Long-Term Virological Treatment Outcomes in Adolescents and Young Adults With Perinatally and Non-Perinatally Acquired Human Immunodeficiency Virus.

Background: Long-term viral suppression on antiretroviral therapy (ART) is not established among all people with human immunodeficiency virus (PWH). Young adults (18-24 years) are recognized as a group vulnerable for suboptimal virological treatment outcomes. The aim of this study is to evaluate longitudinal virological treatment outcomes and to identify risk factors for virological failure (VF) among young adults with non-perinatally and perinatally acquired human immunodeficiency virus (HIV) in the Netherlands. Methods: We included individuals registered in the national ATHENA observational cohort from 2000 until 2020 who had entered care before the age of 25 years, who had received ART for at least 6 months with at least 2 available HIV ribonucleic acid measurements between the age of 18 and 24 years. We compared VF between age groups 12-17, 18-24, and 25-30 years. A multivariable generalized linear mixed model was used to evaluate risk factors for VF. Analyses were stratified by HIV acquisition mode. Results: In total, 1174 non-perinatally PWH and 157 perinatally PWH were included. In 2020, VF rate was 7% in non-perinatally PWH young adults and 19% in perinatally PWH young adults. The adjusted risk for VF was significantly higher in those aged 18-24 compared to 25-30 years in both non-perinatally PWH (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.07-1.50) and perinatally PWH (OR, 2.34; 95% CI, 1.48-3.71). Conclusions: Young adulthood is a vulnerable period, with increased risk for VF, especially for perinatally PWH. The probability of VF decreased over time, but less for perinatally PWH compared to non-perinatally PWH.

Preconception use of cART by HIV-positive pregnant women increases the risk of infants being born small for gestational age.

BACKGROUND: The benefits of combination anti-retroviral therapy (cART) in HIV-positive pregnant women (improved maternal health and prevention of mother to child transmission [pMTCT]) currently outweigh the adverse effects due to cART. As the variety of cART increases, however, the question arises as to which type of cART is safest for pregnant women and women of childbearing age. We studied the effect of timing and exposure to different classes of cART on adverse birth outcomes in a large HIV cohort in the Netherlands. MATERIALS AND METHODS: We included singleton HEU infants registered in the ATHENA cohort from 1997 to 2015. Multivariate logistic regression analysis for single and multiple pregnancies was used to evaluate predictors of small for gestational age (SGA, birth weight <10th percentile for gestational age), low birth weight and preterm delivery. RESULTS: A total of 1392 children born to 1022 mothers were included. Of these, 331 (23.8%) children were SGA. Women starting cART before conception had an increased risk of having a SGA infant compared to women starting cART after conception (OR 1.35, 95% CI 1.03-1.77, p = 0.03). The risk for SGA was highest in women who started a protease inhibitor-(PI) based regimen prior to pregnancy, compared with women who initiated PI-based cART during pregnancy. While the association of preterm delivery and preconception cART was significant in univariate analysis, on multivariate analysis only a non-significant trend was observed (OR 1.39, 95% CI 0.94-1.92, p = 0.06) in women who had started cART before compared to after conception. In multivariate analysis, the risk of low birth weight (OR 1.34, 95% CI 0.94-1.92, p = 0.11) was not significantly increased in women who had started cART prior to conception compared to after conception. CONCLUSION: In our cohort of pregnant HIV-positive women, the use of cART prior to conception, most notably a PI-based regimen, was associated with intrauterine growth restriction resulting in SGA. Data showed a non-significant trend in the risk of PTD associated with preconception use of cART compared to its use after conception. More studies are needed with regard to the mechanisms taking place in the placenta during fetal growth in pregnant HIV-positive women using cART. It will only be with this knowledge that we can begin to understand the potential impact of HIV and cART on the fetus, in order to be able to determine the optimal individualised drug regimen for HIV-infected women of childbearing age.

Hcv coinfection, an important risk factor for hepatotoxicity in pregnant women starting antiretroviral therapy.

OBJECTIVES: This retrospective cohort study evaluated the risk of hepatotoxicity in HIV-1 positive pregnant and non-pregnant women starting combined ART. METHODS: Data were used from the ATHENA observational cohort. The study population consisted of HIV-1 infected, therapy naïve, pregnant and non-pregnant women, followed between January 1997 and February 2008. Demographic, treatment and pregnancy related data were collected. Risk of hepatotoxicity was determined using univariate and multivariate logistic regression. Analyses were adjusted for age, region of origin, baseline HIV-RNA levels and CD4 cell counts, cART regimen and hepatitis B and C coinfection. ALT and AST values of more than 5 times ULN were considered as hepatotoxicity. RESULTS: Four-hundred and twenty-five pregnant and 1121 non-pregnant women were included. Independent risk factors of hepatotoxicity in all women were the presence of detectable HCV RNA (OR 5.48, 95% CI 2.25-13.38, p<0.001) and NVP use (OR 2.63, 95% CI 1.54-4.55, p<0.001). Stratified for pregnancy, the adjusted risk of hepatotoxicity was significantly associated with HCV coinfection only during pregnancy (OR 23.53, 95% CI 4.69-118.01, p<0.001). NVP use is related to hepatotoxicity in pregnant (OR 5.26, 95% CI 1.61-16.67, p<0.005) as well as in non-pregnant women (OR 2.13, 95% CI 1.11-4.00, p=0.02). CONCLUSION: HCV coinfection and NVP use are associated with a higher risk of cART induced hepatotoxicity in pregnant women.

HIV status disclosure among HIV-positive African and Afro-Caribbean people in the Netherlands.

HIV status disclosure is often characterized as a dilemma. On the one hand, disclosure can promote health, social support, and psychological well-being. On the other, disclosure can lead to stigmatization, rejection, and other negative social interactions. Previous research has shown that HIV status disclosure is a reasoned process whereby the costs and benefits to oneself and to others are weighed. As such, understanding disclosure requires understanding the reasons for and against disclosure employed by people living with HIV (PLWH). In this study, disclosure among a population disproportionately affected by HIV in the Netherlands, namely African and Afro-Caribbean diaspora, was investigated. Reasons for nondisclosure were fear of stigmatization, previous negative experiences with disclosure, having observed the stigmatization of other PLWH, shame, the desire to protect others - particularly one's children and family - from stigmatization by association and/or worrying, and the belief that one's HIV status is a private matter. Participants reported disclosing because they were in a close and supportive relationship, disclosure led to emotional release, disclosure could lead to emotional or financial support, they felt a perceived duty to inform, and they had a desire to educate others about sexual risk-taking. The findings suggest that stigma plays an important role in disclosure decisions among these populations. They further point to a need for HIV-related stigma reduction interventions in African and Afro-Caribbean communities and culturally sensitive counseling for PLWH whereby caregivers do not automatically assume that disclosure is best but rather provide a safe environment in which the costs and benefits of disclosure can be weighed and strategies for disclosure can be developed, if perceived as beneficial by PLWH.

Which method of adherence measurement is most suitable for daily use to predict virological failure among immigrant and non-immigrant HIV-1 infected patients?

In industrialized countries, virological failure occurs more often among HIV-infected immigrant patients. Non-adherence is the most credible explanation. We compared adherence of immigrant patients with that of non-immigrant patients in the Netherlands, and investigated which method of adherence measurement is most suitable for daily use to predict virological treatment failure: testing knowledge of the current regimen, a quantitative adherence interview, pharmacy prescription refill ratio (dispensed medication divided by prescribed medication, DM/PM), and plasma drug levels. Included were 61 immigrants and 81 non-immigrants. Virological failure did occur more often in immigrants than in non-immigrants (19.7% (12/61) versus 8.6% (7/81), p=0.056), especially among previously naive patients (19.6% (11/56) versus 0% (0/54), p<0.01). There were no differences between both groups on any of the four adherence measures. Virological failure was associated with reporting stopping medication when not feeling well (OR=12, 95%CI=1.9-77.7, p=0.02), and, among naive patients, also with a DM/PM < 0.85 (Odds Ratio=5.1, 95%Confidence Interval=1.2-22.3, p=0.03). Although our study confirmed a much higher virological failure rate among immigrants, we were unable to identify clear differences in adherence between immigrants and non-immigrant patient, although virological failure was associated with stopping medication when not feeling well and a low DM/PM. Unstructured treatment interruptions are a likely explanation of the findings. Interventions should be aimed at preventing patients to stop medication. A DM/PM below 0.85 can be indicative for patients who did stop medication and are at risk for virological failure.

Nelfinavir plasma concentrations are low during pregnancy.

Plasma nelfinavir concentration ratios (CRs) were calculated for all pregnant (n=27) and nonpregnant (n=48) human immunodeficiency virus type 1-infected women receiving the drug who visited our outpatient clinic. In pregnant women, mean and median nelfinavir CRs were significantly lower (P=.02 and P=.04, respectively), and 51% of the CRs were below the clinically relevant threshold of 0.90, compared with 35% of the CRs in nonpregnant women. After we adjusted for confounders, we found that the mean nelfinavir CR was 34% lower in pregnant women (P=.02). With targeted interventions, subsequent CRs in pregnant women showed a significant increase (median increase, 0.31; P=.01).

Race is not associated with nevirapine pharmacokinetics.

The effect of race on the pharmacokinetics of nevirapine was investigated in a nonselected population. Included patients were ambulatory HIV-1-infected patients from the outpatient clinics of the Academic Medical Center and the Slotervaart Hospital, Amsterdam, The Netherlands. All patients were using nevirapine as part of their antiretroviral regimen and had at least one plasma concentration available for analysis. From the included patients, gender, age, race, hepatitis C status, baseline ASAT value, and body weight were obtained. The nonlinear mixed-effect modeling program (NONMEM) version V 1.1 was used for all analyses. Population pharmacokinetic parameters [clearance (CL/F), volume of distribution (V/F), absorption rate constant (ka)] and interindividual (IIV) and interoccasion variability (IOV) were estimated. The influence of race on the CL/F of nevirapine was tested as Negroid race versus the other races, Asian race versus the other races, and the Negroid and the Asian races as separate variables versus the Caucasian race. A database of 1732 nevirapine plasma concentrations of 383 HIV-1-infected individuals collected during 1186 outpatient clinic visits was available for this analysis. The conclusion of this study is that race is not associated with the pharmacokinetics of nevirapine, and thus requires no dose adaptations.