HIV Antiretroviral Therapy Research Articles

Efficacy and Safety of Dolutegravir With Emtricitabine and Tenofovir Alafenamide Fumarate or Tenofovir Disoproxil Fumarate, and Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate HIV Antiretroviral Therapy Regimens Started in Pregnancy (IMPAACT 2010/VESTED): A Multicentre, Open-label, Randomised, Controlled, Phase 3 Trial

Over 1 million women with HIV-1 become pregnant yearly. The use of antiretroviral therapy (ART) during pregnancy is important for the reduction of perinatal HIV transmission from mother to child and to improve maternal health outcomes. There is limited high quality data on the safety and effectiveness of ART with the use of dolutegravir. Dolutegravir was named a first-line therapy in adults with HIV by the World Health Organization in 2018.This study is a phase 3, multicenter open-label randomized controlled study performed in pregnant women from 14 to 28 weeks' gestation (≥18 years of age) in 9 countries (including the United States, Brazil, South Africa, and India). Women with multiple fetuses, a known fetal anomaly, a known psychiatric illness in the mother, active tuberculosis in the mother, laboratory abnormalities (a Cr clearance <60 mL per minute or alanine aminotransferase or aspartate aminotransferase ≥2.5 the upper limit or normal) or >14 days of ART during the current pregnancy were excluded.Participants were split on the basis of gestational age (14–18 weeks, 19–23 weeks, and 24–28 weeks) and were randomly assigned to receive either: (1) once-daily oral dolutegravir 50 mg (integrase strand transfer inhibitors) plus once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir alafenamide fumarate 25 mg (nucleotide reverse-transcriptase inhibitors [NRTIs]); (2) once-daily oral dolutegravir 50 mg plus once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg [NRTIs]; or (3) once-daily oral fixed-dose combination of efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg (non-nucleoside reverse transcriptase inhibitors [NNRTIs] or NRTIs). The primary end point was the proportion of viral suppression (HIV-1 RNA concentration: <200 copies per mL) at or within 14 days of delivery. The primary safety outcomes included the occurrence of adverse pregnancy outcomes (preterm delivery, infant small for gestational age, stillbirth, or spontaneous abortion).A total of 617 pregnant women participated: 217 in group 1, 215 in group 2, and 211 in group 3. The median gestational age at enrollment was 21.9 weeks, and the median HIV-1 RNA copies were 902.5 copies/mL. At delivery, 98% of the participants in groups 1 and 2 (395 of 405) had viral suppression, in comparison with 91% (182 of 200) of the participants in group 3 (P = .052; in intention-to-treat analysis). In terms of adverse pregnancy outcomes, there were significantly fewer participants with an adverse pregnancy outcome in group 1 (52 of 216 [24%]) than there were in group 2 (70 of 213 [33%]) or group 3 (69 of 211 [33%]). Children born to mothers in group 3 had higher rates of preterm delivery and neonatal mortality. Of note, however, there was no significant difference in grade ≥3 adverse event outcomes in either mother or child between the 3 groups.The use of dolutegravir in adults including pregnant women as recommended by the World Health Organization is affirmed by this study. Additionally, the use of dolutegravir plus emtricitabine and tenofovir alafenamide fumarate may be favored to the regimen of dolutegravir plus emtricitabine and tenofovir disoproxil fumarate because of the lower incidence of adverse pregnancy outcomes that was seen in this group.Infection with HIV remains a global phenomenon and improving both maternal outcomes during pregnancy and reducing transmission of HIV from mother to child are essential. With this study conducted in many different countries, the authors provide evidence that ART started in pregnancy with dolutegravir induces viral suppression and is associated with better fetal outcomes.

Perceived satisfaction with HIV care and its association with adherence to antiretroviral therapy and viral suppression in the African Cohort Study

BackgroundIncreased availability of HIV care over the past decade has dramatically reduced morbidity and mortality among people living with HIV (PLWH) in sub-Saharan Africa. However, perceived and experienced barriers to care, including dissatisfaction with services, may impact adherence and viral suppression. We examined the associations between satisfaction with HIV care and antiretroviral therapy (ART) adherence and viral load suppression.MethodsThe African Cohort Study (AFRICOS) is a prospective observational study conducted at PEPFAR-supported clinics in four African countries. At enrollment and twice-yearly study visits, participants received a clinical assessment and a socio-behavioral questionnaire was administered. Participants were classified as dissatisfied with care if they reported dissatisfaction with any of the following: waiting time, health care worker skills, health care worker attitudes, quality of clinic building, or overall quality of care received. Robust Poisson regression was used to estimate prevalence ratios and 95% confidence intervals (CIs) for associations between satisfaction with care and ART adherence and between satisfaction with care and viral suppression (viral load < 1000 copies/mL).ResultsAs of 1 March 2020, 2928 PLWH were enrolled and 2311 had a year of follow-up visits. At the first annual follow-up visit, 2309 participants responded to questions regarding satisfaction with quality of care, and 2069 (89.6%) reported satisfaction with care. Dissatisfaction with waiting time was reported by 177 (7.6%), building quality by 59 (2.6%), overall quality of care by 18 (0.8%), health care worker attitudes by 16 (0.7%), and health care worker skills by 15 (0.7%). After adjusting for age and site, there was no significant difference in viral suppression between those who were satisfied with care and those who were dissatisfied (aPR: 1.03, 95% CI 0.97–1.09). Satisfaction with HIV care was moderately associated with ART adherence among AFRICOS participants (aPR: 1.09; 95% CI 1.00–1.16).ConclusionsWhile patient satisfaction in AFRICOS was high and the association between perceived quality of care and adherence to ART was marginal, we did identify potential target areas for HIV care improvement, including reducing clinic waiting times.

Timely initiation of HIV antiretroviral therapy in Haiti 2004-2018: a retrospective cohort study.

ABSTRACTObjective.To describe trends in timing of ART initiation for newly diagnosed people living with HIV before and after Haiti adopted its Test and Start policy for universal HIV antiretroviral therapy (ART) in July 2016, and to explore predictors of timely ART initiation for both newly and previously diagnosed people living with HIV following Test and Start adoption.Methods.This retrospective cohort study explored timing of ART initiation among 147 900 patients diagnosed with HIV at 94 ART clinics in 2004–2018 using secondary electronic medical record data. The study used survival analysis methods to assess time trends and risk factors for ART initiation.Results.Timely uptake of ART expanded with Test and Start, such that same-day ART initiation rates increased from 3.7% to 45.0%. However, only 11.0% of previously diagnosed patients initiated ART after Test and Start. In adjusted analyses among newly diagnosed people living with HIV, factors negatively associated with timely ART initiation included being a pediatric patient aged 0–14 years (HR = 0.23, p < 0.001), being male (HR = 0.92, p = 0.03), being 50+ years (HR = 0.87, p = 0.03), being underweight (HR = 0.79, p < 0.001), and having WHO stage 3 (HR = 0.73, p < 0.001) or stage 4 disease (HR = 0.49, p < 0.001). Variation in timely ART initiation by geographic department and health facility was observed.Conclusions.Haiti has made substantial progress in scaling up Test and Start, but further work is needed to enroll previously diagnosed patients and to ensure rapid ART in key patient subgroups. Further research is needed on facility and geographic factors and on strategies for improving timely ART initiation among vulnerable subgroups.

Survey of pretreatment HIV drug resistance and the genetic transmission networks among HIV-positive individuals in southwestern China, 2014\u20132020

BackgroundPretreatment drug resistance (PDR) can limit the effectiveness of HIV antiretroviral therapy (ART). The aim of this study was to assess the prevalence of PDR among HIV-positive individuals that initiated antiretroviral therapy in 2014–2020 in southwestern China.MethodsConsecutive cross-sectional surveys were conducted in Qinzhou, Guangxi. We obtained blood samples from individuals who were newly diagnosed with HIV in 2014–2020. PDR and genetic networks analyses were performed by HIV-1 pol sequences using the Stanford HIV-database algorithm and HIV-TRACE, respectively. Univariate and multivariate logistic regression models were used to explore the potential factors associated with PDR.ResultsIn total, 3236 eligible HIV-positive individuals were included. The overall prevalence of PDR was 6.0% (194/3236). The PDR frequency to NNRTI (3.3%) was much higher than that of NRTI (1.7%, p < 0.001) and PI (1.2%, p < 0.001). A multivariate logistic regression analysis revealed that PDR was significantly higher among individuals aged 18–29 (adjusted odds ratio (aOR): 1.79, 95% CI 1.28–2.50) or 30–49 (aOR: 2.82, 95% CI 1.73–4.82), and harboring CRF08_BC (aOR: 3.23, 95% CI 1.58–6.59). A total of 1429 (43.8%) sequences were linked forming transmission clusters ranging in size from 2 to 119 individuals. Twenty-two individuals in 10 clusters had the same drug resistant mutations (DRMs), mostly to NNRTIs (50%, 5/10).ConclusionsThe overall prevalence of PDR was medium, numerous cases of the same DRMs among genetically linked individuals in networks further illustrated the importance of surveillance studies for mitigating PDR.

Prevalence of neural tube defects, maternal HIV status, and antiretroviral therapy from a hospital-based birth defect surveillance in Kampala, Uganda.

Background:The estimated prevalence of neural tube defects (NTDs) in Africa is 11.7 per 10,000 live births; however, data on the impact of antiretroviral therapy (ART) during pregnancy and the risk for birth defects in Africa are limited.Methods:Data from a hospital-based surveillance program at four hospitals in Kampala, Uganda were used to estimate the baseline prevalence of NTDs and assess potential associations with HIV status and ART use. All live births, stillbirths, and spontaneous abortions delivered at the participating hospitals affected with selected birth defects between August 2015 and December 2018 were included. Trained midwives collected data from hospital records, maternal interviews, photographs, and narrative descriptions of birth defects. We estimated NTD prevalence per 10,000 births (live, stillbirths, spontaneous abortions), prevalence ratios, and 95% confidence intervals (CIs).Results:A total of 110,752 births from 107,133 women were included in the analysis; 9,394 (8.8%) women were HIV-infected and among those with HIV infection, 95.6% (n = 8,977) were on ART at delivery. Overall, 109 births were affected with NTDs, giving a prevalence of 9.8 (95% CI [8.2, 11.9]). Spina bifida (n = 63) was the most common type of NTD, with a prevalence of 5.7 (95% CI [4.4, 7.3]), followed by anencephaly (n = 31), with a prevalence of 2.8 (95% CI [2.0, 4.0]).Conclusion:The prevalence of NTDs among births in Kampala, Uganda is consistent with current estimates for Africa. With the continued introduction of new medications that may be taken during pregnancy, sustainable birth defect surveillance systems and pharmacovigilance are indicated.

Longitudinal analysis of sociodemographic, clinical and therapeutic factors of HIV-infected individuals in Kinshasa at antiretroviral therapy initiation during 2006-2017.

BackgroundThe benefits of antiretroviral therapy (ART) underpin the recommendations for the early detection of HIV infection and ART initiation. Late initiation (LI) of antiretroviral therapy compromises the benefits of ART both individually and in the community. Indeed, it promotes the transmission of infection and higher HIV-related morbidity and mortality with complicated and costly clinical management.This study aims to analyze the evolutionary trends in the median CD4 count, the median time to initiation of ART, the proportion of patients with advanced HIV disease at the initiation of ART between 2006 and 2017 and their factors.Methods and findingsHIV-positive adults (≥ 16 years old) who initiated ART between January 1, 2006 and December 31, 2017 in 25 HIV care facilities in Kinshasa, the capital of DRC, were eligible. The data were processed anonymously. LI is defined as CD4≤350 cells/μl and/or WHO clinical stage III or IV and advanced HIV disease (AHD), as CD4≤200 cells/μl and/or stage WHO clinic IV. Factors associated with advanced HIV disease at ART initiation were analyzed, irrespective of year of enrollment in HIV care, using logistic regression models.A total of 7278 patients (55% admitted after 2013) with an average age of 40.9 years were included. The majority were composed of women (71%), highly educated women (68%) and married or widowed women (61%). The median CD4 was 213 cells/μl, 76.7% of patients had CD4≤350 cells/μl, 46.1% had CD4≤200 cells/μl, and 59% of patients were at WHO clinical stages 3 or 4. Men had a more advanced clinical stage (p <0.046) and immunosuppression (p<0.0007) than women.Overall, 70% of patients started ART late, and 25% had AHD. Between 2006 and 2017, the median CD4 count increased from 190 cells/μl to 331 cells/μl (p<0.0001), and the proportions of patients with LI and AHD decreased from 76% to 47% (p< 0.0001) and from 18.7% to 8.9% (p<0.0001), respectively.The median time to initiation of ART after screening for HIV infection decreased from 40 to zero months (p<0.0001), and the proportion of time to initiation of ART in the month increased from 39 to 93.3% (p<0.0001) in the same period.The probability of LI of ART was higher in married couples (OR: 1.7; 95% CI: 1.3–2.3) (p<0.0007) and lower in patients with higher education (OR: 0.74; 95% CI: 0.64–0.86) (p<0.0001).ConclusionDespite increasingly rapid treatment, the proportions of LI and AHD remain high. New approaches to early detection, the first condition for early ART and a key to ending the HIV epidemic, such as home and work HIV testing, HIV self-testing and screening at the point of service, must be implemented.

Experiences, perceptions and potential impact of community-based mentor mothers supporting pregnant and postpartum women with HIV in Kenya: a mixed-methods study.

IntroductionCommunity‐based mentor mothers (cMMs) are women living with HIV who provide peer support to pregnant/postpartum women living with HIV (PWLWH) to enhance antiretroviral therapy (ART) adherence, retention in care and prevent perinatal transmission of HIV. The goal of this study was to explore the experiences, perceptions, mechanisms and health impact of cMMs on PWLWH in Kenya from the perspective of cMMs.MethodsWe conducted a prospective mixed‐methods study in southwestern Kenya in 2015–2018. In the qualitative phase, we completed in‐depth interviews with cMMs to explore their perceptions and experiences in supporting PWLWH. Transcripts were broad‐coded according to identified themes, then fine‐coded using an inductive approach. In the quantitative phase, we analysed medical record data from PWLWH who were randomized in the cMM intervention to examine the impact of cMM visits on optimal prevention of mother‐to‐child transmission (PMTCT). We used cluster‐adjusted generalized estimating equation models to examine relationships with a composite outcome (facility delivery, infant HIV testing, ART adherence and undetectable viral load at 6 weeks postpartum). Finally, qualitative and quantitative results were integrated.ResultsConvergence of findings from cMM interviews (n = 24) and PWLWH medical data (n = 589) revealed: (1) The cMM intervention was utilized and perceived as acceptable. PWLWH received, on average, 6.2 of 8 intended home visits through 6 weeks postpartum. (2) The cMMs reported serving as role models and confidantes, supporting PWLWH's acceptance of their HIV status, providing assurances about PMTCT and assisting with male partner disclosure and communication. cMMs also described benefits for themselves, including empowerment and increased income. (3) The cMM visits supported PWLWH's completion of PMTCT steps. Having ≥4 cMM home visits up to 6 weeks postpartum, as compared to <4 visits, was associated with higher likelihood of an optimal PMTCT composite outcome (adjusted relative risk 1.42, p = 0.044).ConclusionsWe found that peer support from cMMs during pregnancy through 6 weeks postpartum was associated with improved uptake of critical PMTCT services and health behaviours and was perceived as beneficial for cMMs themselves. CMM support of PWLWH may be valuable for other low‐resource settings to improve engagement with lifelong ART and HIV services among PWLWH.

Intimate Partner Violence and the HIV Care and Treatment Cascade Among Adolescent Girls and Young Women in DREAMS, South Africa.

Intimate partner violence (IPV) may affect the HIV-treatment cascade. Four high HIV-prevalence DREAMS health districts in South Africa. Secondary analysis of cross-sectional data collected March 2017-June 2018, using random household sample of young (12-24 years) girls and women. Face-to-face interviews assessed IPV and HIV-status knowledge, and finger-prick blood draws assessed ART (antiretroviral therapy) uptake and viral suppression. We used logistic regression to estimate crude and adjusted effects of IPV on HIV knowledge, ART uptake, and viral suppression. Of 18,230 adolescent girls and young women, 8413 (46%) reported ever having had sex, of whom 1118 (13%) were HIV positive. The 90:90:90 benchmarks were 61% knew their status, 86% had ART present in their blood sample, and 91% were virally suppressed. Among the entire sample of young women living with HIV, 65.6% were virally suppressed. Past year IPV was reported by 15%. In adjusted models, IPV trended toward increasing the odds that a young woman was aware she was living with HIV [adjusted odds ratios (aOR) = 1.40, 2.00-9.98, P = 0.067]. There was no association between IPV and reduced treatment use (aOR = 0.73, 0.41-1.29). IPV was independently associated with reduced viral suppression (aOR = 0.30, 0.13-0.66). Addressing the role of IPV in undermining the treatment cascade for adolescent and young women is a critical issue for HIV programming.

Feasibility of Indirect Secondary Distribution of HIV Self-test Kits via WeChat Among Men Who Have Sex With Men: National Cross-sectional Study in China.

BackgroundHIV self-testing (HIVST) kits are common in key sexually active populations. Direct secondary distribution of HIVST kits (DSDHK) is effective in improving the uptake of HIVST. However, there are concerns about the various limitations of DSDHK, including limited geographic reach, payment problems, and need for face-to-face interactions.ObjectiveIn this study, we aim to evaluate the feasibility and characteristics of indirect secondary distribution of HIVST kits (ISDHK) via WeChat (distributing HIVST application links and follow-up HIVST kits to partners) among men who have sex with men (MSM).MethodsFrom October 2017 to September 2019, an HIVST recruitment advertisement was disseminated on the WeChat social media platform to invite MSM to apply for the HIVST kits (referred to as index participants [IPs]). All MSM participants were encouraged to distribute the HIVST application link to their friends and sexual partners (referred to as alters) through their social networks. All the alters were further encouraged to continue distributing the HIVST application link. All participants paid a deposit (US $7), which was refundable upon completion of the questionnaire, and uploaded the test results via a web-based survey system.ResultsA total of 2263 MSM met the criteria and successfully applied for HIVST. Of these, 1816 participants returned their HIVST results, including 1422 (88.3%) IPs and 394 (21.7%) alters. More alters had condomless anal intercourse, a higher proportion of them had never previously tested for HIV, and they showed a greater willingness to distribute HIVST kits to their sexual partners (P=.002) than the IPs. After controlling for age, education, and income, the alters had a greater proportion of MSM who had never tested for HIV before (adjusted odds ratio [aOR] 1.29, 95% CI 1.00-1.68), were more willing to distribute the HIVST application link (aOR 1.71, 95% CI 1.21-2.40), had a lower number of sexual partners (aOR 0.71, 95% CI 0.57-0.90), and were less likely to search for sexual partners on the web (aOR 0.78, 95% CI 0.60-1.02) than IPs. In comparison, the rates of reactive HIVST results, conducting HIV confirmatory tests, HIV seropositivity, and initiation of HIV antiretroviral therapy were similar for IPs and alters.ConclusionsThe ISDHK model of distributing HIVST application links among the MSM population via social media is feasible. The ISDHK model should be used to supplement the DSDHK model to enable a greater proportion of the MSM population to know their HIV infection status.

Antiretroviral therapy for HIV and intrahepatic hepatitis C virus replication.

HIV alters host responses to hepatitis C virus (HCV). However, the impact of antiretroviral therapy (ART) on HCV is rarely understood in relevant tissues and never before within individual hepatocytes. HIV and HCV kinetics were studied before and after ART initiation among 19 HIV/HCV co-infected persons. From five persons with the largest decline in plasma HCV RNA, liver tissues collected before and during ART, when plasma HIV RNA was undetectable, were studied. We used single-cell laser capture microdissection and quantitative PCR to assess intrahepatic HCV. Immunohistochemistry was performed to characterize intrahepatic immune cell populations. Plasma HCV RNA declined by 0.81 (0.52-1.60) log10 IU/ml from a median (range) 7.26 (6.05-7.29) log10 IU/ml and correlated with proportions of HCV-infected hepatocytes (r = 0.89, P = 2 × 10-5), which declined from median (range) of 37% (6-49%) to 23% (0.5-52%) after plasma HIV clearance. Median (range) HCV RNA abundance within cells was unchanged in four of five participants. Liver T-cell abundance unexpectedly decreased, whereas natural killer (NK) and NK T-cell infiltration increased, correlating with changes in proportions of HCV-infected hepatocytes (r = -0.82 and r = -0.73, respectively). Hepatocyte expression of HLA-E, an NK cell restriction marker, correlated with proportions of HCV-infected hepatocytes (r = 0.79). These are the first data to show that ART control of HIV reduces the intrahepatic burden of HCV. Furthermore, our data suggest that HIV affects the pathogenesis of HCV infection by an NK/NK T-cell-mediated mechanism that may involve HLA-E and can be rescued, at least in part, by ART.

HIV care outcomes among transgender persons with HIV infection in the United States, 2006-2021.

HIV prevalence is an estimated 14% among transgender women (TW) and 3% among transgender men (TM). HIV care is vital for viral suppression but is hindered by transphobia and HIV stigma. We assessed HIV care outcomes among transgender persons (TG) with HIV in the United States. Systematic review and meta-analysis of peer-reviewed journal articles. We searched multiple electronic databases and Centers for Disease Control and Prevention's HIV Prevention Research Synthesis database for 2006-September 2020. Eligible reports were US-based studies that included TG and reported HIV care outcomes. Random-effects models were used to calculate HIV care outcome rates. The protocol is registered with PROSPERO (CRD42018079564). Few studies reported outcomes for TM; therefore, only TW meta-analysis results are reported. Fifty studies were identified having low-to-medium risk-of-bias scores. Among TW with HIV, 82% had ever received HIV care; 72% were receiving care, and 83% of those were retained in HIV care. Sixty-two percent were currently virally suppressed. Among those receiving HIV care or antiretroviral therapy (ART), 67% were virally suppressed at last test. Sixty-five percent were linked to HIV care 3 months or less after diagnosis. Seventy-one percent had ever been prescribed ART. Approximately 66% were taking ART, and 66% were ART-adherent. Only 56% were currently adherent the previous year. HIV care outcomes for TW were not ideal, and research gaps exists for TM. High heterogeneity was observed; therefore, caution should be taken interpreting the findings. Integrating transgender-specific health needs are needed to improve outcomes of transgender persons across the HIV care continuum.

Decreased Activated CD4+ T Cell Repertoire Diversity After Antiretroviral Therapy in HIV-1/HCV Coinfection Correlates with CD4+ T Cell Recovery.

Dysfunctional immune activation accumulates during chronic viral infection and contributes to disease pathogenesis. In HIV-1, immune activation is exacerbated by concurrent infection with hepatitis C virus (HCV), accelerating depletion of CD4+ T cells. HIV-1 suppression with antiretroviral therapy (ART) generally reconstitutes CD4+ T cell counts, while also reducing the proportion that is activated. Whether this immune reconstitution also reduces the complexity of the CD4+ T cell population is unknown. We sought to characterize the relationship between activated CD4+ T cell repertoire diversity and immune reconstitution following ART in HIV-1/HCV coinfection. We extracted T cell receptor (TCR) sequences from RNA sequencing data obtained from activated CD4+ T cells of HIV-1/HCV coinfected individuals before and after treatment with ART (clinical trial NCT01285050). There was notable heterogeneity in both the extent of CD4+ T cell reconstitution and in the change in activated CD4+ TCR repertoire diversity following ART. Decreases in activated CD4+ TCR repertoire diversity following ART were predictive of the degree of CD4+ T cell reconstitution. The association of decreased activated CD4+ TCR repertoire diversity and improved CD4+ T cell reconstitution may represent loss of nonspecifically activated TCR clonotypes, and possibly selective expansion of specifically activated CD4+ clones. These results provide insight into the dynamic relationship between activated CD4+ TCR diversity and CD4+ T cell recovery of HIV-1/HCV coinfected individuals after suppression of HIV-1 viremia.

Trends in hospitalizations and deaths in HIV-infected patients in Spain over two decades.

The prognosis of HIV infection dramatically improved after the introduction of triple antiretroviral therapy 25 years ago. Herein, we report the impact of further improvements in HIV management since then, looking at all hospitalizations in persons with HIV (PWH) in Spain. A retrospective study using the Spanish National Registry of Hospital Discharges. Information was retrieved since 1997-2018. From 79 647 783 nationwide hospital admissions recorded during the study period, 532 668 (0.67%) included HIV as diagnosis. The mean age of PWH hospitalized increased from 33 to 51 years (P < 0.001). The rate of HIV hospitalizations significantly declined after 2008. Comparing hospitalizations during the first (1997-2007) and last (2008-2018) decades, the rate of non-AIDS illnesses increased, mostly due to liver disease (from 35.9 to 38.3%), cardiovascular diseases (from 12.4 to 28.2%), non-AIDS cancers (from 6.4 to 15.5%), and kidney insufficiency (from 5.4 to 13%). In-hospital deaths occurred in 5.5% of PWH, declining significantly over time. Although most deaths were the result from AIDS conditions (34.8%), the most frequent non-AIDS deaths were liver disease (47.1%), cardiovascular events (29.2%), non-AIDS cancers (24.2%), and kidney insufficiency (20.7%). Hospital admissions in PWH significantly declined after 2008, following improvements in HIV management and antiretroviral therapy. Non-AIDS cancers, cardiovascular events and liver disease represent a growing proportion of hospital admissions and deaths in PWH.

"He is the Same as Me": Key Populations' Acceptability and Experience of a Community-Based Peer Navigator Intervention to Support Engagement in HIV Care in Tijuana, Mexico.

Engagement in the HIV care continuum among people living with HIV is essential to prevent ongoing transmission. Although there is evidence for the need for comprehensive approaches (e.g., peer navigation) to improve the HIV care continuum, there is limited knowledge of how the peer navigation model might work to improve the HIV care continuum in low resource settings among Latinx key populations (e.g., persons who inject drugs, female sex workers, men who have sex with men, and transgender women). Therefore, this article aims to qualitatively assess members of key populations' acceptability of Conexiones Saludables (Healthy Connections), a community-based peer navigation intervention implemented in Tijuana, Mexico. This analysis draws upon the postintervention survey data from 34 participants and data from qualitative interviews with 10 participants. Participants found the intervention to be acceptable and discussed the ways in which peer navigators were influential in educating participants about HIV, antiretroviral therapy (ART), linking participants to existing HIV care and ancillary services in Tijuana, and in providing emotional and instrumental support to facilitate engagement in HIV treatment and ART adherence. The intervention emphasized the use of peer navigators who had a deep understanding of the sociostructural barriers (e.g., substance use, homelessness) that HIV-positive key populations face in Tijuana. Findings from this study may inform programs with highly vulnerable populations in similar settings.

Linear and non-linear analysis of heart rate variability in HIV-positive patients on two different antiretroviral therapy regimens

BackgroundCardiac autonomic dysfunction in HIV+ patients on different antiretroviral therapy (ART) regimens has been described. We aimed to characterize parameters of heart rate variability (HRV) and correlate with different classes of ART in HIV+ patients in three experimental conditions: rest, cold face, and tilt tests.MethodsCross-sectional study with three groups of age- and gender-matched individuals: group 1, 44 HIV+ patients undergoing combination therapy, with two nucleoside reverse transcriptase inhibitors (NRTI) and one non-nucleoside reverse transcriptase inhibitor (NNRTI); group 2, 42 HIV+ patients using two NRTI and protease inhibitors (PI’s); and group 3, 35 healthy volunteers with negative HIV serology (control group). Autonomic function at rest and during cold face- and tilt-tests was assessed through computerized analysis of HRV, via quantification of time- and frequency domains by linear and non-linear parameters in the three groups.ResultsAnthropometric and clinical parameters were similar between both HIV groups, except CD4+ T lymphocytes, which were significantly lower in group 2 (p = 0.039). At baseline, time-domain linear HRV parameters, RMSSD and pNN50, and the correlation dimension, a non-linear HRV parameter (p < 0.001; p = 0.018; p = 0.019, respectively), as well as response of RMSSD to cold face test were also lower in the HIV+ group than in the control individuals (p < 0.001), while no differences among groups were detected in HRV parameters during the tilt test.ConclusionsDespite ART regimens, HIV+ patients presented lower cardiac vagal modulation than controls, whereas no difference was observed among the HIV groups, suggesting that higher cardiovascular risk linked to PIs may be associated with factors other than autonomic dysfunction.

Time trends in cancer incidence in Australian people living with HIV between 1982 and 2012.

The aim of the study was to describe time trends in cancer incidence in people living with HIV (PLHIV) in Australia between 1982 and 2012. A population-based prospective study was conducted using data linkage between the national HIV and cancer registries. Invasive cancers identified in PLHIV were grouped into AIDS-defining cancers (ADCs), infection-related non-ADCs (NADCs), and non-infection-related NADCs. Crude and age-standardized incidence rates of cancers were calculated and compared over five time periods: 1982-1995, 1996-1999, 2000-2004, 2005-2008 and 2009-2012, roughly reflecting advances in HIV antiretroviral therapy. Standardized incidence ratios (SIRs) compared with the Australian general population were calculated for each time period. Generalized linear models were developed to assess time trends in crude and age-standardized incidences. For ADCs, the crude and age-standardized incidences of Kaposi sarcoma and non-Hodgkin lymphoma substantially declined over time (P-trend <0.001 for all) but SIRs remained significantly elevated. For infection-related NADCs, there were significant increases in the crude incidences of anal, liver and head and neck cancers. Age-standardized incidences increased for anal cancer (P-trend = 0.002) and liver cancer (P-trend <0.001). SIRs were significantly elevated for anal cancer, liver cancer and Hodgkin lymphoma. For non-infection-related NADCs, the crude incidence of colorectal, lung and prostate cancers increased over time, but age-standardized incidences remained stable. Continuous improvements and high coverage of antiretroviral therapy have reduced the incidence of ADCs in PLHIV in Australia. Clinical monitoring of anal and liver cancers in people living with HIV should be performed, given the increasing incidence of these cancers.

An assessment of factors associated with neurocognitive decline in people living with HIV.

Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) remains a health concern. However, limited research has been done to identify factors associated with neurocognitive decline. We assessed risk factors associated with neurocognitive decline in people living with HIV using a definition of decline that is statistically easy to adopt, is based on a commonly used neuropsychological cut-off and may be clinically relevant. Cox proportional hazards modeling was performed using the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study database. 581 participants were followed for up to 12years. Neurocognitive decline was defined as the first observed drop in global T-scores of at least 2.67. Lifetime methamphetamine use had the strongest association with neurocognitive decline (adjusted Hazard Ratio; aHR = 1.48; 95% CI = 0.92-2.39) followed by no current antiretroviral medication use (aHR = 1.32; 95% CI = 0.91-1.92). Other risk factors included Hispanic ethnicity, lifetime history of major depressive disorder, lifetime cannabis use, hepatitis-C infection, and difficulty eating, dressing, bathing, or using the toilet. Results indicate that consistent use of ART may be of high significance to preserving neurocognition. Furthermore, Hispanic patients, those with a history of depression and substance use, and those having difficulty in essential activities of daily living may require vigilant follow-up.

Cardiovascular toxicity of contemporary antiretroviral therapy.

HIV treatment has evolved since the introduction of antiretroviral therapy (ART) in the 1990s. Earlier treatment strategies, and the introduction of integrase inhibitors in preferred first-line ART have fundamentally changed cardiovascular side effects due to HIV infection and ART. This review provides an update on cardiovascular toxicity of contemporary ART. Cardiovascular disease (CVD) risk, including heart failure, is still increased in people living with HIV (PLWH). Exposure to older antiretrovirals, including stavudine and zidovudine, still impact on CVD risk through persistent changes in body fat distribution years after discontinuation. Protease inhibitors (PI) and efavirenz have associated metabolic disturbances and increased risk of CVD, although use is decreasing worldwide. Integrase inhibitors and CCR5 antagonists seem to have negligible immediate CVD toxicity. Weight gain on newer antiretrovirals including integrase inhibitors is a reason for concern. CVD risk should be monitored carefully in PLWH who were exposed to first generation ART, efavirenz or to PIs. Registries should capture ART use and CVD events to stay informed on actual clinical risk in the current era of rapid initiation on integrase inhibitor-based ART.

HIV And HCV adherence and treatment outcomes among people who inject drugs receiving opioid agonist therapy

ABSTRACT Among people who inject drugs (PWID), 60% have HCV and 50–90% of HIV-infected PWID are co-infected with HCV. Data comparing adherence to direct-acting antiviral (DAA) therapy among HCV mono-infected and HIV/HCV co-infected PWID is limited. The impact of HCV treatment initiation on HIV antiretroviral therapy (ART) adherence is also poorly understood. We assessed DAA adherence in HCV mono-infected and HIV/HCV co-infected PWID and examined changes in ART adherence and HIV outcomes following HCV treatment. Study was conducted in three Medication for Opioid use Disorder (MOUD) programs in Bronx, New York. HCV treatment adherence was measured using electronic blister packs. 2-week DAA adherence rates were compared and controlled for study arm, psychiatric illness and alcohol intoxication within the past 30 days. ART adherence was measured using participant self-report and dichotomized to “excellent” or “other”. ART adherence, CD4 count, and HIV viral load were identified six months prior to, during, and six months after HCV treatment. Statistical significance was assessed with mixed-effects regression linear or logistic models. Overall DAA adherence rates among HCV mono-infected and HIV/HCV co-infected PWID were 74% (95% CI=71–78%) and 76% (95%CI=70–83%), respectively (p=.55). There were no significant changes in ART adherence, CD4 counts, or HIV viral loads prior to, during, or after HCV treatment. This is the first study assessing the impact of DAA therapy on ART adherence and HIV treatment outcomes among PWID. It is one of the first to compare DAA adherence among HCV and HIV/HCV co-infected PWID. Our data demonstrate no significant difference in DAA adherence and no significant impact of HCV treatment on ART adherence or HIV outcomes.

Associations between HIV, antiretroviral therapy and preterm birth in the US Women's Interagency HIV Study, 1995-2018: a prospective cohort.

To evaluate the associations of HIV infection with preterm birth (PTB), and of HIV antiretroviral therapy (ART) with PTB. We analysed singleton live-born pregnancies among women from 1995 to 2019 in the Women's Interagency HIV Study, a prospective cohort of US women with, or at risk for, HIV. The primary exposures were HIV status and ART use before delivery [none, monotherapy or dual therapy, or highly active antiretroviral therapy (HAART)]. The primary outcome was PTB <34weeks, and, secondarily, <28 and <37weeks. We analysed self-reported birth data, and separately modelled the associations between HIV and PTB, and between ART and PTB, among women with HIV. We used modified Poisson regression, and adjusted for age, race, parity, tobacco use and delivery year, and, when modelling the impact of ART, duration from HIV diagnosis to delivery, nadir CD4 count, and pre-pregnancy viral load and CD4 count. We analysed 488singleton deliveries (56% exposed to HIV) to 383 women. The risk of PTB <34weeks was similar among women with and without HIV, but the risk of PTB <37weeks was higher [32% vs. 23%; adjusted risk ratio (aRR) = 1.43; 95% confidence interval (CI): 1.07-1.91] among women with HIV. The risk of PTB <34weeks was lower among women with HIV receiving HAART than among those receiving no ART (7% vs. 26%; aRR:0.19; 95% CI: 0.08-0.44). The associations between HAART and PTB <28 and <37weeks were similar. Antiretroviral therapy exposure was associated with a decreased risk of PTB among a US cohort of women with HIV. Given the growing concerns about ART and adverse pregnancy outcomes, this finding that ART may be protective for PTB is reassuring.