Antiretroviral Therapy In Women Research Articles

Rates of adverse events of antiretroviral therapy in women living with HIV/AIDS: a systematic review and meta-analysis

ObjectiveThere is limited information regarding the incidence of treatment-related adverse events (AE) following antiretroviral therapy (ART) in women. So, this review aimed to describe the incidence of AE of ART...

Sexual violence and antiretroviral adherence among women of reproductive age in African population-based surveys: the moderating role of the perinatal phase.

Women face challenges in antiretroviral therapy (ART) adherence and achieving viral suppression despite progress in the expansion of HIV treatment. Evidence suggests that violence against women (VAW) is an important determinant of poor ART adherence in women living with HIV (WLH). In our study, we examine the association of sexual VAW and ART adherence among WLH and assess whether this association varies by whether women are pregnant/breastfeeding or not. A pooled analysis was conducted among WLH from Population-Based HIV Impact Assessment cross-sectional surveys (2015-2018) from nine sub-Saharan African countries. Logistic regression was used to examine the association between lifetime sexual violence and suboptimal ART adherence (≥1 missed day in the past 30 days) among reproductive age WLH on ART, and to assess whether there was any evidence for interaction by pregnancy/breastfeeding status, after adjusting for key confounders. A total of 5038 WLH on ART were included. Among all included women, the prevalence of sexual violence was 15.2% (95% confidence interval [CI]: 13.3%-17.1%) and the prevalence of suboptimal ART adherence was 19.8% (95% CI: 18.1%-21.5%). Among only pregnant and breastfeeding women, the prevalence of sexual violence was 13.1% (95% CI: 9.5%-16.8%) and the prevalence of suboptimal ART adherence was 20.1% (95% CI: 15.7%-24.5%). Among all included women, there was evidence for an association between sexual violence and suboptimal ART adherence (adjusted odds ratio [aOR]: 1.69, 95% CI: 1.25-2.28). There was evidence that the association between sexual violence and ART adherence varied by pregnant/breastfeeding status (p = 0.004). Pregnant and breastfeeding women with a history of sexual violence had higher odds of suboptimal ART adherence (aOR: 4.11, 95% CI: 2.13-7.92) compared to pregnant and breastfeeding women without a history of sexual violence, while among non-pregnant and non-breastfeeding women, this association was attenuated (aOR: 1.39, 95% CI: 1.00-1.93). Sexual violence is associated with women's suboptimal ART adherence in sub-Saharan Africa, with a greater effect among pregnant and breastfeeding WLH. To improve women's HIV outcomes and to achieve the elimination of vertical transmission of HIV, violence prevention efforts within maternity services and HIV care and treatment should be a policy priority.

Supporting Treatment for Anti-Retroviral Therapy (START) Together: Protocol for a pilot, randomized, couple-based intervention to promote women's ART adherence and men's engagement in HIV care in KwaZulu-Natal, South Africa

BackgroundSouth Africa currently has the greatest number of people with HIV globally. The country has not yet met its 95-95-95 goals, with different gaps in the HIV care cascade for women and men. This paper reports on a protocol to pilot test a couple-based intervention designed to improve women's antiretroviral therapy (ART) adherence and men's engagement in care in heterosexual couples living in the Vulindlela area of KwaZulu-Natal, South Africa. Study goals are two-fold: (1) assess the acceptability, feasibility, and fidelity of the experimental intervention, START Together, and (2) collect efficacy data on START Together for women's ART adherence, men's engagement in HIV care, and the couple's relationship functioning. MethodsWomen (N = 20) who were not engaged with ART adherence (defined via self-reported ART difficulties, record of missed clinic visits, or viral non-suppression) are the target patients; male partners are not required to know or disclose their HIV status to be part of the study. Couples are randomized 1:1 to the experimental treatment (START Together) or treatment as usual (referrals to the local clinic to support ART adherence or any other HIV-related care). START Together is a 5-session intervention based in cognitive-behavioral couple therapy, which is a skill-based intervention focusing on communication and problem-solving skills, and Life Steps, a problem-solving intervention identifying barriers and solutions to medication adherence. Couples are assessed at baseline, post-treatment (8 weeks post-randomization), and follow-up (12 weeks post-randomization). ConclusionThis study will provide preliminary implementation and efficacy data on whether this novel approach has potential to improve women and men's HIV and healthcare-related needs.

“It’s only fatness, it doesn’t kill”: a qualitative study on perceptions of weight gain from use of dolutegravir-based regimens in women living with HIV in Uganda

BackgroundDolutegravir (DTG)-based regimens have been recommended by the WHO as the preferred first-line and second-line HIV treatment in all populations. Evidence suggests an association with weight gain, particularly among black women. Our study investigated perceptions of weight gain from DTG-based regimen use on body image and adherence of antiretroviral therapy in women living with HIV (WLHIV) in Uganda.MethodsBetween April and June 2021, we conducted semi-structured interviews involving 25 WLHIV (adolescents, women of reproductive potential and post-menopausal women) and 19 healthcare professionals (clinicians, nurses, ART managers and counsellors) purposively selected from HIV clinics in Kampala. The interviews explored perceptions of body weight and image; experiences and management of weight related side effects associated with DTG; and knowledge and communication of DTG-related risks. Data was analysed thematically in NVivo 12 software.ResultsOur findings indicate WLHIV in Uganda commonly disliked thin body size and aspired to gain moderate to high level body weight to improve their body image, social standing and hide their sero-positive status. Both WLHIV and healthcare professionals widely associated weight gain with DTG use, although it was rarely perceived as an adverse event and was unlikely to be reported or to alter medication adherence. Clinical management and pharmacovigilance of DTG-related weight gain were hampered by the limited knowledge of WLHIV of the health risks of being over-weight and obesity; lack of diagnostic equipment and resources; and limited clinical guidance for managing weight gain and associated cardiovascular and metabolic comorbidities.ConclusionsThe study highlights the significance of large body-size in promoting psychosocial wellbeing in WLHIV in Uganda. Although weight gain is recognized as a side effect of DTG, it may be welcomed by some WLHIV. Healthcare professionals should actively talk about and monitor for weight gain and occurrence of associated comorbidities to facilitate timely interventions. Improved supply of diagnostic equipment and support with sufficient guidance for managing weight gain for healthcare professionals in Uganda are recommended.

Childbearing desire and reproductive behaviors among women living with HIV: A cross-sectional study in Abidjan, Côte d'Ivoire.

IntroductionEvidence on childbearing desire and reproductive behaviors in women living with HIV on antiretroviral therapy (ART) is scarce, particularly in West Africa. We investigated the prevalence and associated factors of childbearing desire in HIV-infected women in care in Abidjan, Côte d’Ivoire and explored whether such desires were translated into behaviors related to contraceptive use and communication with health personnel.MethodsA cross-sectional survey was conducted in two HIV-care facilities in Abidjan, Côte d’Ivoire in 2015. Eligible women were non-pregnant, non-menopausal, aged 18–49 years and diagnosed as HIV-infected. The outcomes were childbearing desire, prevalence of modern contraceptive use, unmet needs for family planning and intention of the last pregnancy since HIV diagnosis. Women wishing to conceive immediately were asked whether they had discussed their desire with HIV healthcare workers. Logistic regression models were used to assess the associations between the outcomes and women’s characteristics.ResultsOf 1,631 women, 80% declared having childbearing desire. No association was found between women’s childbearing desire and ART status or its duration. In multivariate models, younger age, being in a stable relationship and having no or only one child were significantly associated with increased childbearing desire. Of the women wishing to conceive immediately (n = 713), only 43% reported having had fertility-related dialogue with healthcare provider. Among sexually active women wanting to avoid or delay pregnancy (n = 650), unmet needs for family planning was 40%. Regarding the last pregnancy since HIV diagnosis, one in three women reported not having wanted a baby at that time.ConclusionsPregnancy desire in women living with HIV in Abidjan was extremely high. Integration of safe conception strategies as well as improvement of contraceptive uptake among women in need of family planning are of utmost importance to ensure optimal conception and to avoid transmission of HIV to the male partner or to the forthcoming child.

“I feel empowered”: women’s perspectives on and experiences with long-acting injectable antiretroviral therapy in the USA and Spain

Long-acting injectable antiretroviral therapy has been shown to be non-inferior to daily oral antiretroviral therapy in clinical trials and may soon become part of clinical care. While most trial participants to date have been men, approximately one quarter of ongoing Phase 3 trial participants are women offering an important opportunity to understand how long-acting antiretroviral therapy is perceived and experienced by women. We conducted in-depth interviews with 80 people living with HIV participating in Phase 2 and 3 clinical trials of long-acting antiretroviral therapy in the USA and Spain. Fifteen percent (12/80) of trial participants interviewed were women. Interviews were audio-recorded, transcribed and coded using content analysis, focused on gender-specific themes. Women shared many of the positive perceptions expressed by men but also had unique perspectives, including finding that long-acting antiretroviral therapy addressed the challenge of remembering pills amidst busy day-to-day realities including multiple roles and responsibilities, is less time consuming and creates less stress compared to oral antiretroviral therapy, and is emotionally freeing and empowering. The gendered nature of women’s lives shaped why and how they were satisfied with long-acting antiretroviral therapy. Findings can inform interventions and support systems to facilitate uptake of and adherence to long-acting antiretroviral therapy in women.

The antagonism of folate receptor by dolutegravir: developmental toxicity reduction by supplemental folic acid.

Maternal folate (vitamin B9) status is the largest known modifier of neural tube defect risk, so we evaluated folate-related mechanisms of action for dolutegravir (DTG) developmental toxicity. Folate receptor 1 (FOLR1) was examined as a target for DTG developmental toxicity using protein and cellular interaction studies and an animal model. FOLR1 competitive binding studies were used to test DTG for FOLR1 antagonism. Human placenta cell line studies were used to test interactions with DTG, folate, and cations. Zebrafish were selected as an animal model to examine DTG-induced developmental toxicity and rescue strategies. FOLR1 binding studies indicate DTG is a noncompetitive FOLR1 antagonist at therapeutic concentrations. In-vitro testing indicates calcium (2 mmol/l) increases FOLR1-folate interactions and alters DTG-FOLR1-folate interactions and cytotoxicity. DTG does not inhibit downstream folate metabolism by dihydrofolate reductase. Early embryonic exposure to DTG is developmentally toxic in zebrafish, and supplemental folic acid can mitigate DTG developmental toxicity. Folates and FOLR1 are established modifiers of risk for neural tube defects, and binding data indicates DTG is a partial antagonist of FOLR1. Supplemental folate can ameliorate increased developmental toxicity due to DTG in zebrafish. The results from these studies are expected to inform and guide future animal models and clinical studies of DTG-based antiretroviral therapy in women of childbearing age.

The relationship between HIV stigma and adherence to antiretroviral (ARV) drug therapy among women with HIV in Lampung, Indonesia

The aim of our study was to examine the relationship between HIV stigma and adherence to antiretroviral (ARV) therapy among women with HIV. 120 women with HIV involved in this cross-sectional study. The participant were outpatients at the Voluntary Counseling and Testing (VCT) Abdul Moeloek Hospital in Lampung, Indonesia. We examined data from 120 patients. Through chi-squared tests, a statistically significant correlation between HIV stigma and adherence to ARV therapy was revealed (p-value=0.045; OR 2.274) women with low levels of stigma toward HIV demonstrated adherence to ARV treatment that was 2.27 times greater than that of women with high levels of stigma toward HIV. One way to increase adherence to ARV therapy in women with HIV is by minimizing its stigma. This can be done by increasing their self-confidence and not differentiating between people living with HIV and others in the provision of health services.

A Text Messaging Intervention to Support Option B+ in Kenya: A Qualitative Study

Key challenges in providing lifelong antiretroviral therapy (ART) to pregnant and breastfeeding women (Option B+) in sub-Saharan Africa include achieving long-term adherence and retention in care. One intervention that may help address these challenges is mobile text messaging. We evaluated the acceptability of a text messaging intervention to support women's ART adherence and retention in care in rural western Kenya. Forty in-depth interviews with 20 pregnant/postpartum women infected with HIV, their male partners, and four focus groups with 30 health care providers were conducted during September-November 2014. Data were coded and analyzed using thematic analysis. Findings revealed the following themes: (a) overall acceptability of the text messaging intervention; (b) proposed content of text messages; (c) format, timing, and language of text messages; and (d) potential challenges of the text messaging intervention. Findings were used to refine a text messaging intervention being evaluated at Kenyan study sites rolling out Option B+.

Does telephone intervention affect adherence to antiretroviral therapy in women with human immunodeficiency virus

Objective: to evaluate the impact of a telephone intervention on the adherence to antiretroviral therapy in women with human immunodeficiency virus. Methods: quasi experimental study, before and after, conducted ina specialized service with 19 women who live with the human immunodeficiency virus. The study was developedin four phases: recruitment; assessment of adherence to antiretroviral treatment, telephone intervention and reassessment of adherence. During three months of follow-up, eight calls were made to each participant, totaling 152 interventions. Results: there was a statistically significant improvement in the number of participants with adequate adherence (p=0.004) and in the mean of adherence scores (p=0.000) after the intervention. There was no significant impact on the immune status. Conclusion: telephone interventions aimed at women with human immunodeficiency virus developed during three months proved to be effective for improving adherenceto treatment.

Continuous quality improvement interventions to improve long-term outcomes of antiretroviral therapy in women who initiated therapy during pregnancy or breastfeeding in the Democratic Republic of Congo: design of an open-label, parallel, group randomized trial

Continuous quality improvement interventions to improve long-term outcomes of antiretroviral therapy in women who initiated therapy during pregnancy or breastfeeding in the Democratic Republic of Congo: design of an open-label, parallel, group randomized trial

Continuous quality improvement interventions to improve long-term outcomes of antiretroviral therapy in women who initiated therapy during pregnancy or breastfeeding in the Democratic Republic of Congo: design of an open-label, parallel, group randomized trial

BackgroundDespite the rapid adoption of the World Health Organization’s 2013 guidelines, children continue to be infected with HIV perinatally because of sub-optimal adherence to the continuum of HIV care in maternal and child health (MCH) clinics. To achieve the UNAIDS goal of eliminating mother-to-child HIV transmission, multiple, adaptive interventions need to be implemented to improve adherence to the HIV continuum.MethodsThe aim of this open label, parallel, group randomized trial is to evaluate the effectiveness of Continuous Quality Improvement (CQI) interventions implemented at facility and health district levels to improve retention in care and virological suppression through 24 months postpartum among pregnant and breastfeeding women receiving ART in MCH clinics in Kinshasa, Democratic Republic of Congo. Prior to randomization, the current monitoring and evaluation system will be strengthened to enable collection of high quality individual patient-level data necessary for timely indicators production and program outcomes monitoring to inform CQI interventions. Following randomization, in health districts randomized to CQI, quality improvement (QI) teams will be established at the district level and at MCH clinics level. For 18 months, QI teams will be brought together quarterly to identify key bottlenecks in the care delivery system using data from the monitoring system, develop an action plan to address those bottlenecks, and implement the action plan at the level of their district or clinics.DiscussionIf proven to be effective, CQI as designed here, could be scaled up rapidly in resource-scarce settings to accelerate progress towards the goal of an AIDS free generation.Trial registrationThe protocol was retrospectively registered on February 7, 2017. ClinicalTrials.gov Identifier: NCT03048669.

Understanding Antiretroviral Treatment Adherence Among HIV-Positive Women at Four Postpartum Time Intervals: Qualitative Results from the Kabeho Study in Rwanda.

As lifelong antiretroviral therapy (ART) for pregnant women is implemented, it is important to understand the attitudes and norms affecting women's postpartum ART adherence. This is a qualitative cross-sectional study of HIV-positive postpartum women (n = 112) enrolled in a 2-year observational prospective cohort in Rwanda. Informed by the Theory of Reasoned Action (TRA), we conducted in-depth interviews with women whose children were 0-6, 7-12, 13-18, or 21-24 months of age to describe factors contributing to adherence and changes over time. Positive ART attitudes reported by women included mothers' health promotion, prevention of infant HIV infection, higher CD4 count, and improved physical appearance. Negative attitudes were few, but included side effects and the lifelong nature of treatment. Learning from people living with HIV (PLHIV) was identified as a norm facilitating adherence; ART adherence was inhibited by fear of disclosure or stigmatization in communities and clinics. Poor adherence behaviors were common immediately after HIV diagnosis, not necessarily during prevention of mother-to-child transmission (PMTCT). Women with older children, most of whom stopped breastfeeding by 13-18 months, reported more barriers and missed doses than women with younger children. The TRA was useful in identifying the collective influence of attitudes, norms, and intentions on behavior. Findings suggest that HIV-positive women are vulnerable to poor adherence following HIV diagnosis and around the time of breastfeeding cessation. Lifelong treatment adherence can be supported through PLHIV exemplifying long-term ART use, fewer and less stigmatizing clinic visits, and counseling messages highlighting the benefits of drugs on appearance and illness prevention and incorporating biological feedback.

The adherence gap: a longitudinal examination of men's and women's antiretroviral therapy adherence in British Columbia, 2000-2014.

The aim of this study was to observe the effect of sex on attaining optimal adherence to combination antiretroviral therapy (cART) longitudinally while controlling for known adherence confounders - IDU and ethnicity. Using the population-based HAART Observational Medical Evaluation and Research cohort, data were collected from HIV-positive adults, aged at least 19 years, receiving cART in British Columbia, Canada, with data collected between 2000 and 2014. cART adherence was assessed using pharmacy refill data. The proportion of participants reaching optimal (≥95%) adherence by sex was compared per 6-month period from initiation of therapy onward. Generalized linear mixed models with logistic regression examined the effect of sex on cART adherence. Among 4534 individuals followed for a median of 65.9 months (interquartile range: 37.0-103.2), 904 (19.9%) were women, 589 (13.0%) were Indigenous, and 1603 (35.4%) had a history of IDU. A significantly lower proportion of women relative to men were optimally adherent overall (57.0 vs. 77.1%; P < 0.001) and in covariate analyses. In adjusted analyses, female sex remained independently associated with suboptimal adherence overall (adjusted odds ratio: 0.55; 95% confidence interval: 0.48-0.63). Women living with HIV had significantly lower cART adherence rates then men across a 14-year period overall, and by subgroup. Targeted research is required to identify barriers to adherence among women living with HIV to tailor women-centered HIV care and treatment support services.

Psychosocial Aspects of ART Counseling: A Comparison of HIV Beliefs and Knowledge in PMTCT and ART-Naïve Women

Antiretroviral therapy (ART)-readiness counseling has been deemed critical to adherence, instilling knowledge, and promoting positive beliefs and attitudes. In the landscape of changing policy in South Africa, some ART initiators have had prior ART-readiness counseling (e.g., for prevention-of-mother-to-child-transmission [PMTCT] programs). The extent to which previous counseling resulted in retained knowledge and belief is unknown, which may be important to the promotion of women's ART adherence. We compared 320 women living with HIV and initiating ART, with and without prior PMTCT on HIV knowledge, treatment, beliefs, and attitudes. The PMTCT group held more accurate beliefs and more positive attitudes about ART. Both groups lacked understanding of basic HIV biology. Nondisclosure of HIV status was high. Thus, in individuals re-initiating therapy, some knowledge about HIV and its treatment was not well retained. Tailored education and counseling may be critical to adherence, with a focus on biological concepts that impact ART resistance.

Efficacy and safety of tenofovir-containing antiretroviral therapy in women who acquired HIV while enrolled in tenofovir gel prophylaxis trials.

We assessed whether women who acquired HIV during tenofovir gel prophylaxis trials can be safely and effectively treated with tenofovir-containing antiretroviral therapy (ART). Between May 2011 and October 2014, HIV seroconvertors from two tenofovir gel trials were recruited when eligible for ART (CD4+ T-cell count <350 cells/μl, pregnancy or AIDS-defining illness). Women were randomized to tenofovir-containing (tenofovir + lamivudine/emtricitabine + efavirenz) or tenofovir-sparing (zidovudine + lamivudine/emtricitabine + efavirenz) antiretroviral treatment regimens. The proportion with virological suppression, adverse events and drug switches were compared. Fifty-nine women were enrolled and followed-up for median 18 months (IQR 6-24). Twenty-nine women (7 tenofovir gel exposed, 22 tenofovir gel unexposed) were randomized to a tenofovir-containing and 30 (9 tenofovir gel exposed, 21 tenofovir gel unexposed) to a tenofovir-sparing regimen. Median baseline CD4+ T-cell count and viral load (VL) were 345 cells/μl (IQR 280-423) and 4.5 log copies/ml (sd 0.79), and did not differ by ART assignment. Overall VL suppression rates were 88.0% and 78.3% at 6 months (P=0.454) and 85.7% and 79.0% at 12 months (P=0.689) in women on the tenofovir-containing and tenofovir-sparing regimens, respectively. Toxicity-related drug switches were more frequent in women on the tenofovir-sparing than tenofovir-containing regimen (36.7% versus 0.0%, P<0.001). Preliminary data show that tenofovir-containing ART was effective and more tolerable in HIV seroconvertors from tenofovir gel prophylaxis trials and may be considered for use in women with prior tenofovir gel exposure. Clinical trials.gov NCT01387022.

Low-Frequency Nevirapine (NVP)–Resistant HIV-1 Variants Are Not Associated With Failure of Antiretroviral Therapy in Women Without Prior Exposure to Single-Dose NVP

Low-frequency nevirapine (NVP)-resistant variants have been associated with virologic failure (VF) of initial NVP-based combination antiretroviral therapy (cART) in women with prior exposure to single-dose NVP (sdNVP). We investigated whether a similar association exists in women without prior sdNVP exposure. Pre-cART plasma was analyzed by allele-specific polymerase chain reaction to quantify NVP-resistant mutants in human immunodeficiency virus-infected African women without prior sdNVP who were starting first-line NVP-based cART in the OCTANE/A5208 trial 2. Associations between NVP-resistant mutants and VF or death were determined and compared with published results from women participating in the OCTANE/A5208 trial 1 who had taken sdNVP and initiated NVP-based cART. Pre-cART NVP-resistant variants were detected in 18% (39/219) of women without prior sdNVP exposure, compared to 45% (51/114) with prior sdNVP exposure (P < .001). Among women without prior sdNVP exposure, 8 of 39 (21%) with NVP-resistant variants experienced VF or death vs 31 of 180 (17%) without such variants (P = .65); this compares with 21 of 51 (41%) vs 9 of 63 (14%) among women with prior exposure (P = .001). The risk of VF on NVP-based cART from NVP-resistant variants differs between sdNVP-exposed and -unexposed women. This difference may be driven by drug-resistance mutations emerging after sdNVP exposure that are linked on the same viral genome. NCT00089505.

Effectiveness of non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in women previously exposed to a single intrapartum dose of nevirapine: a multi-country, prospective cohort study.

Intrapartum and neonatal single-dose nevirapine (NVP) reduces the risk of mother-to-child HIV transmission but also induces viral resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. This drug resistance largely fades over time. We hypothesized that women with a prior single-dose NVP exposure would have no more than a 10% higher cumulative prevalence of failure of their NNRTI-containing antiretroviral therapy (ART) over the first 48 wk of therapy than would women without a prior exposure. We enrolled 355 NVP-exposed and 523 NVP-unexposed women at two sites in Zambia, one site in Kenya, and two sites in Thailand into a prospective, non-inferiority cohort study and followed them for 48 wk on ART. Those who died, discontinued NNRTI-containing ART, or had a plasma viral load >or=400 copies/ml at either the 24 wk or 48 wk study visits and confirmed on repeat testing were characterized as having failed therapy. Overall, 114 of 355 NVP-exposed women (32.1%) and 132 of 523 NVP-unexposed women (25.2%) met criteria for treatment failure. The difference in failure rates between the exposure groups was 6.9% (95% confidence interval [CI] 0.8%-13.0%). The failure rates of women stratified by our predefined exposure interval categories were as follows: 47 of 116 women in whom less than 6 mo elapsed between exposure and starting ART failed therapy (40%; p<0.001 compared to unexposed women); 25 of 67 women in whom 7-12 mo elapsed between exposure and starting ART failed therapy (37%; p = 0.04 compared to unexposed women); and 42 of 172 women in whom more than 12 mo elapsed between exposure and starting ART failed therapy (24%; p = 0.82 compared to unexposed women). Locally weighted regression analysis also indicated a clear inverse relationship between virologic failure and the exposure interval. Prior exposure to single-dose NVP was associated with an increased risk of treatment failure; however, this risk seems largely confined to women with a more recent exposure. Women requiring ART within 12 mo of NVP exposure should not be prescribed an NNRTI-containing regimen as first-line therapy.

Tenofovir disoproxil fumarate in pregnancy and prevention of mother‐to‐child transmission of HIV‐1: is it time to move on from zidovudine?

Zidovudine (ZDV) has been the cornerstone of antiretroviral (ARV) therapy for pregnant women infected with HIV-1 in the prevention of mother-to-child transmission (MTCT) and remains the only licensed ARV for use in pregnancy. We explored the current and future roles of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT of HIV-1. We reviewed the published literature by conducting database searches of in vitro, animal and clinical studies, reported in journals and at conferences, using the search terms Tenofovir/gs4331/viread, pregnant/pregnancy, lactate, lactation, natal, reproduce/reproduction, placenta/placental, malformation, and teratogenicity/teratogenic. In a macaque model, perinatal exposure to very high dose tenofovir resulted in bone toxicity in some offspring. However, perinatal use of TDF, both single dose and as part of highly active antiretroviral therapy in women, has been well tolerated in the short term by mothers and their infants. Further, the addition of single-dose TDF to single-dose nevirapine (SD-NVP) during delivery following maternal ZDV use during pregnancy significantly reduces the frequency of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance. The addition of TDF to SD-NVP reduces NNRTI resistance. The role of TDF in this setting and during pregnancy for reducing rates of MTCT requires investigation. While short-term toxicity data are encouraging, long-term follow-up of exposed mothers and infants is required.

Plasma Homocysteine Is Not Associated With HIV Serostatus or Antiretroviral Therapy in Women

The effects of HIV serostatus and combination antiretroviral therapy (cART) on plasma homocysteine (HCY) are uncertain. Plasma HCY was assayed in a cross-sectional study of 249 HIV-infected and 127 HIV-uninfected women at the Bronx Women's Interagency HIV Study site. Mean plasma HCY was 7.42 +/- 2.68 in HIV-infected women and 7.18 +/- 2.66 mumol/L in HIV-uninfected women (P = 0.40). Hyperhomocysteinemia (defined as HCY >10 mumol/L) was seen in 16.9% and 13.4% of HIV-infected and HIV-uninfected women, respectively (P = 0.45). Among HIV-infected women, cART use was not associated with HCY level. Compared with the lowest quartile, women with HCY in the highest quartile had lower mean serum vitamin B12 and RBC folate levels. In multivariate analysis that did not include micronutrient levels, age, serum creatinine, and lower CD4% were significantly associated with plasma HCY level in HIV-infected women. Plasma HCY was not associated with HIV serostatus or use of cART in this cross-sectional study. Reduced availability of folate cofactors for HCY remethylation in HIV-infected women with lower folate intake and decreased health status may influence HCY levels.