Switching to Dolutegravir/Lamivudine Two-Drug Regimen: Durability and Virologic Outcomes by Age, Sex, and Race in Routine US Clinical Care.

Purpose: Two-drug regimens (2DR) may address drug-drug interactions and toxicity concerns. Dolutegravir/lamivudine (DTG/3TC) 2DR was approved in the US for both treatment-naïve and treatment-experienced individuals with a viral load <50 copies/mL. This study describes real-world DTG/3TC 2DR treatment outcomes among treatment-experienced individuals, stratified by age, sex, and race. Methods: From the OPERA® cohort, people with HIV with a viral load <50 copies/mL who switched from a commonly used three-drug regimen to DTG/3TC 2DR as per the label between April 8, 2019 and April 30, 2021 were included. Incidence rates (Poisson regression) for loss of virologic control (first viral load ≥50 copies/mL), confirmed virologic failure (2 viral loads ≥200 copies/mL or discontinuation after 1 viral load ≥200 copies/mL), and DTG/3TC 2DR discontinuation were estimated overall and stratified by age, sex, and race. Results: The 787 individuals included were followed for a median of 13.6 months (IQR: 8.2, 22.3). Confirmed virologic failure occurred in ≤5 individuals. Loss of virologic control occurred at a rate of 14.0 per 100 person-years (95% CI: 11.7, 16.8). DTG/3TC 2DR discontinuation occurred at a rate of 17.5 per 100 person-years (95% CI: 15.0, 20.3); 4% discontinued for treatment-related reasons (viremia, adverse diagnosis, side effect, lab abnormality). For all outcomes, incidence rates were comparable across strata of age, sex, and race. Conclusion: This descriptive study demonstrates that DTG/3TC 2DR is an effective and well-tolerated treatment option for people with HIV with a viral load <50 copies/mL at switch, regardless of their age, sex, or race.

A Comprehensive Literature Review of Treatment-Emergent Integrase Resistance with Dolutegravir-Based Regimens in Real-World Settings.

After a decade of dolutegravir (DTG) use in various antiretroviral therapy combinations and in diverse populations globally, it is critical to identify HIV strains with reduced drug susceptibility and monitor emergent resistance in people living with HIV who experience virologic failure while on DTG-based regimens. We searched the PubMed, Embase, and Cochrane databases to identify studies that reported DTG resistance-associated mutations (RAMs) emerging under selection pressure. Our review showed that RAMs conferring resistance to DTG were rare in 2-drug and 3-drug regimens used in real-world cohorts, corroborating data from clinical trials. The potency of DTG in maintaining virologic suppression was demonstrated, even in cases of pre-existing resistance to companion drugs in the regimen. Estimates of DTG RAMs depended on the population and certain risk factors, including monotherapy, baseline resistance or lack of genotypic testing, treatment history and prior virologic failure, and suboptimal treatment adherence. The RAMs detected after virologic failure, often in heavily treatment-experienced individuals with prior exposure to integrase strand transfer inhibitors, were G118R, E138K, G140A/C/R/S, Q148H/K/R, N155H, and R263K. Overall, these data highlight the durable effectiveness and high barrier to resistance of DTG as part of combination antiretroviral therapy in a wide variety of settings.

Heavily treatment-experienced people living with HIV in the OPERA® cohort: population characteristics and clinical outcomes.

BACKGROUND: Multi-class resistance, intolerance, and drug-drug interactions can result in unique antiretroviral (ART) combinations for heavily treatment-experienced (HTE) people living with HIV (PLWH). We aimed to compare clinical outcomes between HTE and non-HTE PLWH. METHODS: Eligible ART-experienced PLWH in care in the OPERA® Cohort were identified in a cross-sectional manner on December 31, 2016 and observed from the date of initiation of the ART regimen taken on December 31, 2016 until loss to follow up, death, study end (December 31, 2018), or becoming HTE (non-HTE group only). In the absence of resistance data, HTE was defined based on the ART regimens used (i.e., exposed to ≥ 3 core agent classes or regimen suggestive of HTE). Time to virologic undetectability, failure, and immunologic preservation were assessed using Kaplan-Meier methods; cumulative probabilities were compared between the two groups. Regimen changes, incident morbidities, and death were described. RESULTS: A total of 24,183 PLWH (2277 HTE PLWH, 21,906 non-HTE) were followed for a median of 28 months (IQR 21, 38). Viremic HTE PLWH (viral load [VL] ≥ 50 copies/mL) were less likely to achieve undetectability (VL < 50 copies/mL; 24-month cumulative probability: 80% [95% Confidence Interval 77-82]) than their non-HTE counterparts (85% [84-86]). No difference was observed in the probability of maintaining VLs < 200 copies/mL over the first 48 months after achieving suppression (< 50 copies/mL). HTE PLWH were less likely than non-HTE PLWH to maintain CD4 cell counts ≥ 200 cells/µL (24-month cumulative probability: 95% HTE [91-93]; 97% non-HTE [97-97]), and more likely to change regimens (45% HTE; 41% non-HTE). Incident non-AIDS defining event (ADE) morbidities were common in both populations, though more likely among HTE PLWH (45%) than non-HTE PLWH (35%). Incident ADE morbidities and deaths were uncommon among HTE (ADEs 5%; deaths 2%) and non-HTE (ADEs 2%; deaths 1%) PLWH. CONCLUSIONS: HTE PLWH were at greater risk of unfavorable treatment outcomes than non-HTE PLWH, suggesting additional therapeutic options are needed for this vulnerable population.

Changes in Body Mass Index Associated with Antiretroviral Regimen Switch Among Treatment-Experienced, Virologically Suppressed People Living with HIV in the United States.

With obesity on the rise among people living with HIV (PLWH), there is growing concern that weight gain may result as an undesired effect of antiretroviral therapy (ART). This analysis sought to assess the association between ART regimens and changes in body mass index (BMI) among ART-experienced, virologically suppressed PLWH. ART-experienced, virologically suppressed PLWH ≥18 years of age in the Observational Pharmacoepidemiology Research and Analysis (OPERA) cohort were included for analysis if prescribed a new regimen containing one of the following core agents: dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL), rilpivirine (RPV), or boosted darunavir (bDRV), for the first time between August 1, 2013 and December 31, 2017. Multivariable linear regression was used to assess the association between regimen and mean changes in BMI at 6, 12, and 24 months after switch. In unadjusted analyses, BMI increases ranged from 0.30 kg/m2 (bDRV) to 0.83 kg/m2 (RPV) at 24 months following switch, but gains were observed with every regimen. In adjusted analyses, compared to DTG, only bDRV was associated with a smaller increase in BMI at all time points, while EVG/c and RAL were associated with smaller increases in BMI at 6 months only. Overall, results were consistent in analyses stratified by baseline BMI category. BMI increases were relatively small but followed an upward trend over time in this cohort of treatment-experienced, suppressed PLWH. Gains were attenuated with a longer period of follow-up. BMI gains did not differ by regimens, except for bDRV regimens, which were consistently associated with smaller BMI increases than DTG.

Incident type 2 diabetes mellitus after initiation of common HIV antiretroviral drugs.

OBJECTIVES: To describe the prevalence and incidence of prediabetes and type 2 diabetes mellitus (T2DM) among people living with HIV (PLHIV) and evaluate the association between antiretroviral therapy (ART) initiation with dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL), or boosted darunavir (bDRV) and incident T2DM. DESIGN: Longitudinal study based on electronic health records of 29 674 PLHIV from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) cohort. METHODS: Calculate prevalence of prediabetes and T2DM at regimen initiation. Among PLHIV without prevalent disease, estimate prediabetes and T2DM incidence (Poisson regression) and association between regimen and incident T2DM (multivariate Cox proportional hazards regression). Analyses stratified by ART experience. RESULTS: Among ART-naive and ART-experienced/suppressed PLHIV, the estimated prevalence of prediabetes was 8 and 11%; that of T2DM was 4 and 10%, respectively. The T2DM incidence rate was 9 per 1000 person-years [95% confidence interval (CI): 8-11] among ART-naive and 13 per 1000 person-years (95% CI: 12-15) among ART-experienced/suppressed PLHIV, with no statistically significant differences between regimens. Compared with DTG, no statistically significant association between T2DM risk and regimen was observed among ART-naive on EVG/c [adjusted hazard ratios: 0.70 (95% CI: 0.47-1.05)] or bDRV [0.53 (0.26-1.04)] and ART-experienced/suppressed on EVG/c [0.96 (0.70-1.33)], RAL [1.17 (0.70-1.96)] or bDRV [0.90 (0.57-1.42)]. CONCLUSION: No increased risk of T2DM was observed with EVG/c, RAL or bDRV compared with DTG in ART-naive and experienced PLHIV. However, despite a large cohort, there was a small number of events and differential risk cannot be excluded.

Brief Report: Weight Gain Following ART Initiation in ART-Naïve People Living With HIV in the Current Treatment Era.

OBJECTIVES: Evaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era. METHODS: Between 2012 and 2019, 3232 ART-naïve PLWH initiated ≥3-drug ART regimens in 8 Centers for AIDS Research Network of Integrated Clinical Systems sites. We estimated weight change by regimen for 11 regimens in the immediate (first 6 months) and extended (all follow-up on initial regimen) periods using linear mixed models adjusted for time on regimen, interaction between time and regimen, age, sex, race/ethnicity, hepatitis B/C coinfection, nadir CD4, smoking, diabetes, antipsychotic medication, and site. We included more recently approved regimens [eg, with tenofovir alafenamide fumarate (TAF)] only in the immediate period analyses to ensure comparable follow-up time. RESULTS: Mean follow-up was 1.9 years on initial ART regimen. In comparison to efavirenz/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), initiating bictegravir/TAF/FTC {3.9 kg [95% confidence interval (CI): 2.2 to 5.5]} and dolutegravir/TAF/FTC [4.4 kg (95% CI: 2.1 to 6.6)] were associated with the greatest weight gain in the immediate period, followed by darunavir/TDF/FTC [3.7 kg (95% CI: 2.1 to 5.2)] and dolutegravir/TDF/FTC [2.6 kg (95% CI: 1.3 to 3.9)]. In the extended period, compared with efavirenz/TDF/FTC, initiating darunavir/TDF/FTC was associated with a 1.0 kg (95% CI: 0.5 to 1.5) per 6-months greater weight gain, whereas dolutegravir/abacavir/FTC was associated with a 0.6-kg (95% CI: 0.3 to 0.9) and dolutegravir/TDF/FTC was associated with a 0.6-kg (95% CI: 0.1 to 1.1) per 6-months greater gain. Weight gain on dolutegravir/abacavir/FTC and darunavir/TDF/FTC was significantly greater than that for several integrase inhibitor-based regimens. CONCLUSIONS: There is heterogeneity between regimens in weight gain following ART initiation among previously ART-naïve PLWH; we observed greater gain among PLWH taking newer integrase strand transfer inhibitors (DTG, BIC) and DRV-based regimens.

Two-drug antiretroviral regimens: an assessment of virologic response and durability among treatment-experienced persons living with HIV in the OPERA® Observational Database.

INTRODUCTION: Two-drug regimens (2-DR) have the potential to be a viable solution to the challenges of treatment complexity, cost, adverse effects and contraindications. We sought to describe the real-world use and effectiveness of 2-DR among persons living with HIV (PLHIV) in the United States. METHODS: We analysed data for 10,190 treatment-experienced patients from the OPERA® Observational Database initiating a new 2-DR or three-drug regimen (3-DR) between 1 January 2010 and 30 June 2016. Multivariate Cox Proportional Hazards models were used to estimate the association among 2-DR or 3-DR initiation and virologic suppression (viral load (VL) <50 copies/mL), virologic failure (2 VLs > 200 copies/mL or 1 VL > 200 copies/mL + discontinuation) or regimen discontinuation. RESULTS: Patients initiating a 2-DR (n = 1337, 13%) were older, and more likely to have a lower CD4 count, a history of AIDS and comorbid conditions than patients initiating a 3-DR. There was no difference between groups in time to virologic suppression (aHR: 1.00 (95% CI: 0.88, 1.13)) among viraemic patients (baseline VL ≥ 50 copies/mL, n = 4180), or time to virologic failure (aHR: 1.15 (95% CI: 0.90, 1.48)) among virologically stable patients (baseline VL < 50 copies/mL, n = 6010). However, time to discontinuation was shorter following 2-DR than 3-DR initiation (aHR: 1.51 (95% CI: 1.41, 1.61)). CONCLUSIONS: In this large cohort of treatment-experienced patients, 2-DR prescriptions were common and more frequent among patients with significant comorbidity. Virologic response was similar, but duration of use was shorter with a 2-DR than a 3-DR, suggesting that 2-DRs may be a virologically effective treatment strategy for treatment-experienced PLHIV with existing comorbidities.

Integrase Inhibitor-Based Antiretroviral Therapy Among Women Living with HIV: Data from the OPERA Cohort.

BACKGROUND: Women face unique complexities in HIV treatment yet are underrepresented in antiretroviral therapy (ART) studies. OBJECTIVE: This analysis assessed the one-year durability of the first integrase strand transfer inhibitor (INSTI)-based regimens prescribed to women in a large cohort of patients living with HIV in care. METHODS: Women with HIV who initiated their first INSTI-containing regimen between 08/12/2013 and 11/30/2015 were identified in the OPERA cohort, a collaboration of 79 US outpatient clinics. Discontinuation within the first year of treatment with an INSTI was compared between dolutegravir (DTG), raltegravir (RAL) and elvitegravir (EVG), using multivariable Cox regression and Kaplan- Meier estimates. Virologic response and regimen modifications were described and compared across INSTIs. RESULTS: A total of 537 treatment-naïve (DTG: 39%, EVG: 48%, RAL: 13%) and 878 treatmentexperienced (DTG: 57%, EVG: 29%, RAL: 13%) women were analyzed. In the first twelve months after initiation, women taking EVG or RAL were more likely to discontinue their initial INSTI than those taking DTG among both treatment-naïve (adjusted hazard ratio EVG vs. DTG: 1.59 (95% CI: 1.09, 2.39); RAL vs. DTG: 2.46 (1.49, 4.05)) and treatment-experienced women (EVG vs. DTG: 1.39 (1.02, 1.88); RAL vs. DTG: 2.17 (1.51, 3.12)). Following discontinuation of the initial INSTI, women commonly switched to a regimen containing a different drug from the INSTI class (treatment-naïve DTG: 34%, RAL: 33% EVG: 41%; treatment-experienced DTG: 23%, RAL: 19% EVG: 41%). CONCLUSION: In treatment-naïve and treatment-experienced women living with HIV, women taking DTG had the lowest risk for early (≤1 year) discontinuation.

Prevalence of pretreatment and acquired HIV-1 mutations associated with resistance to lamivudine or rilpivirine: a systematic review.

BACKGROUND: Pretreatment and acquired drug resistance mutations (DRMs) can limit antiretroviral therapy effectiveness. METHODS: We review prevalence of DRMs with resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), focusing on lamivudine and rilpivirine, from 127 articles with >100,000 individuals with HIV-1 infection. RESULTS: Estimated global prevalence of pretreatment resistance to any NRTI was 4% and to any NNRTI was 6%. Most prevalent DRMs resistant to lamivudine or rilpivirine were at positions E138 (4%), V179 (1%) and M184 (1%). Estimated acquired DRM prevalence was 58% for any NRTIs and 67% for any NNRTIs, most frequently at positions M184 (58%) and Y181 (21%). CONCLUSIONS: This review suggests low risk of lamivudine- or rilpivirine-resistant mutations in treatment-naive, HIV-1-infected individuals.

HLA-B*57:01 screening and hypersensitivity reaction to abacavir between 1999 and 2016 in the OPERA® observational database: a cohort study.

BACKGROUND: HLA-B*57:01 screening was added to clinical care guidelines in 2008 to reduce the risk of hypersensitivity reaction from abacavir. The uptake of HLA-B*57:01 screening and incidence of hypersensitivity reaction were assessed in a prospective clinical cohort in the United States to evaluate the effectiveness of this intervention. METHODS: We included all patients initiating an abacavir-containing regimen for the first time in the pre-HLA-B*57:01 screening period (January 1, 1999 to June 14, 2008) or the post-HLA-B*57:01 screening period (June 15, 2008 to January 1, 2016). Yearly incidence of both HLA-B*57:01 screening and physician panel-adjudicated hypersensitivity reactions were calculated and compared. RESULTS: Of the 9619 patients eligible for the study, 33% initiated abacavir in the pre-screening period and 67% in the post-screening period. Incidence of HLA-B*57:01 screening prior to abacavir initiation increased from 43% in 2009 to 84% in 2015. The incidence of definite or probable hypersensitivity reactions decreased from 1.3% in the pre-screening period to 0.8% in 2009 and further to 0.2% in 2015 in the post-screening period. CONCLUSIONS: Frequency of HLA-B*57:01 screening increased steadily since its first inclusion in treatment guidelines in the United States. This increase in screening was accompanied by a decreasing incidence of definite or probable hypersensitivity reactions over the same period. However, a considerable proportion of patients initiating abacavir were not screened, representing a failed opportunity to prevent hypersensitivity reactions. Where HLA-B*57:01 screening is standard of care, patients should be confirmed negative for this allele before starting abacavir treatment.

Abacavir Hypersensitivity Reaction Reporting Rates During a Decade of HLA-B*5701 Screening as a Risk-Mitigation Measure.

INTRODUCTION: Human leukocyte antigen (HLA)-B*5701 screening identifies patients at increased risk for abacavir (ABC) hypersensitivity reaction (HSR). Screening was adopted in GlaxoSmithKline and ViiV Healthcare clinical trials in 2007 and human immunodeficiency virus treatment guidelines in 2008. Company meta-analyses of trials pre-HLA-B*5701 screening reported HSR rates of 4-8%. We analyzed the effectiveness of HLA-B*5701 screening on reducing HSR rates using clinical trial, Observational Pharmaco-Epidemiology Research & Analysis (OPERA) cohort, and spontaneous reporting data. METHODS: A meta-analysis examined 12 trials in 3063 HLA-B*5701-negative patients receiving an ABC-containing regimen from April 9, 2007, to September 22, 2015. Potential cases were identified using prespecified Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (drug hypersensitivity, hypersensitivity, anaphylactic reaction, anaphylaxis) and adjudicated against a Company ABC HSR case definition. Investigator-diagnosed cases were identified and rates were calculated. In the OPERA cohort, 9619 patients initiating their first ABC-containing regimen from January 1, 1999, to January 1, 2016, were identified. Patients were observed from regimen start until the earliest-following censoring event: ABC discontinuation, loss to follow-up, death, or study end (July 31, 2016). OPERA physicians evaluated events against OPERA definitions for definite/probable cases of ABC HSR; rates were calculated pre- and post-2008. The Company case definition was used to identify spontaneously reported cases for four marketed ABC-containing products; reporting rates were calculated using estimated exposure from sales data, through December 31, 2016. RESULTS: Suspected ABC HSR rates were 1.3% or less in the meta-analysis. In the OPERA cohort, the rate was 0.4% among patients initiating ABC post-2008 versus 1.3% pre-2008 (p<0.0001). Spontaneous reporting rates were low post-2008 (54 to 22 cases per 100,000 patient-years exposure [PYE]) versus pre-2008 (618 to 55 cases per 100,000 PYE). CONCLUSIONS: Clinically suspected ABC HSR rates were 1.3% or less in HLA-B*5701-negative patients. Recognizing their limitations, data from the OPERA cohort and spontaneous reporting indicate that HLA-B*5701 screening has reduced reporting rates of suspected HSR in clinical practice. Where screening for HLA-B*5701 is standard care, patients should be confirmed negative for this allele before starting ABC treatment.

Psychiatric outcomes observed in patients living with HIV using six common core antiretrovirals in the Observational Pharmaco-Epidemiology Research and Analysis database.

BACKGROUND: Psychiatric outcomes are common among people living with HIV and may be associated with specific antiretroviral use. We evaluated the occurrence of psychiatric outcomes in patients taking dolutegravir (DTG)-containing regimens compared with five other core agents. METHODS: Patients in the OPERA database prescribed regimens based on DTG, efavirenz (EFV), raltegravir (RAL), darunavir (DRV), rilpivirine (RPV), or elvitegravir (EVG) for the first time between 1 January 2013 and 31 December 2015 were analyzed. Psychiatric outcomes included diagnoses of anxiety, depression, insomnia, or suicidality during core agent exposure. Multivariable Cox analysis models were used to assess time to psychiatric outcomes between core agents stratified by psychiatric history, with DTG as the referent. RESULTS: A total of 13,261 patients initiated a regimen of interest (DTG: 2783; RAL: 979; EVG: 3895, EFV: 1746, RPV: 1921, DRV: 1937). Psychiatric history was common, with varied prevalence across groups (DTG 38%, EFV 24%, RAL 40%, DRV 34%, RPV 29%, EVG 31%). Among patients without a psychiatric history, the likelihood of a psychiatric outcome during follow up did not differ between DTG and the other core agents. Among patients with a psychiatric history, risk during follow up for patients taking DTG was equivalent (versus RPV), marginally reduced (versus RAL and EFV), or reduced (versus EVG and DRV). CONCLUSIONS: In a large cohort of HIV+ patients in care, patients with a psychiatric history appeared channeled towards drugs with known favorable psychiatric safety profiles, including DTG. Despite this, DTG exposure was not associated with an increased risk of psychiatric outcomes during follow up in patients with or without a psychiatric history.

Virologic Effectiveness of Abacavir/Lamivudine with Darunavir/Ritonavir Versus Other Protease Inhibitors in Treatment-Experienced HIV-Infected Patients in Clinical Practice.

BACKGROUND AND OBJECTIVES: The standard of care for HIV treatment is a three-drug regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and either a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor (PI) or an integrase strand transfer inhibitor. Darunavir boosted with ritonavir (DRV/r) is the only preferred PI in the US Department of Health and Human Services (DHHS) HIV treatment guidelines for antiretroviral-naïve patients, recommended in combination with tenofovir/emtricitabine for antiretroviral-naïve patients. For treatment-experienced and certain antiretroviral-naïve patients, abacavir and lamivudine (ABC/3TC) in combination with DRV/r is considered an effective and tolerable alternative, despite limited research on the effectiveness of this particular combination. This study evaluated virologic outcomes in treatment-experienced patients taking ABC/3TC + DRV/r compared to treatment-experienced patients taking ABC/3TC with any other PI. METHODS: Treatment-experienced HIV-infected patients initiating their first regimen containing ABC/3TC in combination with any PI in the year 2005 or later were selected from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA®) cohort, a prospective observational cohort reflecting routine medical care. Viral load measurements taken during follow-up were compared between patients taking ABC/3TC + DRV/r and ABC/3TC with a PI other than DRV/r. Logistic regression models were fit to assess the association between regimen exposure and viral load suppression. RESULTS: A total of 151 patients initiating ABC/3TC + DRV/r and 525 patients initiating ABC/3TC + a non-darunavir PI were included. Patients in both treatment groups had comparable clinical indicators (viral load, CD4) at baseline. A regimen of ABC/3TC + DRV/r was more likely to be prescribed in the later years of the study period, leading to a shorter median follow-up in the DRV/r treatment group (as-treated analysis: 14 vs. 17 months, p = 0.04; intent-to-treat analysis: 33 vs. 68 months, p < 0.001). Multivariable logistic regression models accounting for year of regimen initiation, among other factors, indicated no statistically significant differences in achieving an undetectable viral load for patients taking DRV/r with ABC/3TC compared with other PIs, both in the as-treated (odds ratio [95 % confidence interval]: 0.84 [0.53-1.34]) and intent-to-treat analyses (0.82 [0.48-1.40]). Patients in both treatment groups also showed similar reductions in viral load (median darunavir vs. non-darunavir: -23.0 vs. -23.0 copies/mL; p = 0.72) and gains in CD4 T cell counts (median darunavir vs. non-darunavir: 106 vs. 108 cells/mm3; p = 0.59] while being treated with the regimen of interest. CONCLUSIONS: Patients receiving ABC/3TC + DRV/r appear to experience similar treatment benefit to patients taking ABC/3TC with other PIs in terms of achieving suppression, as well as absolute reductions in viral load and CD4 lymphocyte gains.

Effect of pregnancy and the postpartum period on adherence to antiretroviral therapy among HIV-infected women established on treatment.

: Among women who become pregnant after initiating highly active antiretroviral therapy (HAART), few data describe the effect of pregnancy and postpartum on adherence. We conducted a retrospective clinical cohort study among therapy-naive women (age, 18-45 years) initiating HAART in Johannesburg, South Africa. Among 7510 women in our analysis, 896 experienced a pregnancy after starting HAART. Compared with nonpregnant periods of follow-up, there was an increased risk of nonadherence during the postpartum period (weighted risk ratio: 1.46, 95% confidence interval: 1.17 to 1.82) but not during pregnancy itself (weighted risk ratio: 0.95, 95% confidence interval: 0.78 to 1.17).

Comparison of pharmacy-based measures of adherence to antiretroviral therapy as predictors of virological failure.

We compared multiple pharmacy refill-based adherence indicators for antiretroviral therapy, as well as thresholds for defining non-adherent behavior, based on ability to predict virological failure. A total of 29,937 pharmacy visits with corresponding viral load assessments were contributed by 8,695 patients attending a large clinic in Johannesburg, South Africa. Indicators based on pill coverage and timing of refill pickup performed comparably using the strictest thresholds for adherence [100 % pill coverage: odds ratio (OR) (95 % confidence interval (CI)) : 1.26 (1.15, 1.39); prescription picked up on or before scheduled refill date: 1.27 (1.16,1.38)]. For both types of indicators, the association between non-adherence and virological failure increased as the threshold defining adherent behavior was lowered. All measures demonstrated high specificity (range 84-98 %), but low sensitivity (5-19 %). In this setting, patients identified as non-adherent using pharmacy-based indicators are likely correctly classified and in need of interventions to improve compliance. Pharmacy based measures alone, however, are inadequate for identifying most cases of nonadherence.