Background How coinfection with hepatitis C virus (HCV) impacts on the trajectory of kidney function in human immunodeficiency virus (HIV)-infected patients is unclear. This study examined the effect ...of HCV infection on kidney function over time in women infected with HIV. Study Design Retrospective observational cohort. Setting & Participants Study sample included participants from the Women's Interagency HIV Study who were HIV infected and had undergone HCV antibody testing and serum creatinine measurement at baseline. Predictor HCV seropositivity. Outcomes & Measurement Estimated glomerular filtration rate (eGFR) calculated from semi-annual serum creatinine measurements using the 4-variable Modification of Diet in Renal Diseases (MDRD) Study equation. Linear mixed models were used to evaluate the independent effect of HCV seropositivity on eGFR over time, adjusting for demographic factors, comorbid conditions, illicit drug use, measures of HIV disease status, use of medications, and interactions with baseline low eGFR (<60 mL/min/1.73 m2 ). Results Of 2,684 HIV-infected women, 952 (35%) were found to be HCV seropositive. In 180 women with chronic kidney disease (CKD) at baseline (eGFR < 60 mL/min/1.73 m2 ), HCV seropositivity was independently associated with a fully adjusted net decrease in eGFR of approximately 5% per year (95% confidence interval, 3.2 to 7.2) relative to women who were seronegative. In contrast, HCV infection was not independently associated with a decrease in eGFR in women without low eGFR at baseline ( P < 0.001 for interaction). Limitations The MDRD Study equation has not been validated as a measure of GFR in persons with HIV or HCV infection. Proteinuria was not included in the study analysis. Because the study is observational, effects of residual confounding cannot be excluded. Conclusions In HIV-infected women with CKD, coinfection with HCV is associated with a modest, but statistically significant, decrease in eGFR over time. More careful monitoring of kidney function may be warranted for HIV-infected patients with CKD who are also coinfected with HCV.
BACKGROUND:Recent studies reported that the CD4/CD8 T-cell ratio is inversely associated with biomarkers traditionally used to measure immune activation and systemic inflammation in highly active ...antiretroviral therapy–treated HIV-infected (HIV+) patients. The relation of hepatitis C virus (HCV) coinfection with the CD4/CD8 ratio in HIV+ patients is unknown.
METHODS:We examined 50,201 CD4/CD8 ratios measured over 20 years in 3 groups of HIV+ women enrolled in the Womenʼs Interagency HIV StudyHCV antibody negative (n = 1734), cleared HCV (n = 231), and chronic HCV (n = 751) in multivariate models. IFNL4-ΔG genotype and HCV viral load were also considered.
RESULTS:Compared with HCV antibody negative status, chronic HCV infection was associated with lower CD4/CD8 ratios when HIV viral load was suppressed to the lower limit of quantification (β = −0.08; P = 0.002). Cleared HCV (β = −0.10; P = 0.0009), but not IFNL4-ΔG genotype or HCV viral load, was also associated with lower CD4/CD8 ratios when HIV viral load was suppressed to the lower limit of quantification.
CONCLUSIONS:The association of HCV coinfection with CD4/CD8 ratio is consistent with previously observed associations of HCV coinfection with biomarkers traditionally used to measure immune activation and systemic inflammation in HIV+ patients. These data provide additional support for the use of CD4/CD8 ratio for routine monitoring of immune activation and inflammation in HIV+ patients, including those with HIV/HCV coinfection; however, the unexpected association between cleared HCV and lower CD4/CD8 ratio requires additional study.
Abstract
Background
Integrase strand-transfer inhibitors (INSTIs) are associated with body weight gain among women living with HIV (WLH) in the Women’s Interagency HIV Study (WIHS). The role of ...antiretroviral therapy (ART) pharmacokinetics in INSTI-associated weight gain is unknown. We report the relationship between INSTI plasma concentrations and weight change in WLH.
Model-adjusted estimates of percent body weight change by integrase inhibitor plasma concentration
Model-adjusted estimates of percent body weight change with 95% confidence band (y-axis) by integrase inhibitor plasma concentration in ng/mL (x-axis). Models were adjusted for baseline age, race/ethnicity, baseline obesity (body mass index ≥ 30 kg/m2), history of prior non-nucleoside reverse transcriptase use, and self-reported antiretroviral therapy adherence (100% vs <100%). Abbreviations: RAL=raltegravir, DTG=dolutegravir, EVG=elvitegravir
Methods
Data from 2006-2017 were analyzed from virologically suppressed (< 200 copies/mL) WLH in the WIHS who switched/added raltegravir (RAL), dolutegravir (DTG), or elvitegravir (EVG) to ART. Percent body weight change was calculated using weights obtained 6-12 months pre- and post- INSTI switch/add. INSTI random plasma concentrations were measured with validated LC/MS-MS assays 6-12 months post INSTI switch/add. Area under the curve (AUC) was calculated using estimates from published models and updating individual-level parameters with plasma concentrations. Linear models assessed the relationship between plasma concentrations or AUC and weight change for each INSTI separately. Models were adjusted for age, race/ethnicity, baseline obesity, history of non-nucleoside reverse transcriptase use, and self-reported ART adherence.
Results
176 WLH contributed plasma drug concentrations with a mean ±SD 1.5 (±0.1) years follow-up: 43 (24%) were on RAL, 87 (49%) on DTG, and 47 (27%) on EVG. Mean age was 51 years (± 9), 64% were Non-Hispanic Black, baseline BMI was 31.6 kg/m2 (±8.8), and 57% reported 100% ART adherence. Mean percent body weight change was +2.3% (±6.0) for RAL, +1.8% (±9.0) for DTG, and +2.8% (±10.5) for EVG. AUC was able to be calculated in 167 (95%) of women. In adjusted linear models, higher RAL plasma concentration was associated with greater percent body weight change (p=0.016), Figure 1. No association of drug AUC with body weight change for any INSTI was observed.
Conclusion
In WLH, random RAL plasma concentrations, but not the RAL AUC, was associated with body weight gain. In contrast, the effect of DTG and EVG plasma drug exposure on short-term body weight change appears to be limited. Mechanisms contributing to body weight gain may be INSTI-specific. In addition to further pharmacologic assessments, other mechanisms to explain INSTI-associated weight gain should be examined.
Disclosures
Cecile D. Lahiri, MD, MS, Merck: Grant/Research Support|Theratechnologies, LLC: Advisor/Consultant|Theratechnologies, LLC: Honoraria Julie B. Dumond, PharmD, Merck: Grant/Research Support Cyra Christina Mehta, PhD, MSPH, Merck: Grant/Research Support Igho Ofotokun, MD, MSc, FIDSA, Merck: Grant/Research Support Maria L L. Alcaide, MD, Discidium Biosciences: Board Member|Gilead: Honoraria|Merk & Co: Honoraria|Senhwa Biosciences: Honoraria|Virology Education: Honoraria Jordan Lake, MD, Gilead Sciences: Grant/Research Support|Theratechnologies: Advisor/Consultant Phyllis C. Tien, MD, MSc, Merck: Grant/Research Support
Antiretroviral therapy for pregnant women Minkoff, Howard; Augenbraun, Michael
American journal of obstetrics and gynecology,
02/1997, Letnik:
176, Številka:
2
Journal Article
Recenzirano
Reproductive-age women constitute an increasing percentage of individuals infected with human immunodeficiency virus. As clinical management issues particular to pregnancy become increasingly common, ...they are also becoming increasingly complex. With the approval of new antiretroviral agents, monotherapy with zidovudine, although still standard for prevention of mother-to-child transmission of human immunodeficiency virus, has become inadequate therapy for treatment of the mother. Clinicians must now consider alternative therapeutic strategies in spite of a dearth of experience in the setting of pregnancy. To facilitate optimal drug treatment of human immunodeficiency virus–infected pregnant women while maintaining a focus on prevention of transmission, we reviewed Medline, Reprotox, personal files, and pharmaceutical industry information about the antiretroviral agents currently approved. After summarizing potential beneficial and detrimental effects in both the pregnant and nonpregnant individual, we suggest clinical strategies and discuss the ethical and legal principles that should guide therapeutic decisions in pregnancy.(Am J Obstet Gynecol 1997;176:478-89.)
Individuals with HIV infection exhibit high cytomegalovirus (CMV) IgG levels, but there are few data regarding the association of hepatitis C virus (HCV) with the immune response against CMV.
...Associations of HCV with CMV seropositivity and CMV IgG levels were studied in 635 HIV-infected women, 187 of whom were HCV-seropositive, with adjustment in multivariable models for age, race/ethnicity, and HIV disease characteristics. Eighty one percent of the women reported receipt of highly active antiretroviral therapy (HAART) prior to or at CMV testing.
In adjusted models women with chronic HCV had higher CMV IgG levels than those without HCV RNA (β = 2.86, 95% CI:0.89 - 4.83; P = 0.004). The association of HCV RNA with CMV IgG differed by age (P(interaction) = 0.0007), with a strong association observed among women in the low and middle age tertiles (≤ 45.3 years of age; β = 6.21, 95% CI:3.30 - 9.11, P<0.0001) but not among women in the high age tertile. CMV IgG levels were not associated with non-invasive measures of liver disease, APRI and FIB-4, or with HCV RNA level and adjustment for Epstein-Barr virus (EBV) IgG levels did not affect the association between HCV and CMV.
CMV IgG levels are higher in HCV/HIV co-infected women than in HIV mono-infected women. Further research on the association of HCV with CMV IgG is indicated because prior studies have found CMV IgG to be associated with morbidity and mortality in the general population and subclinical carotid artery disease in HIV-infected patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Opiate use is common in HIV-infected and hepatitis C virus (HCV)-infected individuals, however, its contribution to the risk of diabetes mellitus is not well understood.
Prospective study of 1713 ...HIV-infected and 652 HIV-uninfected participants from the Women's Interagency HIV Study between October 2000 and March 2006. Diabetes defined as fasting glucose > or =126 mg/dL, self report of diabetes medication use, or confirmed diabetes diagnosis. Opiate use determined using an interviewer-administered questionnaire. Detectable plasma HCV RNA confirmed HCV infection.
Current opiate users had a higher prevalence of diabetes (15%) than nonusers (10%, P = 0.03), and a higher risk of incident diabetes (adjusted relative hazard: 1.58, 95% confidence interval: 1.01 to 2.46), after controlling for HCV infection, HIV/antiretroviral therapy status, and diabetes risk factors including age, race/ethnicity, family history of diabetes, and body mass index. HCV infection was also an independent risk factor for diabetes (adjusted relative hazard: 1.61, 95% confidence interval: 1.02 to 2.52). HCV-infected women reporting current opiate use had the highest diabetes incidence (4.83 cases per 100 person-years).
Among women with or at-risk for HIV, opiate use is associated with increased diabetes risk independently of HCV infection. Diabetic screening should be part of care for opiate users and those infected with HCV.
Management of Chronic Urethral Symptoms in Men Augenbraun, Michael H.; Cummings, Marinella; McCormack, William M.
Clinical infectious diseases,
10/1992, Letnik:
15, Številka:
4
Journal Article
Recenzirano
We describe 20 men who were referred because of chronic urogenital symptoms. They had been previously seen by zero to six physicians (mean, 1.8 physicians) and had been treated with zero to five ...courses of antimicrobial agents (mean, 2.4 courses) without relief of their symptoms. Results of physical examinations of all patients were normal. An extensive evaluation failed to reveal any objective evidence of urethral inflammation. Cultures for Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum, and Trichomonas vaginalis were uniformly negative. No additional antimicrobial agents were prescribed. Data from follow-up questionnaires filled out by 10 of these men 5–28 months later (mean, 11.8 months) disclosed the disappearance of symptoms in three and the reduction of symptoms in four. Chronic urethral symptoms may occur in the absence of objective evidence of inflammation and infection with known urethral pathogens. Observation without antimicrobial therapy is the treatment of choice for such patients.
OBJECTIVETo estimate the incidence of lipoatrophy and lipohypertrophy among HIV-infected and HIV-uninfected women from the Women's Interagency HIV Study.
DESIGNEight hundred fifteen women with ...semiannual data on self-report of bidirectional change in body fat, anthropometric measurements, weight, and bioelectric impedance analysis were included in a 30-month incidence analysis.
METHODSLipoatrophy and lipohypertrophy in both peripheral (arms, legs, and buttocks) and central (waist, chest, and upper back) sites were defined by self-report of either a decrease or an increase in a body fat region over the previous 6 months that was confirmed by a corresponding change in anthropometric measurement.
RESULTSWeight and total body fat increased in HIV-uninfected women but remained stable in HIV-infected women over 30 months. Among HIV-infected women, the incidence of peripheral (relative hazard, 2.1; 95% confidence interval CI, 1.4–3.3) and central (relative hazard, 1.9; 95% CI, 1.2–2.8) lipoatrophy was about double that among HIV-uninfected women, after adjustment for age and race. The incidence of peripheral lipohypertrophy appeared lower among HIV-infected women than among HIV-uninfected women (relative hazard, 0.8; 95% CI, 0.6–1.1), while the incidence of central lipohypertrophy did not differ by HIV status. Of HIV-infected women with 2 of 4 lipodystrophy outcomes, most (81%) had combined peripheral and central lipoatrophy or combined peripheral and central lipohypertrophy. Only 14% of these women had both peripheral lipoatrophy and central lipohypertrophy
CONCLUSIONSThese prospective data suggest that lipoatrophy, affecting both peripheral and central sites, predominates in HIV-infected women. The simultaneous occurrence of peripheral lipoatrophy and central lipohypertrophy was uncommon.
It appears incontestable that there is a link between genital ulcer disease and HIV infection. On the one hand the natural history and response to therapy of syphilis, HSV-2, and chancroid are all ...modified by the immunosuppressive effects of HIV infection. On the other hand, HIV transmission is probably facilitated by the disruption of the normal epithelial barriers of the genital organs caused by these ulcerative infections. Information is somewhat less convincing that a similar association exists between the nonulcerative STDs (trichomonas, gonorrhea, chlamydial infections) and HIV. Conceptually, the mucosal inflammation associated with these infections might serve as a focus for HIV transmission. The available data, though suggestive, do not strongly support this contention. Theoretically though, even a small risk might potentially result in significant HIV transmission given the prevalence of nonulcerative STDs. These infectious processes do not appear to be markedly altered by HIV induced immunosuppression. The ability of HPV to cause dysplastic changes in cervical and anal tissue did not require the AIDS epidemic to come to light. In HIV infection, disruptions of immunoregulatory processes, which might ordinarily control the progression of potentially malignant cell lines, have created fertile ground for an increasing incidence of premalignant and malignant cytologic changes. The mutual impact these processes have or may have on one another requires that clinicians who care for patients with either HIV infection or with STDs should be thoroughly familiar with both and not consider them somehow exclusive of one another. Efforts toward the prevention and control of STDs should be considered important in the control and prevention of HIV transmission.
In HIV negatives, markers of hemostasis, including D-dimer, factor VIII, plasminogen activator inhibitor-1 antigen (PAI-1), and total protein S are associated with all-cause and cardiovascular ...disease mortality. In HIV positives, studies of D-dimer and factor VIII with death were limited to short follow-up; associations of PAI-1 and total protein S with death have not been examined. In 674 HIV-infected women from the Womenʼs Interagency HIV Study, markers from the first visit after enrollment were exposures of interest in multivariate analyses of death (AIDS and non-AIDS) in separate models at 5 and 16 years. There were 87 AIDS and 44 non-AIDS deaths at 5 years, and 159 AIDS and 113 non-AIDS deaths at 16 years. An inverse association of total protein S quartiles with non-AIDS deaths was observed at 5 (P trend = 0.002) and 16 years (P trend = 0.02); there was no association with AIDS deaths. The third quartile of PAI-1 was associated with AIDS deaths at 5 hazard ratio (HR) = 4.0; 95% confidence interval (CI)1.9 to 8.4 and 16 years (HR = 3.4; 95% CI1.9 to 5.9); and with non-AIDS deaths at 5 years (HR = 4.8; 95% CI1.6 to 13.9). D-dimer and factor VIII were not associated with AIDS or non-AIDS death at 5 or 16 years. Lower total Protein S was a consistent marker of non-AIDS death. We found no association between D-dimer with AIDS or non-AIDS death, in contrast to previous studies showing increased short-term (<5 years) mortality, which may represent sex differences or population heterogeneity. Given longer survival on highly active antiretroviral therapy, further studies of these markers are needed to determine their prognostic value.
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