medicine is critical given national HIV-provider shortages. The US Department of Health and Human Services (DHHS) guidelines are comprehensive but complex to apply for antiretroviral therapy (ART) selection. Human immunodeficiency virus antiretroviral selection support and interactive search tool (HIV-ASSIST) (www.hivassist.com) is a free tool providing ART decision support that could augment implementation of clinical practice guidelines. We conducted a randomized study of medical trainees at Johns Hopkins University, in which participants were asked to select an ART regimen for 10 HIV case scenarios through an electronic survey. Participants were randomized to receive either DHHS guidelines alone, or DHHS guidelines and HIV-ASSIST to support their decision making. ART selections were graded "appropriate" if consistent with DHHS guidelines, or concordant with regimens selected by HIV experts at 4 academic institutions. Among 118 trainees, participants randomized to receive HIV-ASSIST had a significantly higher percentage of appropriate ART selections compared to those receiving DHHS guidelines alone (percentage of appropriate responses in DHHS vs HIV-ASSIST arms: median [Q1, Q3], 40% [30%, 50%] vs 90% [80%, 100%]; P < .001). The effect was seen for all case types, but most pronounced for complex cases involving ART-experienced patients with ongoing viremia (DHHS vs HIV-ASSIST: median [Q1, Q3], 0% [0%, 33%] vs 100% [66%, 100%]). Trainees using HIV-ASSIST were significantly more likely to choose appropriate ART regimens compared to those using guidelines alone. Interactive decision support tools may be important to ensure appropriate implementation of HIV guidelines. NCT04080765.

Optimizing Pediatric Dosing Recommendations and Treatment Management of Antiretroviral Drugs Using Therapeutic Drug Monitoring Data in Children Living With HIV.

This review summarizes the current dosing recommendations for antiretroviral (ARV) drugs in the international pediatric guidelines of the World Health Organization (WHO), US Department of Health and Human Services (DHHS), and Pediatric European Network for Treatment of AIDS (PENTA), and evaluates the research that informed these approaches. We further explore the role of data generated through therapeutic drug monitoring in optimizing the dosing of ARVs in children. A PubMed search was conducted for the literature on ARV dosing published in English. In addition, the registration documentation of European Medicines Agency and the US Food and Drug Administration for currently used ARVs and studies referenced by the WHO, DHHS, and EMA guidelines were screened. Resulting publications were screened for papers containing data on the area under the concentration-time curve, trough concentration, and peak concentration. Studies with enrolled participants with a median or mean age of ≥18 years were excluded. No restriction on publishing date was applied. Pediatric ARV dosing is frequently based on data obtained from small studies and is often simplified to facilitate dosing in the context of a public health approach. Pharmacokinetic parameters of pediatric ARVs are subject to high interpatient variation and this leads to a potential risk of underdosing or overdosing when drugs are used in real life. To ensure optimal use of ARVs and validate dosing recommendations for children, it is essential to monitor ARV dosing more thoroughly with larger sample sizes and to include diverse subpopulations. Therapeutic drug monitoring data generated in children, where available and affordable, have the potential to enhance our understanding of the appropriateness of simplified pediatric dosing strategies recommended using a public health approach and to uncover suboptimal dosing or other unanticipated issues postmarketing, further facilitating the ultimate goal of optimizing pediatric ARV treatment.

Compliance with clinical guidelines and adherence to antiretroviral therapy among patients living with HIV

Objective: Evaluation of provider compliance with antiretroviral (ARV) treatment guidelines and patient adherence to ARVs is important for HIV care quality assessment; however, there are few current real-world data for guideline compliance and ARV adherence in the US. This study evaluated provider compliance with US Department of Health and Human Services (DHHS) guidelines and patient adherence to ARVs in a US population of patients with HIV.Methods: This was a retrospective claims study of adults with HIV-1 receiving ARV treatment between January 2010–December 2014. Follow-up began at first ARV treatment and ended at health plan disenrollment or study end. ARV regimens for treatment-naïve patients were categorized as “preferred/recommended”, “alternative”, or “non-preferred/recommended/alternative” according to DHHS guidelines. ARV adherence was evaluated using proportion of days covered (PDC) and medication possession ratio (MPR).Results: The analysis included 25,320 patients (84.4% male, mean age 45.3 years) and 39,071 regimens. Preferred/recommended regimens were most common during each study year, but the proportion of non-preferred/recommended/alternative regimens was substantial (15.9–20.6%). Only 53.6% of patients had optimal adherence by PDC ≥0.95, and 57.9% by MPR ≥0.95. Guideline non-compliance and sub-optimal adherence were more prevalent among female vs male patients (22.6% vs 14.8% [in 2014] and 65.9% vs 53.7%, respectively).Conclusions: Provider non-compliance with DHHS guidelines and sub-optimal ARV adherence among patients with HIV remain common in real-world practice, particularly for female patients. Healthcare providers should follow the latest clinical guidelines to ensure that patients receive recommended therapy, and address non-adherence when selecting ARV regimens.

PIN83 - HIV Treatment Guidelines and Medication Initiation Patterns in Treatment Naïve Adults, 2008-2016

The HIV antiretroviral therapy (ARV) landscape changes frequently with introduction of new treatments and newly published evidence. The Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines provides recommendations for how to treat newly-initiating patients and updates these guidelines regularly. Provider adoption of new guidelines in the real-world largely is unknown. This study examines the association between DHHS-recommendations and treatment decisions for HIV patients newly initiating ARVs. Patients with HIV-1 newly initiating ARV on a 3-drug regimen were identified from Optum administrative claims database (2008-2016). Continuous enrollment of 180 days prior to and 30 days following initiation was required. Patients with HIV-2 were excluded. A regimen was defined as 1 anchor ARV and 2 backbone ARVs, regardless of booster ARV, within 30 days of initiation. Each guideline period was the release date of the guideline through the day before the next release. The distribution of treatment regimens by guideline period are described by anchor medication, overall regimen, single-tablet regimen (STR), and guideline recommended versus not recommended. Results are stratified by type of insurance, age and gender. Analyses included 9,249 patients, 85% male and 62% aged 18-44 years at initiation (mean 41±12 years). During 2008-2016, top initial regimens were efavirenz + tenofovir DF (TDF)/emtricitabine (FTC) (36%), elvitegravir/cobicistat/TDF/FTC (12%), and rilpivirine + TDF/FTC (9%). Depending on the guideline period, 50% to 93% initiated on a guideline recommended regimen (72% overall). There was a clear shift from non-nucleoside reverse transcriptase inhibitors and protease inhibitors to integrase-strand transfer inhibitors. A larger percentage of females (32%) and Medicare Advantage enrollees (34%) initiated on non-recommended regimens versus males (27%) and commercial enrollees (27%), respectively. Most patients (67%) initiated on STRs. Providers generally follow DHHS guidelines, however, certain segments of the population are prescribed regimens prior to recommendation, and after they are no longer recommended.

Association between objectively assessed physical activity measures and longitudinal knee structural damage

Purpose: The relation between physical activity (PA) and the development of knee osteoarthritis (OA) is an important clinical and public health issue. Studies conducted thus far have shown conflicting results. This is most likely due to the small study samples, semi-quantitative assessment of PA and a lack of objective longitudinal data including intensity of PA. The purpose of the study was to describe the predictors and the longitudinal association between PA level and global knee structural progression. Methods: 864 participants [mean age = 65 (48–84), female % = 58] were included in this study who had valid PA data and right knee MRI data from 48 month and 72 month visits of the Osteoarthritis Initiative (OAI) study. Physical activity was monitored using ActiGraph GT1M uniaxial accelerometers (ActiGraph; Pensacola, FL). PA was categorized into time spent doing light, moderate, moderate to vigorous (MVPA) and vigorous activity depending on the activity counts/minute as described on the OAI website. PA intensity was further categorized into bouts of MVPA and vigorous activity as already describe don the OAI website. PA was further categorized to assess whether the participants met the weekly PA level prescribed American College of Sports Medicine (ACSM) and Department of Health and Human Services (DHHS). MRI data was scored using the modified Whole Organ MRI Score (WORMS). All multivariable analyses were adjusted for age, sex, BMI, radiographic OA and history of knee injury/surgery. Results: 1. Change in total modified WORMS – Baseline predictors Higher number of minutes spent doing light activity independently predicted significant worsening of total modified WORMS (β (per activity count) = +0.99 (+0.51, +1.48)). On the other hand higher number of minutes spent doing vigorous activity (β = −0.17 (−0.33, −0.01)) and more intense (β (per activity bout) = −0.14 (−0.26, −0.01)) PA were associated with a decrease in severity of WORMS over two years. – Longitudinal associations Neither changes in minutes spent in any of the four PA categories nor changes in intensity of PA over two years were significantly associated with total modified WORMS. 2. Changes in individual knee structures on MRI (i) Cartilage defects: – Baseline predictors More minutes spent doing light and moderate PA at baseline were independently associated with a significant worsening of cartilage defects over two years. – Longitudinal associations Increase in the number of minutes spent doing light activity over two years was associated with worsening cartilage defects, however increase in the minutes spent doing vigorous PA was associated with improvement in cartilage defects score. (ii) Bone marrow edema (BME): – Baseline predictors None of the baseline PA categories independently predicted change in BME over 2 years – Longitudinal associations Increase in minutes spent doing light activity was independently associated (β = 3.78 (1.42, 6.19)) with worsening BME over two years, however increase in vigorous activity minutes and intensity was associated with significant improvement in BME lesions. (iii) Meniscal pathologies – Baseline predictors More minutes spent doing light activity were associated with worsening meniscal tears over two whereas vigorous activity and higher intensity were associated with improvement in meniscal score. – Longitudinal associations Increase in time spent doing light to moderate activities was associated with improvement in meniscal scores but remained stable with vigorous PA (iv) Effusion – Baseline predictors Light activity at baseline was associated with significant improvement in severity of effusion whereas vigorous and more intense PA independently predicted worsening effusion grade. Longitudinal associations Increasing time spent doing more vigorous PA was associated with progressively worsening knee effusion. A similar trend was observed with increasing intensity of PA. Increase in PA level from baseline to meet ACSM and DHHS guidelines was generally associated with improvement in knee structural pathology grades. Conclusions: Increases in time spent doing vigorous activity and increase in intensity of PA is generally associated with a protective effect on the knee joint except for knee joint effusion that worsened with increasing level of PA.

Do Total Knee Arthroplasty Patients Have a Higher Activity Level Compared to Patients With Osteoarthritis?

Background:Despite the alleviation of osteoarthritis (OA) symptoms that total knee arthroplasty (TKA) provides for patients with end-stage knee OA, recent studies have suggested that TKA may not increase physical activity levels. In this study, we compare the physical activity levels of patients with OA treated nonoperatively (non-TKA) with both patients who had received TKA (post-TKA) and patients who received TKA within 3 years of data collection (pre-TKA).Methods:Utilizing the Osteoarthritis Initiative database, accelerometry data were collected from non-TKA, pre-TKA, and post-TKA patients. Accelerometry data were subdivided by physical activity intensity levels, yielding daily minutes of each level of activity. Physical activity levels were then compared between non-TKA and pre-TKA/post-TKA patients. Physical activity levels for each patient were also compared to the Department of Health and Human Services (DHHS) guidelines for physical activity.Results:There was no difference in physical activity between non-TKA and pre-TKA patients, with the exception of non-TKA patients achieving more daily minutes of vigorous activity (P < .001). There was no difference in physical activity between non-TKA and post-TKA patients. Although 11.6% of non-TKA patients met DHHS guidelines, only 4.8% of pre-TKA and 5.3% of post-TKA patients met guidelines.Conclusion:Despite the improvements in patient-reported outcome measures following TKA, we found that TKA alone does not improve physical activity levels beyond those seen in the average patient with OA. In our study, the vast majority of patients with OA, treated nonoperatively or operatively, did not meet current DHHS guidelines for physical activity.

Vigorous exercise is associated with superior metabolic profiles in polycystic ovary syndrome independent of total exercise expenditure

To characterize metabolic features of women with polycystic ovary syndrome (PCOS) by exercise behavior and determine relative health benefits of different exercise intensities. Cross-sectional study. Tertiary academic institution. Three hundred and twenty-six women aged 14-52 years-old with PCOS by Rotterdam criteria examined between 2006 and2013. International Physical Activity Questionnaire (IPAQ) administered to classify patients into three groups based on Department of Health and Human Services (DHHS) Guidelines of vigorous, moderate, and inactive, along with physical examination and serum testing. Blood pressure, body mass index (BMI), waist circumference, fasting lipids, fasting glucose and insulin, 2-hour 75-gram oral glucose tolerance, homeostatic model assessment of insulin resistance (HOMA-IR). The DHHS guidelines for adequate physical activity were met by 182 (56%) women. Compared with moderate exercisers and inactive women, the vigorous exercisers had lower BMI and lower HOMA-IR; higher levels of high-density lipoprotein cholesterol and sex hormone-binding globulin; and a reduced prevalence of the metabolic syndrome. In a multivariate logistic regression analysis controlling for age, BMI, and total energy expenditure, every hour of vigorous exercise reduced a patient's odds of metabolic syndrome by 22% (odds ratio 0.78; 95% confidence interval, 0.62, 0.99). Women with PCOS who met DHHS guidelines for exercise demonstrated superior metabolic health parameters. Vigorous but not moderate activity is associated with reduced odds of the metabolic syndrome, independent of age, BMI, and total energy expenditure. PCOS patients should be encouraged to meet activity guidelines via vigorous physical activity.

Comparison of Physical Activity Levels in Physicians and Medical Students with the General Adult Population of the United States

Objective: Physicians who are physically fit have a higher likelihood of counseling their patients about physical activity. We sought to determine if the amount of physical activity in physicians and medical students differs from the general adult population of the United States and if geographic differences in physical activity levels exist. Methods: A cross-sectional survey was distributed to physicians and medical students throughout the United States to determine their level of physical activity according to US Department of Health and Human Services (DHHS) 2008 guidelines; data were collected from participants from June 2009 through January 2010. Our data set was compared with physical activity data from the Centers for Disease Control and Prevention (CDC) and we used geographic regions defined by the US Census Bureau. Results: Our survey respondents contained 631 attending physicians, 159 fellow physicians, 897 resident physicians, and 262 medical students. Only 64.5% of the general US adult population meets DHHS guidelines for physical activity, but 78% of the survey participants fulfilled the guidelines. The percentage of US adults who do not engage in leisure-time physical activity is 25.4% compared with 5.8% of survey participants. Survey respondents in the southern region had the lowest physical activity levels and participants in the western region had the highest levels. Conclusion: Physicians and medical students engage in more physical activity than the general US adult population. Regional differences in the general population's physical activity also persisted in physicians and medical students. Therefore, physicians who complete less physical activity may be less likely to encourage patients to engage in physical activity in geographic areas where the adult population is less active.

Initiation of Antiretroviral Therapy in Youth with HIV: A U.S.-Based Provider Survey

In 2009, the Department of Health and Human Services (DHHS) recommended initiating antiretroviral therapy (ART) for youth with HIV at higher CD4 counts (≤500 cells/mm³) than previously recommended (≤350 cells/mm³). Barriers experienced by providers regarding ART initiation in this population have not been assessed. From 12/2011-01/2012, we asked providers from the American Academy of HIV Medicine (AAHIVM) [corrected] listserv who prescribed ART to youth (ages 13-25 years) with behaviorally-acquired HIV to complete a web-based survey. We presented a clinical vignette to explore potential barriers for initiating ART. Overall, 274/290 (94%) respondents completed the survey. Most felt confident that evidence supported initiating ART at higher CD4 counts (94%), and that benefits outweighed the risks of long-term toxicity (98%) or developing resistance (88%). Most (96%) initiated ART in the patient vignette (age 19 years, CD4 count ~400). Patient characteristics (e.g., unstable housing or drug use) were perceived as large barriers to ART initiation. Low response rate (13%) was a limitation. Respondents were knowledgeable about relevant DHHS guidelines, believed sufficient evidence supported ART initiation at higher CD4 counts, and would provide treatment to those with CD4 counts ≤500cells/mm³. Understanding and overcoming barriers to initiation of ART perceived by providers is important to ensure implementation of ART treatment guidelines.

DHHS Guidelines Add Tenofovir/FTC/Elvitegravir/Cobicistat as an Alternative Regimen for First-Line HIV Treatment

The U.S. Department of Health and Human Services (DHHS) now recommends the single-tablet regimen tenofovir/FTC/elvitegravir/cobicistat (Stribild) as an alternative treatment for antiretroviral-naive HIV-infected patients with estimated creatinine clearance >70 mL/minute/1.73 m2. The new tablet was recently approved by the FDA for use in antiretroviral-naive HIV-infected patients based on the results of two …

Management of HIV infection in treatment-naive patients: a review of the most current recommendations.

The most current guidelines issued by the Department of Health and Human Services (DHHS) on the management of human immunodeficiency virus (HIV) infection in treatment-naive patients are reviewed. Treatment guidelines are updated frequently because of the emergence of data demonstrating the risks and benefits of antiretroviral therapy. The DHHS guidelines strongly recommend initiating therapy in patients with certain conditions regardless of CD4 cell count and in patients with CD4 cell counts of <350 cells/mm(3). Although supporting data are less definitive, treatment is also recommended for patients with CD4 cell counts of 350-500 cells/mm(3). Treatment for patients with CD4 cell counts of >500 cells/mm(3) is controversial. Although cumulative observational data and biological evidence support treatment at higher CD4 cell counts, randomized controlled trial data to support this are not available, and the risk of antiretroviral toxicities, resistance, non-adherence, and cost should be considered in individual patients. The preferred regimens have been consolidated to four options, including a dual-nucleoside reverse transcriptase inhibitor backbone (tenofovir plus emtricitabine) with a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir plus ritonavir or darunavir plus ritonavir), or an integrase strand-transfer inhibitor (raltegravir). Regimens are classified as alternative or acceptable when they have potential safety or efficacy concerns, have higher pill burdens, or require more-frequent administration compared with preferred regimens. The DHHS 2011 guidelines advocate earlier antiretroviral therapy initiation than recommended in recent years, and preferred regimens have been refined to maximize efficacy, safety, and quality of life for treatment-naive HIV-infected patients.

Updated DHHS and WHO Pediatric Antiretroviral Treatment Guidelines

During the past 2 months, both the U.S. Department of Health and Human Services (DHHS) and the WHO have released updated guidelines for treating

Head-to-head comparison of two first-line regimens and an nrti-sparing regimen for initial therapy of HIV-1 infection: What should we start?

Introduction: Over the past 12 years there has been signifi cant progress in the treatment of HIV-1 infection, starting with the use of potent three-drug combinations including a protease inhibitor (PI). In 1994, there were only four drugs approved by the US Food and Drug Administration, but now there are 24 approved agents in fi ve classes and four coformulations that simplify regimens. Despite this success, debate continues about the best initial regimen to start. The Department of Health and Human Services (DHHS) guidelines currently recommend two nucleoside reverse transcriptase inhibitors (NRTIs) in combination with either a non-NRTI (NNRTI) or a ritonavir-boosted PI (bPI) [1]. In particular, efavirenz (EFV) is the preferred NNRTI and lopinavir/ritonavir (LPV/r) is one of the preferred bPIs for fi rst-line therapy. Although there are pros and cons for each type of regimen, no preference is given. Furthermore, although regimens with a dual-NRTI backbone are most often used and have been recommended by the DHHS panel, the long-term side effects of NRTIs have sparked interest in non-NRTI–containing regimens [2,3]. The DHHS guidelines do not favor either approach and only state that the choice should be individualized, most often based on side effect profi les, drug–drug interactions, simplicity, and differences in risk of development of antiretroviral resistance. Overall, there are few comparative data for NNRTIbased versus PI-based regimens and few data on NRTI-sparing regimens. AIDS Clinical Trial Group (ACTG) 5142 was designed to evaluate effi cacy of three different types of regimens, one traditional bPI-based regimen, one traditional NNRTI-based regimen, and a novel two-drug NRTI-sparing regimen. The study enrolled patients at ACTG sites from January 2003 to May 2004.

WHO Updates HIV Treatment Recommendations

Almost simultaneously, the WHO and the U.S. Department of Health and Human Services (DHHS) released updated guidelines for HIV treatment. Both raised the CD4-cell–count threshold for starting treatment, and both refined their preferences for first-line regimens. The new WHO recommendations, outlined below, were published online in three rapid-advice documents, with the full set of guidelines expected in February 2010. (A complete review of the DHHS guidelines, by Dr. Abigail Zuger, is available here.)

Toward genetic rationalization of antiretroviral therapy for HIV

Daar et al. have extended the observations of Barbour et al. on the correlation between disease progression and standardized HIV polymerase activity in vitro. Polymerase thus joins accessory genes (nef rev tat vif vpr vpu reviewed in) as well as tropism-determining envelope as a potentially useful prognostic marker for disease progression and treatment initiation albeit one that must be functionally assayed (like envelope tropism) rather than genetically screened. For treatment-experienced patients reverse transcriptase and protease are already widely monitored for mutations predictive of drug resistance (reviewed). Thus Daar et al. provide one more step toward the individualization of antiretroviral therapy (ART) by fine tuning decisions made in the context of CD4 cell counts viremia and drug resistance. (excerpt)

HIV update: Emerging clinical evidence and a review of recommendations for the use of highly active antiretroviral therapy

This supplement will focus on recent trial data concerning the efficacy of certain nucleoside reverse transcriptase inhibitor (NRTI)-based highly active antiretroviral therapy (HAART) regimens, the most recent guidelines from the Department of Health and Human Services (DHHS) for the timing of antiretroviral (ARV) therapy initiation, and recommended ARV drug classes for managing treatment-naïve patients with HIV. When choosing an initial regimen for the treatment of HIV, it is important to carefully consider therapeutic goals. These goals include choosing HAART that is likely to maximally suppress viral replication, maintain or restore immunologic function, improve quality of life, and reduce HIV-related morbidity and mortality. The evidence-based DHHS guidelines recommend HAART regimens that are non-nucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-based. DHHS, however, does not recommend the use of triple-NRTI therapy for the initial treatment of HIV unless a preferred or alternative NNRTI- or PI-based regimen cannot be used. This recommendation concerning triple-NRTI therapy is supported by results from recent trials that demonstrated inferior outcomes with triple-NRTI-containing regimens compared with NNRTI- or PI-based HAART regimens. The timing for initiation of ARV therapy continues to change over time as the DHHS guidelines have evolved. Although the benefits of initiating ARV when CD4 cell count is < 200 cells/mm3 are well established, the use of early versus late initiation of ARV therapy in patients with CD4 cell counts > 200 cells/mm3 has its own benefits and drawbacks. To successfully manage people with HIV, it is crucial to find a balance between ARV potency, tolerability, safety, and convenience while providing durable viral suppression.