Maternal Response to Antiretroviral Therapy in Johannesburg, South Africa: Adherence and Drug Toxicities

South Africa has one of the highest HIV prevalences in the world, with women of reproductive age disproportionately affected by the epidemic. Access to lifesaving highly active antiretroviral therapy (HAART) is expanding in the region, and many HIV-positive women are experiencing pregnancy after initiating lifelong treatment with HAART. The benefits of continued treatment with HAART during pregnancy include prevention of mother-to-child transmission of HIV, as well as maximization of maternal health. Optimal effectiveness of HAART, however, is dependent on a complex set of factors, most of which have not been adequately described in women established on HAART prior to pregnancy. Using high quality observational data from a large clinical HIV cohort in Johannesburg, South Africa, and robust epidemiologic methods, including inverse probability weighted marginal structural models, we examined maternal responses to HAART among women established on treatment at the time of pregnancy. An optimal adherence indicator was derived from routinely collected antiretroviral drug refill data from nearly 9,000 adult HIV-positive men and women, and evaluated based on ability to predict virological failure among the non-adherent. In our cohort of 7,510 HIV-positive women on treatment, pregnancy was common after HAART initiation, with 896 women experiencing at least one pregnancy during follow-up. Risk of non-adherence was similar among non-pregnant and pregnant women (weighted Risk Ratio (RR): 0.95, 95% confidence interval (CI): 0.78 1.17), while women in the postpartum period, defined as six months after birth, experienced an increased risk of non-adherence compared to non-pregnant women (weighted RR: 1.46, 95% CI: 1.17, 1.82). Among the women in our cohort, we also observed few serious adverse events of renal impairment related to use of tenofovir, a widely used first-line agent in HAART regimens, regardless of pregnancy exposure. Despite limitations of our pregnancy exposure data, our findings were robust to sensitivity analyses. In general, our results suggest that for women established on treatment prior to conceiving, continuation of HAART through pregnancy does not seem to increase maternal risks in respect to adherence or renal toxicity related to tenofovir use.Doctor of Philosoph

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 (ages 18–45) initiating HAART in Johannesburg, South Africa. Among 7,510 women in our analysis, 896 experienced a pregnancy after starting HAART. Compared to non-pregnant periods of follow-up, there was an increased risk of non-adherence during the postpartum period (weighted risk ratio (RR): 1.46, 95% confidence interval (CI): 1.17, 1.82), but not during pregnancy itself (weighted RR: 0.95, 95% CI: 0.78, 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

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

Abstract 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

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

ObjectivesEvaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era.MethodsBetween 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.ResultsMean 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.ConclusionsThere 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

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