A pharmacokinetic and pharmacogenetic evaluation of contraceptive implants and antiretroviral therapy among women in Kenya and Uganda.
Ontology highlight
ABSTRACT:
SUBMITTER: Patel RC
PROVIDER: S-EPMC6774811 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
A pharmacokinetic and pharmacogenetic evaluation of contraceptive implants and antiretroviral therapy among women in Kenya and Uganda.
Patel Rena C RC Stalter Randy M RM Thomas Katherine K KK Tamraz Bani B Blue Steven W SW Erikson David W DW Kim Christina J CJ Kelly Edward J EJ Nanda Kavita K Kourtis Athena P AP Lingappa Jairam R JR Mugo Nelly N Baeten Jared M JM Scarsi Kimberly K KK
AIDS (London, England) 20191101 13
<h4>Objectives</h4>To evaluate pharmacokinetics and pharmacogenetics of contraceptive implant progestin concentrations in HIV-positive women initiating efavirenz (EFV)-containing or nevirapine (NVP)-containing antiretroviral therapy (ART).<h4>Design</h4>We analyzed stored samples from women self-reporting implant use in the Partners PrEP Study.<h4>Methods</h4>Plasma samples collected every 6 months were analyzed for levonorgestrel and etonogestrel concentrations. Progestin concentrations from sa ...[more]
Similar Datasets
Project description:Background: Women living with HIV have the right to choose whether, when and how many children to have. Access to antiretroviral therapy (ART) and contraceptives, including implants, continues to increase due to a multitude of efforts. In Kenya, 4.8% of adults are living with HIV, and in 2017, 54% were receiving an efavirenz-based ART regimen. Meanwhile, 16.1% of all Kenyan married (and 10.4% of unmarried) women used implants. Studies have reported drug interactions leading to contraceptive failures among implant users on ART. This retrospective record review aimed to determine unintentional pregnancy rates among women 15-49 years of age, living with HIV and concurrently using implants and ART in western Kenya between 2011 and 2015. Methods: We reviewed charts of women with more than three months of concurrent implant and ART use. Implant failure was defined as implant removal due to pregnancy or birth after implant placement, but prior to scheduled removal date. The incidence of unintended pregnancy was calculated by woman-years at risk, assuming a constant rate. Results: Data from 1,152 charts were abstracted, resulting in 1,190 implant and ART combinations. We identified 115 pregnancies, yielding a pregnancy incidence rate of 6.32 (5.27-7.59), with 9.26 among ETG and 4.74 among LNG implant users, respectively. No pregnancies were recorded among women on non-NNRTI-based regimens, whereas pregnancy rates for efavirenz and nevirapine-containing regimens were similar, at 6.41 (4.70-8.73) and 6.44 (5.13-8.07), respectively. Conclusions: Our findings highlight the implications of drug interaction on women's choices for contraception.
| S-EPMC6996231 | biostudies-literature
Project description:BackgroundDrug-drug interactions between orally administered antiretroviral therapy (ART) and hormones released from an intravaginal ring are not known. We hypothesised that ART containing either efavirenz or ritonavir-boosted atazanavir would alter plasma concentrations of vaginally administered etonogestrel and ethinylestradiol but that ART concentrations would be unchanged during use of an intravaginal ring.MethodsWe did a parallel, three-group, pharmacokinetic evaluation at HIV clinics in Asia (two sites), South America (five), sub-Saharan Africa (three), and the USA (11) between Dec 30, 2014, and Sept 12, 2016. We enrolled women with HIV who were either ART-naive (control group; n=25), receiving efavirenz-based ART (n=25), or receiving atazanavir-ritonavir-based ART (n=24). Women receiving ART were required to be on the same regimen for at least 30 days, with 400 copies or less per mL of plasma HIV-1 RNA; women not receiving ART had CD4 counts of 350 cells per μL or less. We excluded participants who had a bilateral oophorectomy or conditions that were contraindicated in the intravaginal ring product labelling. An intravaginal ring releasing etonogestrel and ethinylestradiol was inserted at entry (day 0). Single plasma samples for hormone concentrations were collected on days 7, 14, and 21 after intravaginal ring insertion. The primary outcome was the plasma concentration of etonogestrel and ethinylestradiol on day 21. Etonogestrel and ethinylestradiol concentrations were compared between each ART group and the control group by geometric mean ratio (GMR) with 90% CIs and Wilcoxon rank-sum test. As secondary outcomes, efavirenz or ritonavir-boosted atazanavir concentrations were assessed by 8-h intensive pharmacokinetic sampling at entry before intravaginal ring insertion and before intravaginal ring removal on day 21. Antiretroviral areas under the concentration-time curve (AUC0-8 h) were compared before and after intravaginal ring insertion by GMR (90% CI) and Wilcoxon signed-rank test. This study is registered with ClinicalTrials.gov, number NCT01903031.FindingsBetween Dec 30, 2014, and Sept 12, 2016, we enrolled 84 participants in the study; ten participants were excluded from the primary hormone analysis. 74 participants met the primary endpoint: 25 in the control group, 25 in the efavirenz group, and 24 in the atazanavir group. On day 21 of intravaginal ring use, participants receiving efavirenz had 79% lower etonogestrel (GMR 0·21, 90% CI 0·16-0·28; p<0·0001) and 59% lower ethinylestradiol (0·41, 0·32-0·52; p<0·0001) concentrations compared with the control group. By contrast, participants receiving ritonavir-boosted atazanavir had 71% higher etonogestrel (1·71, 1·37-2·14; p<0·0001), yet 38% lower ethinylestradiol (0·62, 0·49-0·79; p=0·0037) compared with the control group. The AUC0-8 h of efavirenz or atazanavir did not differ between the groups.InterpretationHormone exposure was significantly lower when an intravaginal ring contraceptive was combined with efavirenz-based ART. Further studies designed to examine pharmacodynamic endpoints, such as ovulation, when intravaginal ring hormones are combined with efavirenz are warranted.FundingNational Institutes of Health, through the AIDS Clinical Trials Group and the International Maternal Pediatric Adolescent AIDS Clinical Trials Network, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.
| S-EPMC6765389 | biostudies-literature
Project description:Considerable debate exists concerning the effects of antiretroviral therapy (ART) service scale-up on non-HIV services and overall health system performance in sub-Saharan Africa. In this study, we examined whether ART services affected trends in non-ART outpatient department (OPD) visits in Kenya and Uganda.Using a nationally representative sample of health facilities in Kenya and Uganda, we estimated the effect of ART programs on OPD visits from 2007 to 2012. We modeled the annual percent change in non-ART OPD visits using hierarchical mixed-effects linear regressions, controlling for a range of facility characteristics. We used four different constructs of ART services to capture the different ways in which the presence, growth, overall, and relative size of ART programs may affect non-ART OPD services.Our final sample included 321 health facilities (140 in Kenya and 181 in Uganda). On average, OPD and ART visits increased steadily in Kenya and Uganda between 2007 and 2012. For facilities where ART services were not offered, the average annual increase in OPD visits was 4·2% in Kenya and 13·5% in Uganda. Among facilities that provided ART services, we found average annual OPD volume increases of 7·2% in Kenya and 5·6% in Uganda, with simultaneous annual increases of 13·7% and 12·5% in ART volumes. We did not find a statistically significant relationship between annual changes in OPD services and the presence, growth, overall, or relative size of ART services. However, in a subgroup analysis, we found that Ugandan hospitals that offered ART services had statistically significantly less growth in OPD visits than Ugandan hospitals that did not provide ART services.Our findings suggest that ART services in Kenya and Uganda did not have a statistically significant deleterious effects on OPD services between 2007 and 2012, although subgroup analyses indicate variation by facility type. Our findings are encouraging, particularly given recent recommendations for universal access to ART, demonstrating that expanding ART services is not inherently linked to declines in other health services in sub-Saharan Africa.
| S-EPMC5559797 | biostudies-other
Project description:BackgroundPharmacokinetic data are lacking for progestin-releasing subdermal contraceptive implants when used with either rilpivirine- or darunavir/ritonavir-based ART.ObjectivesTo characterize the pharmacokinetics of etonogestrel or levonorgestrel implants when administered with these ART regimens over 48 weeks.Patients and methodsTwo separate, parallel, three-group, non-randomized, pharmacokinetic studies evaluated either etonogestrel or levonorgestrel in women receiving rilpivirine- or darunavir-based ART compared with women without HIV (control group). Participants on ART were switched to rilpivirine-based ART with a run-in period of 6 weeks or darunavir-based ART with a run-in of 2 weeks prior to implant insertion. Plasma was collected on Day 0, and 1, 4, 12, 24, 36 and 48 weeks post-insertion. Plasma progestin concentrations were compared between ART and control groups by geometric mean ratio (GMR) and 90% CI.ResultsAt the primary endpoint of Week 24, progestin concentrations were similar between the rilpivirine and control groups [etonogestrel: 1.18 (0.99-1.37); levonorgestrel: 1.16 (0.97-1.33)]. At Week 24, progestin exposure was higher in the darunavir groups compared with the control group [etonogestrel: 2.56 (1.69-3.28); levonorgestrel: 1.89 (1.38-2.29)]. Results remained consistent through to Week 48. No differences in etonogestrel-related adverse events were observed, but both ART groups experienced more menstrual abnormalities versus the control group with levonorgestrel.ConclusionsEtonogestrel and levonorgestrel concentrations were not altered by rilpivirine-based ART. Although progestin concentrations were higher in the ART groups containing ritonavir-boosted darunavir, no implant-related serious adverse events were observed. Both progestin-releasing implants are an appropriate contraceptive option with either rilpivirine- or darunavir/ritonavir-based ART.
| S-EPMC10205603 | biostudies-literature
Project description:BackgroundHIV-infected youth in sub-Saharan Africa are less likely to initiate antiretroviral therapy (ART) than older adults.Setting and methodsAdult (≥15 years) residents enumerated during a census in 32 communities in rural Kenya and Uganda named social contacts in 5 domains: health, money, emotional support, food, and free time. Named contacts were matched to other enumerated residents to build social networks among 150,395 adults; 90% were tested for HIV at baseline. Among youth (15-24 years) who were ART naive at baseline (2013-2014), we evaluated whether having ≥1 network contact who was HIV infected predicted ART initiation within 3 years and modification of this association by age and strength of contact, using logistic regression with robust standard errors.ResultsAmong 1120 HIV-infected youth who were ART naive at baseline, 805 remained alive and community residents after 3 years. Of these, 270 (33.5%) named at least one baseline HIV-infected contact; 70% (569/805) subsequently initiated ART. Youth with ≥1 HIV-infected same-age baseline contact were more likely to initiate ART [adjusted odds ratio (aOR), 2.95; 95% confidence interval (CI): 1.49 to 5.86] than those with no HIV-infected contact, particularly if the contact was a strong tie (named in >1 domain; aOR, 5.33; 95% CI: 3.34 to 8.52). When nonhousehold contacts were excluded, having an HIV-infected same age contact who was a strong tie remained associated with ART initiation (aOR, 2.81; 95% CI: 1.76 to 4.49).ConclusionsInterventions that increase and strengthen existing social connections to other HIV-infected peers at the time of HIV diagnosis may increase ART initiation among HIV-infected youth.
| S-EPMC7793612 | biostudies-literature
Project description:BACKGROUND:While extensive research has explored pharmacokinetic interactions between antiretroviral therapy and hormonal contraception, few studies have examined whether these interactions affect clinical outcomes. To address this gap, we conducted a systematic review of the literature that describes hormonal contraceptive among HIV infected women who also antiretroviral therapy, focusing on papers that address clinically important outcomes such as pregnancy or ovulation. METHODS:An electronic literature search was conducted of PUBMED and OVID to identify all articles that addressed hormonal contraception co-administered with antiretroviral therapy published in English between 01 January 1990 and 30 October 2014. In addition, manual reference checks of all articles of interest were conducted to identify articles not captured in the electronic search. Our search criteria identified 405 records. The title and abstract of data reports retrieved via the search were reviewed to identify potential articles of interest. Those with any indication of the main outcomes of interest were considered for inclusion (N=162). Abstracts were then reviewed to identify those manuscripts that would merit a review of the full text version (N=64). Eight articles that addressed the outcomes of interest were identified. The Newcastle-Ottawa Scale was used to assess the quality of these articles. RESULTS:The studies reviewed were limited in a number of ways that precluded their providing a rigorous assessment of the efficacy of contraception when co-administered with antiretroviral therapy. DISCUSSION:None of the studies were of adequate quality to provide the guidance that providers and HIV infected women need when considering contraceptive options. High quality, well-powered studies are required to address the efficacy of hormonal contraception when co-administered with antiretroviral therapy.
| S-EPMC5611808 | biostudies-literature
Project description:BackgroundLevonorgestrel subdermal implants are preferred contraceptives with an expected failure rate of <1% over 5 years. We assessed the effect of efavirenz- or nevirapine-based antiretroviral therapy (ART) coadministration on levonorgestrel pharmacokinetics.MethodsThis nonrandomized, parallel group, pharmacokinetic evaluation was conducted in three groups of human immunodeficiency virus-infected Ugandan women: ART-naive (n = 17), efavirenz-based ART (n = 20), and nevirapine-based ART (n = 20). Levonorgestrel implants were inserted at baseline in all women. Blood was collected at 1, 4, 12, 24, 36, and 48 weeks. The primary endpoint was week 24 levonorgestrel concentrations, compared between the ART-naive group and each ART group by geometric mean ratio (GMR) with 90% confidence interval (CI). Secondary endpoints included week 48 levonorgestrel concentrations and unintended pregnancies.ResultsWeek 24 geometric mean levonorgestrel concentrations were 528, 280, and 710 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.53; 90% CI, .50, .55 and nevirapine: ART-naive GMR, 1.35; 90% CI, 1.29, 1.43). Week 48 levonorgestrel concentrations were 580, 247, and 664 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.43; 90% CI, .42, .44 and nevirapine: ART-naive GMR, 1.14; 90% CI, 1.14, 1.16). Three pregnancies (3/20, 15%) occurred in the efavirenz group between weeks 36 and 48. No pregnancies occurred in the ART-naive or nevirapine groups.ConclusionsWithin 1 year of combined use, levonorgestrel exposure was markedly reduced in participants who received efavirenz-based ART, accompanied by contraceptive failures. In contrast, nevirapine-based ART did not adversely affect levonorgestrel exposure or efficacy.Clinical trials registrationNCT01789879.
| S-EPMC4772838 | biostudies-literature
Project description:The primary objective of this study was to characterize the pharmacokinetics of etonogestrel (ENG) released from a contraceptive implant in Ugandan women living with HIV who were receiving efavirenz (EFV) or nevirapine (NVP)-based antiretroviral therapy (ART), compared with ART-naive women over 24 weeks.Nonrandomized, parallel-group study with three arms: ART-naive, NVP, or EFV-based ART (N?=?20/group).Sparse pharmacokinetic sampling of ENG, NVP, or EFV were performed at screening, entry, and then 1, 4, 12, and 24-week postimplant insertion. The primary endpoint was ENG concentrations at week 24, compared between the ART-naive group and each ART group, using geometric mean ratio (GMR) with 90% confidence intervals.Sixty participants competed the 24-week study and data from 58 participants are included; one participant each was excluded from the NVP group and EFV group because of a sample processing error and ART nonadherence, respectively. At week 24, geometric mean ENG was 362, 341, and 66?pg/ml in the ART-naive, NVP, and EFV groups, respectively [GMR: NVP?:?ART-naive 0.94 (0.90-1.01); EFV?:?ART-naive 0.18 (0.17-0.20)]. NVP and EFV concentrations were lower at week 24 compared to preimplant [NVP: geometric mean 5.7 versus 6.8?mg/l, respectively, GMR 0.84 (0.83-0.85); EFV: geometric mean 3.6 versus 4.9?mg/l, respectively, GMR 0.73 (0.69-0.80)].After 24 weeks of combined use, ENG exposure was 82% lower in women using EFV-based ART compared with ART-naive women. In contrast, NVP did not significantly impact ENG exposure. These results raise concerns about reduced effectiveness of implantable contraception for women taking EFV-based ART.
| S-EPMC5578871 | biostudies-literature
Project description:BackgroundUse of long-acting, highly effective contraception has the potential to improve women's ability to avoid short interpregnancy intervals, which are associated with an increased risk of maternal morbidity and mortality, and preterm delivery. In Uganda, contraceptive implants are not routinely available during the immediate postpartum period.ObjectiveThe purpose of this study was to compare the proportion of women using levonorgestrel contraceptive implants at 6 months after delivery in women randomized to immediate or delayed insertion.Study designThis was a randomized controlled trial among women in Kampala, Uganda. Women who desired contraceptive implants were randomly assigned to insertion of a 2-rod contraceptive implant system containing 75 mg of levonorgestrel immediately following delivery (within 5 days of delivery and before discharge from the hospital) or delayed insertion (6 weeks postpartum). The primary outcome was implant utilization at 6 months postpartum.ResultsFrom June to October 2015, 205 women were randomized, 103 to the immediate group and 102 to the delayed group. Ninety-three percent completed the 6 month follow-up visit. At 6 months, implant use was higher in the immediate group compared with the delayed group (97% vs 68%; P < .001), as was the use of any highly effective contraceptive (98% vs 81%; P = .001). Women in the immediate group were more satisfied with the timing of implant placement. If given the choice, 81% of women in the immediate group and 63% of women in the delayed group would choose the same timing of placement again (P = .01). There were no serious adverse events in either group.ConclusionOffering women the option of initiating contraceptive implants in the immediate postpartum period has the potential to increase contraceptive utilization, decrease unwanted pregnancies, prevent short interpregnancy intervals, and help women achieve their reproductive goals.
| S-EPMC6310612 | biostudies-literature
Project description:Among HIV-infected women, perinatal depression compromises clinical, maternal, and child health outcomes. Antiretroviral therapy (ART) is associated with lower depression symptom severity but the uniformity of effect through pregnancy and postpartum periods is unknown.We analyzed prospective data from 447 HIV-infected women (18-49 years) initiating ART in rural Uganda (2005-2012). Participants completed blood work and comprehensive questionnaires quarterly. Pregnancy status was assessed by self-report. Analysis time periods were defined as currently pregnant, postpartum (0-12 months post-pregnancy outcome), or non-pregnancy-related. Depression symptom severity was measured using a modified Hopkins Symptom Checklist 15, with scores ranging from 1 to 4. Probable depression was defined as >1.75. Linear regression with generalized estimating equations was used to compare mean depression scores over the 3 periods.At enrollment, median age was 32 years (interquartile range: 27-37), median CD4 count was 160 cells per cubic millimeter (interquartile range: 95-245), and mean depression score was 1.75 (s = 0.58) (39% with probable depression). Over 4.1 median years of follow-up, 104 women experienced 151 pregnancies. Mean depression scores did not differ across the time periods (P = 0.75). Multivariable models yielded similar findings. Increasing time on ART, viral suppression, better physical health, and "never married" were independently associated with lower mean depression scores. Findings were consistent when assessing probable depression.Although the lack of association between depression and perinatal periods is reassuring, high depression prevalence at treatment initiation and continued incidence across pregnancy and non-pregnancy-related periods of follow-up highlight the critical need for mental health services for HIV-infected women to optimize both maternal and perinatal health.
| S-EPMC4251908 | biostudies-literature