Association Of Antiretroviral Therapy Research Articles

Association of Integrase Strand Transfer Inhibitor-Based Antiretroviral Therapy With Blood Pressure and Sustained Hypertension in People With Human Immunodeficiency Virus.

Integrase strand transfer inhibitors (INSTIs) are a commonly used antiretroviral therapy (ART) class in people with human immunodeficiency virus (HIV) and associated with weight gain. We studied the association of INSTI-based ART with systolic and diastolic blood pressure (SBP and DBP). We recruited 50 people taking INSTI-based ART and 40 people taking non-INSTI-based ART with HIV and hypertension from the University of Alabama at Birmingham HIV clinic. Office BP was measured unattended using an automated (AOBP) device. Awake, asleep, and 24-hour BP were measured through ambulatory BP monitoring. Among participants with SBP ≥130 mm Hg or DBP ≥80 mm Hg on AOBP, sustained hypertension was defined as awake SBP ≥130 mm Hg or DBP ≥80 mm Hg. Mean SBP and DBP were higher among participants taking INSTI- vs. non-INSTI-based ART (AOBP-SBP/DBP: 144.7/83.8 vs. 135.3/79.3 mm Hg; awake-SBP/DBP: 143.2/80.9 vs. 133.4/76.3 mm Hg; asleep-SBP/DBP: 133.3/72.9 vs. 120.3/65.4 mm Hg; 24-hour-SBP/DBP: 140.4/78.7 vs. 130.0/73.7 mm Hg). After multivariable adjustment, AOBP, awake, asleep, and 24-hour SBP were 12.5 (95% confidence interval [CI] 5.0-20.1), 9.8 (95% CI 3.6-16.0), 10.4 (95% CI 2.0-18.9), and 9.8 (95% CI 4.2-15.4) mm Hg higher among those taking INSTI- vs. non-INSTI-based ART, respectively. AOBP, awake, asleep, and 24-hour DBP were 7.5 (95% CI 0.3-14.6), 6.1 (95% CI 0.3-11.8), 7.5 (95% CI 1.4-13.6), and 6.1 (95% CI 0.9-11.3) mm Hg higher among those taking INSTI- vs. non-INSTI-based ART after multivariable adjustment. All participants had SBP ≥130 mm Hg or DBP ≥80 mm Hg on AOBP and 97.9% and 65.7% of participants taking INSTI- and non-INSTI-based ART had sustained hypertension, respectively. INSTI-based ART was associated with higher SBP and DBP than non-INSTI-based ART.

No Evidence for an Association of HIV and Antiviral Treatment With Changes in Framingham Cardiovascular Risk Score in the Ndlovu Cohort Study.

HIV and antiretroviral therapy (ART) have been associated with increased cardiovascular disease (CVD) risk in high-income countries. The authors studied the longitudinal association between HIV and ART and nonlaboratory Framingham Risk Score (FRS) in a middle-income country. This longitudinal analysis of the NCS (Ndlovu Cohort Study), South Africa used baseline to 36-month follow-up data. Demographics, HIV, ART status, and cardiometabolic measures were obtained. FRS was used as a CVD risk measure. Through linear mixed models, FRS trends over time and the association with HIV were studied. Analysis included 1136 participants, with 609 (54%) having HIV, and 495 (81%) taking ART. At baseline, 9.8% of participants had a high FRS. People living with HIV (PLHIV) had a 3.2% lower FRS than HIV-negative participants (P<0.001). FRS increased similarly for both groups over time. Other factors associated with FRS were secondary and higher education (ß value: -0.075, P<0.001; ß value: -0.084, P<0.001) and alcohol consumption (ß value: 0.011, P<0.001). CVD risk increased for all participants over 36 months, suggesting classic risk factors rather than HIV status or ART to be drivers of CVD risk. People living with HIV had a significantly lower FRS than their HIV-negative counterparts, possibly related to HIV itself or a more frequent interaction with healthcare services. No association of HIV and ART with changes in FRS over 36 months was observed, suggesting the need for research using clinical endpoints to elucidate the effects of HIV and ART on CVD risk. Population-based prevention of CVD risk factors in sub-Saharan Africa is warranted, regardless of HIV status.

Association of Antiretroviral Therapy with Platelet Function and Systemic Inflammatory Response in People Living with HIV: A Cross-Sectional Study.

People living with HIV (PLWHIV) present an increased risk of adverse cardiovascular events. We aimed to assess whether antiretroviral therapy (ART) pharmacologically enhances platelet reactivity and platelet activation intensity, and explore the potential association with underlying inflammatory status. This was a cross-sectional cohort study carried out among PLWHIV on diverse ART regimens. Platelet reactivity and activation intensity were assessed using the bedside point-of-care VerifyNow assay, in P2Y12 reaction units (PRU), measurements of monocyte-platelet complexes, and P-selectin and GPIIb/IIIa expression increase, following activation with ADP, respectively. Levels of major inflammatory markers and whole blood parameters were also evaluated. In total, 71 PLWHIV, 59 on ART and 22 healthy controls, were included in this study. PRU values were significantly elevated in PLWHIV compared to controls [Mean; 257.85 vs. 196.67, p < 0.0001], but no significant differences were noted between ART-naïve or ART-experienced PLWHIV, or between TAF/TDF and ABC based regimens, similar to systemic inflammatory response. However, within-group analysis showed that PRUs were significantly higher in ABC/PI vs ABC/INSTI or TAF/TDF + PI patients, in line with levels of IL-2. PRU values did not correlate strongly with CD4 counts, viral load, or cytokine values. P-selectin and GPIIb/IIIa expression increased following ADP activation and were significantly more prominent in PLWHIV (p < 0.005). Platelet reactivity and platelet activation intensity were shown to be increased in PLWHIV, but they did not appear to be related to ART initiation, similar to the underlying systemic inflammatory response.

Toward Ending the HIV Epidemic: Temporal Trends and Disparities in Early ART Initiation and Early Viral Suppression Among People Newly Entering HIV Care in the United States, 2012-2018.

In 2012, the US Department of Health and Human Services updated their HIV treatment guidelines to recommend antiretroviral therapy (ART) for all people with HIV (PWH) regardless of CD4 count. We investigated recent trends and disparities in early receipt of ART prescription and subsequent viral suppression (VS). We examined data from ART-naïve PWH newly presenting to HIV care at 13 North American AIDS Cohort Collaboration on Research and Design clinical cohorts in the United States during 2012-2018. We calculated the cumulative incidence of early ART (within 30 days of entry into care) and early VS (within 6 months of ART initiation) using the Kaplan-Meier survival function. Discrete time-to-event models were fit to estimate unadjusted and adjusted associations of early ART and VS with sociodemographic and clinical factors. Among 11 853 eligible ART-naïve PWH, the cumulative incidence of early ART increased from 42% in 2012 to 82% in 2018. The cumulative incidence of early VS among the 8613 PWH who initiated ART increased from 83% in 2012 to 93% in 2018. In multivariable models, factors independently associated with delayed ART and VS included non-Hispanic/Latino Black race, residence in the South census region, being a male with injection drug use acquisition risk, and history of substance use disorder (SUD; all P ≤ .05). Early ART initiation and VS have substantially improved in the United States since the release of universal treatment guidelines. Disparities by factors related to social determinants of health and SUD demand focused attention on and services for some subpopulations.

Integrase Strand Transfer Inhibitors &amp; Weight Gain in Children with Perinatal HIV

Background: In the past, HIV infection was associated with weight loss due to metabolic wasting. Now with early initiation of antiretroviral therapy (ART) an increasing number of patients are being classified as overweight/ obese both prior to initiation and during the course of ART. Certain integrase strand transfer inhibitors (INSTIs) have been associated with weight gain in the adult population, but data in the pediatric population is lacking. This study explores the association of ART with an INSTI backbone and changes in weight and body mass index (BMI) in children with perinatal HIV who are followed in the HIV clinic at Riley Hospital.&#x0D; Methods: We performed a retrospective review of 59 patients with perinatally acquired HIV from 2016 to 2021. Weight, BMI, z-score, blood pressure (BP) percentiles, and lipid panels were recorded from the patients’ most recent visit. BMI and BP percentiles were compared between patients on Bictegravir, Dolutegravir, and Elvitegravir. For patients currently on an INSTI-backbone ART regimen, BMI was compared before and up to 5 years after INSTI initiation.&#x0D; Results: In our cross-sectional analysis between patients on Bictegravir, Dolutegravir, and Elvitegravir there was no significant difference in BMI (p=0.859), systolic BP percentile (p=0.188), or diastolic BP percentile (p=0.541). In our longitudinal analysis, we observed a significant increase in BMI over 3 years compared to pre-INSTI initiation (p=0.049). In addition, we observed an upwards trend with patients on Bictegravir (p=0.094) and Elvitegravir (p=0.121).&#x0D; Conclusion/Impact: Our study suggests that ART regimens with an INSTI backbone are associated with greater increases in BMIs. Our study is limited by a small n, but provides pilot data to direct future studies. It also illustrates that emphasis on healthy body weight maintenance may be necessary when patients are placed on ART regimens with INSTI backbones.

A Matter of Fat: Body Fat Distribution and Cardiometabolic Disease in Africa.

Africa is a complex and diverse continent that faces numerous challenges. It is a region in epidemiological transition which is currently experiencing a dual burden of communicable and non-communicable diseases. The high prevalence of cardiometabolic disease (CMD) on the continent is driven largely by the increasing prevalence of obesity in the more affluent African nations. Although epidemiological studies demonstrate that a greater level of total body fat is associated with a higher risk for CMD, there is a complex association between body fat distribution and CMD risk. Thus, visceral adipose tissue (VAT) is considered a prime etiological agent for CMD, while subcutaneous adipose tissue (SAT) may act as a protective factor. The literature demonstrates positive correlations of VAT with type 2 diabetes, hypertension, and atherogenic dyslipidemia. However, the mechanisms via which VAT and SAT modulate CMD risk in African patients require further investigation. In addition, studies from high-income countries have shown that HIV and antiretroviral therapy (ART) are associated with changes in body fat distribution and higher risk for CMDs. The prevalence of HIV infection is at its highest in sub-Saharan Africa. However, cross-sectional studies from this region have produced contradictory results on the association of HIV and ART with CVD risk factors, and data is required from large prospective studies to clarify these relationships.

Antiretroviral Therapy and Detection of High-grade Cervical Intraepithelial Neoplasia (CIN2+) at Post-CIN Management Follow-up Among Women Living With Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis.

We evaluated the association of antiretroviral therapy (ART), CD4+ count and human immunodeficiency virus (HIV) plasma viral load (PVL) on high-grade cervical intraepithelial neoplasia (CIN2+) detection at follow-up after CIN management among women living with HIV (WLHIV). Medline, Embase, Global Health, and PubMed were searched from 1 January 1996 to 15 January 2020. Eligible studies investigated the association of ART, CD4+ count, or HIV PVL on histology-confirmed CIN2+ detection at follow-up. Summary estimates were obtained using random-effects meta-analyses; heterogeneity was examined using I2 statistic. PROSPERO registration: CRD42018115631. Eight studies representing 9 populations were identified, including 1452 WLHIV followed between 6 and 33 months post-CIN management. Pooled data from 8 populations (n = 1408) suggested weak evidence of a decreased risk of CIN2+ detection at follow-up among ART users compared to ART-naive women (crude odds ratio [cOR] = 0.70, 95% confidence interval [CI]: .36-1.36; I2 = 64.5%, P = .006; adjusted risk ratio [aRR] from 3 studies = 0.66, 95% CI: .20-2.24; I2 = 78.7%, P = .009). A significant association was observed in high-income countries (cOR = 0.24, 95% CI: .13-.45; I2 = 0.0%, P = .77) but not in low and middle-income countries (cOR = 1.13, 95% CI: .67-1.92; I2 = 18.8%, P = .30).In 3 populations, ART users with HIV PVL <50 copies/ml were less likely to have CIN2+ detection at follow-up (vs ≥50 copies/mL: cOR = 0.55, 95% CI: .32-.94; I2 = 0.0%, P = .23).There was weak evidence of decreased CIN2+ detection at follow-up among WLHIV with higher contemporary CD4+ cell counts (≥200 cells/µL vs <200 cells/µL [cOR = 0.36, 95% CI: .04-3.13; I2 = 81.3%, P = .021]) and significant evidence among women with a higher nadir CD4+ count (≥350 cells/µl vs <200 cells/µl [adjusted hazard ratio [aHR] = 0.35, 95% CI: .15-.84; I2 = 0%, P = .64]). ART may reduce the risk of CIN2+ detection at follow-up; this effect is most likely enhanced by a combination of adequate HIV control and excisional CIN treatment. Our findings support recommendations of early ART and the integration of CIN2+ screening and management into HIV care.

Association of antiretroviral therapy with anal high-risk human papillomavirus, anal intraepithelial neoplasia, and anal cancer in people living with HIV: a systematic review and meta-analysis

The effect of antiretroviral therapy (ART) on the natural history of anal high-risk HPV and anal lesion progression is not well established. We reviewed the association of ART and other HIV-related factors on anal HPV infection, anal intraepithelial neoplasia (AIN), and anal cancer among people living with HIV. For this systematic review and meta-analysis, we searched MEDLINE and EMBASE for studies published between Jan 1, 1996, and Oct 30, 2019, that reported the association of HIV-related exposures (ART or highly active ART [HAART], HIV-RNA plasma viral load [PVL], and nadir or current CD4 cell count) with outcomes of anal high-risk HPV prevalence, incidence, and persistence; prevalence, incidence, progression, or regression of anal histological and cytological abnormalities; and anal cancer incidence. Effect estimates were extracted whenever available; otherwise, they were calculated from raw data. We assessed the risk of bias of included studies using the Newcastle-Ottawa scale, and random-effects meta-analyses were done to examine heterogeneity using the I2 statistic. This study is registered on the PROSPERO database, CRD42018007271. We identified 6777 studies, of which 5377 were excluded before full-text review. 122 studies providing estimates for 130 distinct populations matched the inclusion criteria. The populations comprised 417 006 people living with HIV (women, men who have sex with men, and men who have sex with women). 41 (32%) population estimates were not stratified by sex or sexual orientation. People living with HIV receiving ART had 35% lower high-risk HPV prevalence than ART-naive people (crude odds ratio [OR] 0·65, 95% CI 0·54-0·79; I2 12·1%, p=0·31) in 18 studies, and prolonged ART use was associated with a 10% reduction per year in high-risk HPV prevalence in two studies (adjusted OR 0·90, 0·85-0·95; I2 0%, p=0·88). People living with HIV with undetectable PVL had lower HSIL-AIN2+ prevalence than those with detectable PVL (crude OR 0·84, 0·72-0·98; I2 0%, p=0·80) in 16 studies, particularly if sustained for more than 1 year (crude OR 0·62, 0·47-0·81; I2 0%, p=0·51). ART was not associated with anal cancer incidence when adjusted for years living with HIV in three studies (adjusted hazard ratio [HR] 1·11, 95% CI 0·68-1·80; I2 0%, p=0·57), but ART users with sustained undetectable HIV PVL had 44% lower risk of anal cancer than those without (adjusted HR 0·56, 0·44-0·70; I2 0%, p=0·94) and for each increase in nadir CD4 cell counts of 100 cells per μL, there was a 40% decrease in anal cancer incidence (crude HR 0·60, 0·46-0·78; I2 21·7%, p=0·26). Effective ART use and early initiation at high nadir CD4 counts might reduce anal high-risk HPV infection and anal cancer risk. Although most studies were cross-sectional in design and few adjusted for potential confounders, this analysis provides comprehensive estimates of the effect of ART and HIV-related factors on the natural history of anal HPV-related disease in people living with HIV. EU Marie Skłodowska-Curie Actions programme.

Cervical neoplastic lesions in relation to CD4 T-lymphocyte counts and antiretroviral therapy among women with clinical stage 1 HIV in Yunnan, China.

China lacks data demonstrating associations of cervical neoplastic lesions with CD4 T-lymphocyte (CD4 cell) counts and antiretroviral therapy (ART) among HIV-infected women, suggesting relevant investigations are needed. A total of 545 HIV-infected women were enrolled in Yunnan, China, between 2011 and 2013. CD4 cell counts and ART were measured via medical records and cervical neoplastic lesions were measured by professional pathologists. Multivariable logistic models, which treated cervical intraepithelial neoplasia (CIN) 1+ and CIN2+ as outcomes, calculated adjusted odds ratio (aOR) of CD4 cell counts and ART. Subgroup analysis treating CIN1+ as the outcome was conducted by HIV infection duration (<4 vs ≥4 years), ethnicity (Han vs non-Han), and study site (Mangshi vs Kunming). The prevalence of CIN1+ and CIN2+ was 17.4% and 7.3%, respectively. Overall, 243 (44.6%) women had CD4 cell counts ≥500 cell/μL, 187 (34.3%) used ART for less than 2 years, and 236 (43.3%) used ART for at least 2 years. We found inverse associations of CIN1+ with CD4 cell counts (≥500 compared to <500 cells/μL: aOR = 0.46, 95% CI = 0.27-0.79) and ART use (<2 years: aOR = 0.43, 95% CI = 0.21-0.87; ≥2 years: aOR = 0.54, 95% CI = 0.27-1.10). Point estimates did not change substantially for CIN2+ but aORs of ART became nonsignificant. No significant interaction was observed for HIV infection duration. We found significant interaction between CD4 cell counts and ethnicity and study site in relation to CIN1+. Our study suggests potential protective effects of high CD4 cell counts against cervical neoplastic lesions among HIV-infected women, whereas associations of ART are less consistent.

No association between early antiretroviral therapy during pregnancy and plasma levels of angiogenic factors: a cohort study

BackgroundEarly antiretroviral therapy (ART) during pregnancy has dramatically reduced the risk of perinatal HIV transmission. However, studies have shown an association between premature delivery and the use of ART during pregnancy (particularly protease inhibitor (PI)-based therapies), which could be explained by placental dysfunction. The objective of this study was to evaluate the association of ART (class, duration of exposure and time of initiation) with placental function by using angiogenic factors placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) as biomarkers.MethodsClinical and biological data from 159 pregnant women living with HIV were analyzed. Levels of each biomarker were measured in the first and second trimester of pregnancy. After logarithmic transformation, we compared these using generalized estimating equations according to (a) the type of ART; (b) the duration of exposure to ART; and (c) the time of initiation of ART.ResultsAfter adjusting for variables such as ethnicity, maternal age, gestational age, body mass index, parity, smoking status, and sex of the fetus, we found no significant association between the class of ART (PI-based or not) and serum concentrations of PlGF or sFlt-1. Furthermore, no significant association was found between biomarker levels and the duration of ART exposure or the timing of ART initiation (pre- or post-conception).ConclusionsThis study suggests that first and second trimester angiogenic factor levels are not significantly associated with ART, regardless of the duration or type (with or without PI). These observations seem reassuring when considering the use of ART during early pregnancy.

Thyroid function in individuals living with human immunodeficiency virus: the concern and debate about regular screening

Abnormal thyroid functions are common among individuals living with human immunodeficiency virus (HIV). Potent antiretroviral therapy can induce abnormalities in thyroid function or it can be related to drug interactions and the immune reconstitution inflammatory syndrome (IRIS). Increasing prevalence of thyroid dysfunction has been reported in individuals living with HIV (LWHIV). However, there is insufficient evidence to recommend routine thyroid screening of asymptomatic individuals. Hence, in this review we report the common thyroid dysfunctions associated with HIV and in association of anti-retroviral therapy (ART); after critical review of PubMed and Google scholar published-English literature since 1996. HIV can be associated with hypothyroidism, hyperthyroidism and also may increase the risk of thyroid cancer. Emerging evidence also showed that in well treated individuals LWHIV, thyroid function may not be affected by HIV. Therefore, it is a good clinical practice to screen for thyroid function once every 12–24 months. Currently there is little research about the impact of aging in thyroid function in individuals living with HIV. Further research is also needed to establish the value and interval of regular screening of thyroid function in individuals living with HIV.

Cocaine use modifies the association between antiretroviral therapy and endothelial dysfunction among adults with HIV infection.

Cocaine is commonly used among HIV-infected people and may worsen HIV disease progression. In addition, existing evidence suggests a link between antiretroviral regimens and endothelial dysfunction. This study aimed to examine whether the associations of antiretroviral therapy (ART) regimens with endothelial dysfunction may be modified by cocaine use in adults with HIV infection. Between 2003 and 2014, 466 HIV-positive participants residing in Baltimore, Maryland, were enrolled in a study investigating comorbidities associated with HIV/ART. The associations between various risk factors and endothelial dysfunction indicators were examined by robust regression models fitted for the overall subjects and cocaine subgroups, separately. Duration of nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy was negatively associated with plasma vWF:Ag levels in cocaine non-users (β = -.715, SE = .220, P < .05). However, cocaine users on longer-term NNRTI-based regimens had greater plasma endothelin-1 (ET-1) concentrations than their counterparts (β = .003, SE = .001, P < .05). In addition, current cigarette smoking was significantly positively associated with ET-1 concentrations in both cocaine non-users (β = .609, SE = .164, P < .05) and cocaine users (β = .331, SE = .086, P < .05). In conclusion, cocaine use modified the potential effects of NNRTI-based therapy on biomarkers of endothelial dysfunction. These findings suggested that reduction in cocaine use may improve endothelial function in HIV-infected cocaine users.

The association between antiretroviral therapy and early placental function: a cohort study

Objective: To evaluate the association of antiretroviral therapy (ART) type and duration of exposure with early placental function using biomarkers of aneuploidy screening.Study design: Three hundred thirty-eight pregnant women living with HIV were enrolled in two Canadian centers. Multiple linear regressions were performed adjusting for confounding factors (race, age, gestational age, body mass index, parity, smoking, and fetal sex).Results: Women receiving ART had significantly increased second trimester alpha-fetoprotein (AFP) levels (β = 0.147, 95% CI = [0.067–0.227] for protease inhibitor-based ART and β = 0.176, 95% CI = [0.080–0.272] for ART without protease inhibitor) compared to women who received no treatment. However, there was no significant association between ART type and the levels of free β-human chorionic gonadotrophin (β-hCG), pregnancy-associated plasma protein-A (first trimester), unconjugated estriol, total hCG, and inhibin A (second trimester). No significant association was shown between biomarker levels and duration of ART exposure.Conclusion: Early placental function does not appear to be significantly affected by ART, except for AFP.

112 Associations of Anti-Retroviral Therapy Following Kidney Transplantation on Incident BK Viremia

112 Associations of Anti-Retroviral Therapy Following Kidney Transplantation on Incident BK Viremia

Association of antiretroviral therapy with brain aging changes among HIV-infected adults.

Antiretroviral therapy (ART) is currently recommended for all persons living with HIV (PLWH), regardless of their CD4 T-cell count, and should be continued throughout life. Nonetheless, vigilance of the safety of ART, including its neurotoxicity, must continue. We hypothesized that use of certain ART drugs might be associated with aging-related cerebral degenerative changes among PLWH. Clinicopathological study of PLWH who were using ART drugs at the last clinical assessment. Using multivariable logistic regression, we tested associations between use of each specific ART drug (with reference to use of other ART drugs) and cerebral degenerative changes including neuronal phospho-tau lesions, β-amyloid plaque deposition, microgliosis, and astrogliosis in the frontal cortex and putamen (immunohistochemistry), as well as cerebral small vessel disease (CSVD) in the forebrain white matter (standard histopathology), with relevant covariates being taken into account. The Bonferroni adjustment was applied. Darunavir use was associated with higher likelihood of neuronal phospho-tau lesions in the putamen [odds ratio (OR) 15.33, n = 93, P = 0.005]. Ritonavir use was associated with marked microgliosis in the putamen (OR 4.96, n = 101, P = 0.023). On the other hand, use of tenofovir disoproxil fumarate was associated with lower likelihood of β-amyloid plaque deposition in the frontal cortex (OR 0.13, n = 102, P = 0.012). There was a trend toward an association between emtricitabine use and CSVD (OR 13.64, n = 75, P = 0.099). Our findings suggest that PLWH treated with darunavir and ritonavir may be at increased risk of aging-related cerebral degenerative changes.

Effect of anti-retroviral therapy on oxidative stress in hospitalized HIV-infected adults with and without TB.

HIV infection and opportunistic infections cause oxidative stress (OS), which is associated with tissue damage. Anti-retroviral therapy (ART) is used to treat HIV and decrease the risk of opportunistic infections, but it is unclear whether ART reduces OS. Association of ART with OS was investigated. We stratified a convenience sample of frozen serum or plasma from HIV-infected, ART-naïve (n=21); HIV-infected, ART-treated (n=14); HIV and PTB co-infected, ART-naïve (n=21); HIV and PTB co-infected, ART-treated (n=25) patients. Controls (n=21) were HIV-negative adults without TB symptoms. Concentration of OS markers namely: transaminases (ALT and AST), gamma glutamyl transpeptidase (GGT), albumin, total protein, malondialdehyde (MDA), vitamin C, and total anti-oxidant status (TAS) were determined. AST (p<0.001), GGT (p<0.001), total protein (p=0.001) and MDA (p<0.001) were higher in HIV patients compared to controls. Vitamin C (P<0.0001) and albumin (p<0.01) were lower in HIV-patients relative to controls. ART was only associated with higher albumin (p=0.001), higher GGT (p=0.02) and lower vitamin C (p=0.009). HIV and PTB co-infection was only significantly associated with higher GGT (p=0.01) and AST (p=0.03). We identified severe OS among HIV-patients. ART was associated with both increased and reduced markers of OS hence suggesting that ART may not attenuate OS.

Association of antiretroviral therapy with high-risk human papillomavirus, cervical intraepithelial neoplasia, and invasive cervical cancer in women living with HIV: a systematic review and meta-analysis

SummaryBackgroundThe interactions between antiretroviral therapy (ART) and high-risk human papillomavirus (HPV) and cervical lesions in women living with HIV are poorly understood. We reviewed the association of ART with these outcomes.MethodsWe did a systematic review and meta-analysis by searching MEDLINE and Embase databases for cross-sectional or cohort studies published in English between Jan 1, 1996, and May 6, 2017, which reported the association of ART with prevalence of high-risk HPV or prevalence, incidence, progression, or regression of histological or cytological cervical abnormalities, or incidence of invasive cervcal cancer. Studies were eligible if they reported the association of combination ART or highly active ART use with the following outcomes: high-risk HPV prevalence; squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) prevalence, incidence, progression, or regression; and invasive cervical cancer incidence among women living with HIV. We did random-effects meta-analyses to estimate summary statistics. We examined heterogeneity with the I2 statistic. This review is registered on the PROSPERO database at the Centre of Reviews and Dissemination, University of York, York, UK (registration number CRD42016039546).FindingsWe identified 31 studies of the association of ART with prevalence of high-risk HPV (6537 women living with HIV) and high grade cervical lesions (HSIL-CIN2+; 9288 women living with HIV). Women living with HIV on ART had lower prevalence of high-risk HPV than did those not on ART (adjusted odds ratio [aOR] 0·83, 95% CI 0·70–0·99; I2=51%, adjusted for CD4 cell count and ART duration), and there was some evidence of association with HSIL-CIN2+ (0·65, 0·40–1·06; I2=30%). 17 studies reported the association of ART with longitudinal cervical lesion outcomes. ART was associated with a decreased risk of HSIL-CIN2+ incidence among 1830 women living with HIV (0·59, 0·40–0·87; I2=0%), SIL progression among 6212 women living with HIV (adjusted hazard ratio [aHR] 0·64, 95% CI 0·54–0·75; I2=18%), and increased likelihood of SIL or CIN regression among 5261 women living with HIV (1·54, 1·30–1·82; I2=0%). In three studies among 15 846 women living with HIV, ART was associated with a reduction in invasive cervical cancer incidence (crude HR 0·40, 95% CI 0·18–0·87, I2=33%).InterpretationEarly ART initiation and sustained adherence is likely to reduce incidence and progression of SIL and CIN and ultimately incidence of invasive cervical cancer. Future cohort studies should aim to confirm this possible effect.FundingUK Medical Research Council.

Associations Between Antiretroviral Treatment and Avascular Bone Necrosis: The Swiss HIV Cohort Study.

BackgroundHIV-infected individuals have an increased risk of avascular bone necrosis (AVN). Antiretroviral therapy (ART) and particularly protease inhibitors (PI) have been implicated as a risk factor. We aimed to study the associations of ART with the occurrence of AVN among Swiss HIV Cohort Study participants (SHCS).MethodsWe used incidence density sampling to perform a case control study within the Swiss HIV Cohort Study (SHCS) comparing prospectively collected AVN cases and controls by conditional logistic regression analysis. To evaluate the effect of ART, multivariable models were adjusted for HIV transmission risk group, age, alcohol consumption, use of corticosteroids, CD4 nadir, maximum viral load, and pancreatitis.ResultsWe compared 74 AVN cases and 145 controls. Associations with AVN were shown for heterosexual HIV acquisition (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.1–10), alcohol consumption (OR, 2.7; 95% CI, 1.3–5.7), and hyperlipidemia (OR, 3.6; 95% CI, 1.4–9.6). After adding ART substances to the multivariable base model, there was evidence of an association for treatment with tenofovir (TDF) >1 year (OR, 4.4; 95% CI, 1.4–14) with AVN. Neither exposure to specific frequently prescribed ART combinations or ART drug classes nor cumulative ART exposure showed any associations with AVN.ConclusionsIn the HIV-infected population, a combination of risk factors such as heterosexual HIV acquisition, moderate to severe alcohol intake, and hyperlipidemia seem to contribute to AVN. ART does not seem to be a relevant risk factor for AVN. The association of prolonged TDF exposure with AVN needs to be confirmed.

Is there sufficient evidence for a causal association between antiretroviral therapy and diabetes in HIV-infected patients? A meta-analysis.

The association of antiretroviral therapy (ART) with diabetes is inconsistent and varies widely across primary epidemiological studies. A comprehensive and more precise estimate of this association is fundamental to establishing a plausible causal link between ART and diabetes. We identified epidemiological studies that compared mean fasting plasma glucose (FPG) concentrations and proportions of diabetes and metabolic syndrome between HIV-infected patients naïve and exposed to ART. Mean difference in FPG concentrations and odds ratios of diabetes and metabolic syndrome were pooled using random-effects meta-analyses. Data on 20178 participants from 41 observational studies were included in the meta-analyses. Mean FPG concentrations (Pooled mean difference: 4.66mg/dL; 95% confidence interval [CI], 2.52 to 6.80; 24 studies) and the odds of diabetes (Pooled odds ratios: 3.85; 95% CI, 2.93 to 5.07; 10 studies) and metabolic syndrome (Pooled odds ratios: 1.45; 95% CI, 1.03 to 2.03; 18 studies) were significantly higher among ART-exposed patients, compared to their naïve counterparts. ART was also associated with significant increases in FPG levels in studies with mean ART duration ≥18months (Pooled mean difference: 4.97mg/dL; 95% CI, 3.10 to 6.84; 14 studies), but not in studies with mean ART duration <18months (Pooled mean difference: 4.40mg/dL, 95% CI, -0.59 to 9.38; 7 studies). ART may potentially be the single most consistent determinant of diabetes in people living with HIV worldwide. However, given the preponderance of cross-sectional studies in the meta-analysis, the association between ART and diabetes cannot be interpreted as cause and effect.

Relationship Between HIV Infection, Antiretroviral Therapy, Inflammatory Markers, and Cerebrovascular Endothelial Function Among Adults in Urban China.

Cerebrovascular risk is increased in people living with HIV infection compared with age-matched uninfected individuals. Cerebrovascular endothelial dysfunction related to antiretroviral therapy (ART) and inflammation may contribute to higher stroke risk in HIV infection. We compared cerebral vasoreactivity-a measure of cerebrovascular endothelial function assessed by the breath-holding index (BHI) using transcranial Doppler ultrasound-between virologically suppressed Chinese HIV-infected individuals followed in an HIV clinic in Beijing, China, and uninfected controls. We constructed mixed-effects models to evaluate the association of HIV, ART, and inflammatory markers with cerebral vasoreactivity. In an unadjusted model, HIV infection was associated with a trend toward lower cerebral vasoreactivity (BHI 1.08 versus 1.26, P = 0.079). In multivariable analyses, cholesterol modified the association between HIV infection and cerebral vasoreactivity (P = 0.015 for interaction). At a lower total cholesterol of 4.15 mmol/L, HIV was associated with lower cerebral vasoreactivity (BHI -0.28, P = 0.019), whereas at a cholesterol of 5.15 mmol/L, the reduction in cerebral vasoreactivity associated with HIV was no longer statistically significant (BHI -0.05, P = 0.64). Among HIV-infected individuals, use of lopinavir/ritonavir compared with efavirenz was associated with lower cerebral vasoreactivity (BHI -0.24, P = 0.040). We did not find a significant association between inflammatory markers and cerebral vasoreactivity. Cerebrovascular endothelial dysfunction associated with HIV infection may be most relevant for individuals with less traditional vascular risk, such as those with lower cholesterol. Further study of the impact of ART on cerebrovascular endothelial function is warranted to aid with ART selection in individuals at high cerebrovascular risk.