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Background Maintaining patient privacy when geocoding and linking residential address information with neighborhood-level data can create challenges during research. Challenges may arise when study staff have limited training in geocoding and linking data, or when non-study staff with appropriate expertise have limited availability, are unfamiliar with a study’s population or objectives, or are not affordable for the study team. Opportunities for data breaches may also arise when working with non-study staff who are not on-site. We detail a free, user-friendly protocol for constructing indices of the neighborhood risk environment during multisite, clinic-based cohort studies that rely on participants’ protected health information. This protocol can be implemented by study staff who do not have prior training in Geographic Information Systems (GIS) and can help minimize the operational costs of integrating geographic data into public health projects. Methods This protocol demonstrates how to: (1) securely geocode patients’ residential addresses in a clinic setting and match geocoded addresses to census tracts using Geographic Information System software (Esri, Redlands, CA); (2) ascertain contextual variables of the risk environment from the American Community Survey and ArcGIS Business Analyst (Esri, Redlands, CA); (3) use geoidentifiers to link neighborhood risk data to census tracts containing geocoded addresses; and (4) assign randomly generated identifiers to census tracts and strip census tracts of their geoidentifiers to maintain patient confidentiality. Results Completion of this protocol generates three neighborhood risk indices (i.e., Neighborhood Disadvantage Index, Murder Rate Index, and Assault Rate Index) for patients’ coded census tract locations. Conclusions This protocol can be used by research personnel without prior GIS experience to easily create objective indices of the neighborhood risk environment while upholding patient confidentiality. Future studies can adapt this protocol to fit their specific patient populations and analytic objectives.

Background: To obtain optimal health outcomes, persons living with human immunodeficiency virus (HIV) must be retained in clinical care. We examined the relationships between 4 possible combinations of 2 separate retention measures (missed visits and the Institute of Medicine [IOM] indicator) and all-cause mortality. Methods: The sample included 4162 antiretroviral therapy (ART)–naive patients who started ART between January 2000 and July 2010 at any of 5 US sites of the Center for AIDS Research Network of Integrated Clinical Systems. The independent variable of interest was retention, captured over the 12-month period after the initiation of ART. The study outcome, all-cause mortality 1 year after ART initiation, was determined by querying the Social Security Death Index or the National Death Index. We evaluated the associations of the 4 categories of retention with all-cause mortality, using the Cox proportional hazards models. Results: Ten percent of patients did not meet retention standards for either measure (hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.59–3.21). Patients retained by the IOM but not the missed-visits measure (42%) had a higher HR for mortality (1.72; 95% CI, 1.33–2.21) than patients retained by both measures (41%). Patients retained by the missed-visits but not the IOM measure (6%) had the same mortality hazards as patients retained by both measures (HR, 1.01; 95% CI, .54–1.87). Conclusions: Missed visits within the first 12 months of ART initiation are a major risk factor for subsequent death. Incorporating missed visits in clinical and public health retention and viral suppression programming is advised.

Background: Guidelines for initial antiretroviral treatment (ART) regimens have evolved, with integrase strand transfer inhibitors (INSTIs) increasingly prominent. Research on virologic failure (VF) with INSTI therapy is predominantly from clinical trials not care settings, especially for recently approved medications including dolutegravir. We compared outcomes among people living with HIV (PLWH) who initiated recommended regimens in clinical care across the United States. Setting: We examined 2 groups of PLWH at 8 clinics who initiated ART regimens (August 1, 2013-March 31, 2017): those ART treatment-naive at initiation, and those treatment-experienced. Methods: The outcome in this longitudinal cohort study was VF, defined as a viral load of ≥400 copies/mL ≥6 months after ART initiation. We examined the proportion of individuals who remained on, switched, or discontinued the regimen. Associations between regimens and outcomes were examined with adjusted Cox proportional hazards models. Results: Among 5177 PLWH, a lower proportion experienced VF on dolutegravir- versus other INSTI- or darunavir-based regimens for previously treatment-naive (7% vs. 12% vs. 28%) and treatment-experienced PLWH (6% vs. 10% vs. 21%). In adjusted analyses, hazard ratios were similar across regimens for the combined outcome of regimen discontinuation or treatment switch. The hazard ratios for VF comparing dolutegravir- to darunavir-based regimens was 0.30 (95% CI: 0.2 to 0.6) among previously treatment-naive PLWH and was 0.60 (95% CI: 0.4 to 0.8) among treatment-experienced PLWH. Conclusions: The proportion of previously treatment-naive PLWH remaining on recommended ART regimens did not differ by regimen. The likelihood of VF was lower with dolutegravir- than darunavir-based regimens for previously treatment-naive and treatment-experienced PLWH.

IMPORTANCE Antiretroviral therapy (ART) is the cornerstone of prevention and management of HIV infection. OBJECTIVE To evaluate new data and treatments and incorporate this information into updated recommendations for initiating therapy, monitoring individuals starting therapy, changing regimens, and preventing HIV infection for individuals at risk. EVIDENCE REVIEW New evidence collected since the International Antiviral Society-USA 2016 recommendations via monthly PubMed and EMBASE literature searches up to April 2018; data presented at peer-reviewed scientific conferences. A volunteer panel of experts in HIV research and patient care considered these data and updated previous recommendations. FINDINGS ART is recommended for virtually all HIV-infected individuals, as soon as possible after HIV diagnosis. Immediate initiation (eg, rapid start), if clinically appropriate, requires adequate staffing, specialized services, and careful selection of medical therapy. An integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is generally recommended for initial therapy, with unique patient circumstances (eg, concomitant diseases and conditions, potential for pregnancy, cost) guiding the treatment choice. CD4 cell count, HIV RNA level, genotype, and other laboratory tests for general health and co-infections are recommended at specified points before and during ART. If a regimen switch is indicated, treatment history, tolerability, adherence, and drug resistance history should first be assessed; 2 or 3 active drugs are recommended for a new regimen. HIV testing is recommended at least once for anyone who has ever been sexually active and more often for individuals at ongoing risk for infection. Preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and appropriate monitoring is recommended for individuals at risk for HIV. CONCLUSIONS AND RELEVANCE Advances in HIV prevention and treatment with antiretroviral drugs continue to improve clinical management and outcomes for individuals at risk for and living with HIV.

Background: Because HIV viral suppression is essential for optimal outcomes and prevention efforts, understanding trends and predictors is imperative to inform public health policy. Objective: To evaluate viral suppression trends in people living with HIV (PLWH), including the relationship of associated factors, such as demographic characteristics and integrase strand transfer inhibitor (ISTI) use. Design: Longitudinal observational cohort study. Setting: 8 HIV clinics across the United States. Participants: PLWH receiving clinical care. Measurements: To understand trends in viral suppression (≤400 copies/mL), annual viral suppression rates from 1997 to 2015 were determined. Analyses were repeated with tests limited to 1 random test per person per year and using inverse probability of censoring weights to address loss to follow-up. Joint longitudinal and survival models and linear mixed models of PLWH receiving antiretroviral therapy (ART) were used to examine associations between viral suppression or continuous viral load (VL) levels and demographic factors, substance use, adherence, and ISTI use. Results: Viral suppression increased from 32% in 1997 to 86% in 2015 on the basis of all tests among 31 930 PLWH. In adjusted analyses, being older (odds ratio [OR], 0.76 per decade [95% CI, 0.74 to 0.78]) and using an ISTI-based regimen (OR, 0.54 [CI, 0.51 to 0.57]) were associated with lower odds of having a detectable VL, and black race was associated with higher odds (OR, 1.68 [CI, 1.57 to 1.80]) (P < 0.001 for each). Similar patterns were seen with continuous VL levels; when analyses were limited to 2010 to 2015; and with adjustment for adherence, substance use, or depression. Limitation: Results are limited to PLWH receiving clinical care. Conclusion: HIV viral suppression rates have improved dramatically across the United States, which is likely partially attributable to improved ART, including ISTI-based regimens. However, disparities among younger and black PLWH merit attention.

Background: Efavirenz has been a mainstay of antiretroviral therapy (ART) for over 15 years in the US. Its association with neuropsychiatric side effects may influence clinical prescribing and management. Methods: We included HIV-infected adults enrolled in care at seven sites across the US, who initiated combination ART between 1999 and 2015. We examined the proportion initiating and continuing on efavirenz, overall and by mental health status. Log binomial and Cox models were used to estimate associations between mental health, clinical and sociodemographic characteristics and initiating or switching from efavirenz as first-line ART. Results: Of the 8,230 participants included, 3,710 (45%) initiated efavirenz. In multivariable analyses, prior mono- or dual-ART, ART initiation after 2006, being female, intravenous drug use, antidepressant prescription, previous mental health diagnosis and baseline CD4+ T-cell count >350 cells/mm3 were inversely associated with initiating efavirenz. Participants initiating efavirenz had a faster time to a regimen switch, compared with those initiating an efavirenz-free regimen (P-value

Reducing racial/ethnic disparities in human immunodeficiency virus (HIV) disease is a high priority. Reductions in HIV racial/ethnic disparities can potentially be achieved by intervening on important intermediate factors. The potential population impact of intervening on intermediates can be evaluated using observational data when certain conditions are met. However, using standard stratification-based approaches commonly employed in the observational HIV literature to estimate the potential population impact in this setting may yield results that do not accurately estimate quantities of interest. Here we describe a useful conceptual and methodological framework for using observational data to appropriately evaluate the impact on HIV racial/ethnic disparities of interventions. This framework reframes relevant scientific questions in terms of a controlled direct effect and estimates a corresponding proportion eliminated. We review methods and conditions sufficient for accurate estimation within the proposed framework. We use the framework to analyze data on 2,329 participants in the CFAR [Centers for AIDS Research] Network of Integrated Clinical Systems (2008-2014) to evaluate the potential impact of universal prescription of and ≥95% adherence to antiretroviral therapy on racial disparities in HIV virological suppression. We encourage the use of the described framework to appropriately evaluate the potential impact of targeted interventions in addressing HIV racial/ethnic disparities using observational data.

Marginal structural models for time-fixed treatments fit using inverse-probability weighted estimating equations are increasingly popular. Nonetheless, the resulting effect estimates are subject to finite-sample bias when data are sparse, as is typical for large-sample procedures. Here we propose a semi-Bayes estimation approach which penalizes or shrinks the estimated model parameters to improve finite-sample performance. This approach uses simple symmetric data-augmentation priors. Limited simulation experiments indicate that the proposed approach reduces finite-sample bias and improves confidence-interval coverage when the true values lie within the central “hill” of the prior distribution. We illustrate the approach with data from a nonexperimental study of HIV treatments.

Substance use disorders (SUDs) are thought to predict care discontinuity, though magnitude and substance-specific variance of effects are unclear. This report of analytic work undertaken with a multi-regional American cohort of 9153 care enrollees addresses these gaps. Care retention was computed from 24-month post-linkage clinic visit documentation, with SUD cases identified from patient-report screening instruments. Two generalized estimating equations tested binary and hierarchial SUD predictors of retention, and potential effect modification by patient age-group, sex, and care site. Findings demonstrate: (1) detrimental SUD effect, equivalent to a nine percentage-point decrease in retention, with independent effects of age-group and care site; (2) substance-specific effect of marijuana UD associated with lower retention; and (3) age-modification of each effect on care discontinuity, with SUDs serving as a risk factor among 18–29 year-olds and protective factor among 60+ year-olds. Collective findings document patient attributes as influences that place particular subgroups at-risk to discontinue care.

Objectives: Studies examining engagement in HIV care often capture cross-sectional patient status to estimate retention and identify predictors of attrition, which ignore longitudinal patient care-seeking behaviors. We describe the cyclical nature of (dis)engagement and re-entry into HIV care using the state transition framework. Design: We represent the dynamic patterns of patient care-retention using five states: engaged in care, missed one, two, three, or more expected visits, and deceased. Then we describe various care-seeking behaviors in terms of transitioning from one state to another (e.g. from disengaged to engaged). This analysis includes 31 009 patients enrolled in the Center for AIDS Research Network of Integrated Systems (CNICS) in the United States from 1996 to 2014. Method: Multistate models for longitudinal data were used to identify barriers to retention and subgroups at higher risk of falling out of care. Results: The initial 2 years following primary engagement in care were a crucial time for improving retention. Patients who had not initiated antiretroviral therapy, with lower CD4+ cell counts, higher viral load, or not having an AIDS-defining illness were less likely to be retained in care. Conclusion: Beyond the individual patient characteristics typically used to characterize retention in HIV care, we identified specific periods of time and points in the care continuum associated with elevated risk of transitioning out of care. Our findings can contribute to evidence-based recommendations to enhance long-term retention in CNICS. This approach can also be applied to other cohort data to identify retention strategies tailored to each population.

Results obtained in randomized trials may not easily generalize to target populations. Whereas in randomized trials the treatment assignment mechanism is known, the sampling mechanism by which individuals are selected to participate in the trial is typically not known and assuming random sampling from the target population is often dubious. We consider an inverse probability of sampling weighted (IPSW) estimator for generalizing trial results to a target population. The IPSW estimator is shown to be consistent and asymptotically normal. A consistent sandwich-type variance estimator is derived and simulation results are presented comparing the IPSW estimator with a previously proposed stratified estimator. The methods are then utilized to generalize results from two randomized trials of human immunodeficiency virus treatment to all people living with the disease in the USA.

Objective: To explore the effectiveness of raltegravir-based antiretroviral therapy (ART) on treatment response among ART-naive patients seeking routine clinical care. Design: Cohort study of adults enrolled in HIV care in the United States. Methods: We compared virologic suppression and CD4 + cell count recovery over a 2.5 year period after initiation of an ART regimen containing raltegravir or efavirenz using observational data from a US clinical cohort, generalized to the US population of people with diagnosed HIV. We accounted for nonrandom treatment assignment, informative censoring, and nonrandom selection from the US target population using inverse probability weights. Results: Of the 2843 patients included in the study, 2476 initiated the efavirenz-containing regimen and 367 initiated the raltegravir-containing regimen. In the weighted intent-To-Treat analysis, patients spent an average of 74 (95% confidence interval: 41, 106) additional days alive with a suppressed viral load on the raltegravir regimen than on the efavirenz regimen over the 2.5-year study period. CD4 + cell count recovery was also superior under the raltegravir regimen. Conclusion: Patients receiving raltegravir spent more time alive and suppressed than patients receiving efavirenz, but the probability of viral suppression by 2.5 years after treatment was similar between groups. Optimizing the amount of time spent in a state of viral suppression is important to improve survival among people living with HIV and to reduce onward transmission.

Increased scientific attention given to cannabis in the United States has particular relevance for its domestic HIV care population, given that evidence exists for both cannabis as a therapeutic agent and cannabis use disorder (CUD) as a barrier to antiretroviral medication adherence. It is critical to identify relative risk for CUD among demographic subgroups of HIV patients, as this will inform detection and intervention efforts. A Center For AIDS Research Network of Integrated Clinical Systems cohort (N = 10,652) of HIV-positive adults linked to care at seven United State sites was examined for this purpose. Based on a patient-report instrument with validated diagnostic threshold for CUD, the prevalence of recent cannabis use and corresponding conditional probabilities for CUD were calculated for the aggregate sample and demographic subgroups. Generalized estimating equations then tested models directly examining patient demographic indices as predictors of CUD, while controlling for history and geography. Conditional probability of CUD among cannabis-using patients was 49%, with the highest conditional probabilities among demographic subgroups of young adults and those with non-specified sexual orientation (67–69%) and the lowest conditional probability among females and those 50+ years of age (42% apiece). Similarly, youthful age and male gender emerged as robust multivariate model predictors of CUD. In the context of increasingly lenient policies for use of cannabis as a therapeutic agent for chronic conditions like HIV/AIDS, current study findings offer needed direction in terms of specifying targeted patient groups in HIV care on whom resources for enhanced surveillance and intervention efforts will be most impactful.

Background. The long-term effectiveness of human immunodeficiency virus (HIV) treatments containing integrase inhibitors is unknown. Methods. We use observational data from the Centers for AIDS Research Network of Integrated Clinical Systems and the Centers for Disease Control and Prevention to estimate 4-year risk of AIDS and all-cause mortality among 415 patients starting a raltegravir regimen compared to 2646 starting an efavirenz regimen (both regimens include emtricitabine and tenofovir disoproxil fumarate). We account for confounding and selection bias as well as generalizability by standardization for measured variables, and present both observational intent-to-treat and per-protocol estimates. Results. At treatment initiation, 12% of patients were female, 36% black, 13% Hispanic; median age was 37 years, CD4 count 321 cells/µL, and viral load 4.5 log10 copies/mL. Two hundred thirty-five patients incurred an AIDS-defining illness or died, and 741 patients left follow-up. After accounting for measured differences, the 4-year risk was similar among those starting both regimens (ie, intent-to treat hazard ratio [HR], 0.96 [95% confidence interval {CI}, .63–1.45]; risk difference, −0.9 [95% CI, −4.5 to 2.7]), as well as among those remaining on regimens (ie, per-protocol HR, 0.95 [95% CI, .59–1.54]; risk difference, −0.5 [95% CI, −3.8 to 2.9]). Conclusions. Raltegravir and efavirenz-based initial antiretroviral therapy have similar 4-year clinical effects. Vigilance regarding longer-term comparative effectiveness of HIV regimens using observational data is needed because large-scale experimental data are not forthcoming.

Prior efforts to estimate U.S. prevalence of substance use disorders (SUDs) in HIV care have been undermined by caveats common to single-site trials. The current work reports on a cohort of 10,652 HIV-positive adults linked to care at seven sites, with available patient data including geography, demography, and risk factor indices, and with substance-specific SUDs identified via self-report instruments with validated diagnostic thresholds. Generalized estimating equations also tested patient indices as SUD predictors. Findings were: (1) a 48 % SUD prevalence rate (between-site range of 21–71 %), with 20 % of the sample evidencing polysubstance use disorder; (2) substance-specific SUD rates of 31 % for marijuana, 19 % alcohol, 13 % methamphetamine, 11 % cocaine, and 4 % opiate; and (3) emergence of younger age and male gender as robust SUD predictors. Findings suggest high rates at which SUDs occur among patients at these urban HIV care sites, detail substance-specific SUD rates, and identify at-risk patient subgroups.

Background: Delaying HIV care initiation may lead to greater morbidity, mortality, and further HIV transmission. Rural residence may be associated with delayed diagnosis and linkage to care, with negative clinical outcomes. Objective: To examine the association between rural patient residence and CD4 cell count at HIV care initiation in a large HIV clinical cohort in the Southeastern United States. Methods: We included HIV-infected patients who initiated care between 1996 and 2012 with a geocodable address and no previous history of HIV clinical care. Patient residence was categorized as urban or rural using United States Department of Agriculture Rural Urban Commuting Area codes. Multivariable linear regression models were fit to estimate the association between patient residence and CD4 cell count at HIV care initiation. Results: Among 1396 patients who met study inclusion criteria, 988 had a geocodable address. Overall, 35% of patients resided in rural areas and presented to HIV care with a mean CD4 cell count of 351 cells/mm 3 (SD, 290). Care initiation mean CD4 cell counts increased from 329 cells/mm 3 (SD, 283) in 1996-2003 to 391 cells/mm 3 (SD, 292) in 2008-2012 (P = 0.006). Rural in comparison with urban patients presented with lower CD4 cell counts with an unadjusted and adjusted mean difference of -48 cells/mm 3 [95% confidence interval, -86 to -10) and -37 cells/mm 3 (95% confidence interval: -73 to -2), respectively, consistently observed across calendar years. Conclusions: HIV care initiation at low CD4 cell counts was common in this Southeastern US cohort and more common among rural area residents.

Background: Evidence about the effect of initiating efavirenz-containing combination antiretroviral therapy (ART) as the first-line therapy on suicidal thoughts remains conflicting. Methods: Using data from a cohort of HIV-infected adults enrolled in routine care across 5 sites in the United States, we included participants with a baseline patient-reported outcome measure and detectable viral load who initiated ART between 2011 and 2014. Participants were followed until the earliest of the following: first suicidal thoughts, discontinuation of initial ART regimen, death, loss to care (>12 months with no HIV appointments), or administrative censoring (2014-2015). Suicidal thoughts were measured using a Patient Health Questionnaire-9 item. We used weighted marginal structural Cox models to estimate the effect of initiating efavirenz-containing ART, versus efavirenz-free ART, on the hazard of active or passive suicidal thoughts after ART initiation, accounting for confounding by channeling bias. Results: Overall, 597 participants were followed for a median of 19 months (13, 132 total person-months); 147 (25%) initiated efavirenz-containing ART. At ART initiation, 38% of participants reported suicidal thoughts or depressive symptoms. Initiating efavirenz-based ART was associated with a hazard ratio (HR) for suicidal thoughts below the null in the crude analysis [HR, 0.88; 95% confidence interval (CI): 0.53 to 1.45] and above the null in the weighted analysis (HR, 1.21; 95% CI: 0.66 to 2.28). Among those with a prior mental health issue, the weighted HR was 1.76 (95% CI: 0.45 to 6.86). Conclusions: After accounting for measured channeling bias, we observed no strong evidence that initiating efavirenz-containing ART increased the hazard of suicidal thoughts.

We examined risk factors for advanced hepatic fibrosis [fibrosis-4 (FIB)-4 >3.25] including both current alcohol use and a diagnosis of alcohol use disorder among HIV-infected patients. Of the 12,849 patients in our study, 2133 (17%) reported current hazardous drinking by AUDIT-C, 2321 (18%) had a diagnosis of alcohol use disorder, 2376 (18%) were co-infected with chronic hepatitis C virus (HCV); 596 (5%) had high FIB-4 scores >3.25 as did 364 (15%) of HIV/HCV coinfected patients. In multivariable analysis, HCV (adjusted odds ratio (aOR) 6.3, 95% confidence interval (CI) 5.2–7.5), chronic hepatitis B (aOR 2.0, 95% CI 1.5–2.8), diabetes (aOR 2.3, 95% CI 1.8–2.9), current CD4 500 copies/mL (aOR 1.3, 95% CI 1.0–1.6) were significantly associated with advanced fibrosis. A diagnosis of an alcohol use disorder (aOR 1.9, 95% CI 1.6–2.3) rather than report of current hazardous alcohol use was associated with high FIB-4. However, among HIV/HCV coinfected patients, both current hazardous drinkers (aOR 1.6, 95% CI 1.1–2.4) and current non-drinkers (aOR 1.6, 95% CI 1.2–2.0) were more likely than non-hazardous drinkers to have high FIB-4, with the latter potentially reflecting the impact of sick abstainers. These findings highlight the importance of using a longitudinal measure of alcohol exposure when evaluating the impact of alcohol on liver disease and associated outcomes.

Background: Persons with human immunodeficiency virus (HIV) have higher risks for myocardial infarction (MI) than the general population. This is driven in part by higher type 2 MI (T2MI, due to coronary supply-demand mismatch) rates among persons with HIV (PWH). In the general population, T2MI has higher mortality than type 1 MI (T1MI, spontaneous and generally due to plaque rupture and thrombosis). PWH have a greater burden of comorbidities and may therefore have an even greater excess risk for complication and death in the setting of T2MI. However, mortality patterns after T1MI and T2MI in HIV are unknown. Methods: We analyzed mortality after MI among PWH enrolled in the multicenter, US-based Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort (N = 28,186). Incident MIs occurring between January 1, 1996, and December 31, 2014, were centrally adjudicated and classified as T1MI or T2MI. We first compared mortality following T1MI vs. T2MI among PWH. Cox survival analyses and Bayesian model averaging were then used to evaluate pre-MI covariates associated with mortality following T1MI and T2MI. Results: Among the 596 out of 28,186 PWH who experienced MI (2.1%; 293 T1MI and 303 T2MI), mortality rates were significantly greater after T2MI (22.2/100 person-years; 1-, 3-, and 5-year mortality 39%, 52%, and 62%) than T1MI (8.2/100 person-years; 1-, 3-, and 5-year mortality 15%, 22%, and 30%). Significant mortality predictors after T1MI were higher HIV viral load, renal dysfunction, and older age. Significant predictors of mortality after T2MI were low body-mass index (BMI) and detectable HIV viral load. Conclusions: Mortality is high following MI for PWH and substantially greater after T2MI than T1MI. Predictors of death after MI differed by type of MI, reinforcing the different clinical scenarios associated with each MI type and the importance of considering MI types separately.

Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen?. We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the “no direct effect” assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/μl compared with 500 cells/μl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The “no direct effect” assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.