Browsing by Subject "Anti-Retroviral Agents"
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Item Open Access CD4 enumeration technologies: a systematic review of test performance for determining eligibility for antiretroviral therapy.(PLoS One, 2015) Peeling, Rosanna W; Sollis, Kimberly A; Glover, Sarah; Crowe, Suzanne M; Landay, Alan L; Cheng, Ben; Barnett, David; Denny, Thomas N; Spira, Thomas J; Stevens, Wendy S; Crowley, Siobhan; Essajee, Shaffiq; Vitoria, Marco; Ford, NathanBACKGROUND: Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. METHODS AND FINDINGS: Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/μl, bias ranged from -35.2 to +13.1 cells/μl while at counts >350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. CONCLUSIONS: A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed.Item Open Access Effective treatment of SIVcpz-induced immunodeficiency in a captive western chimpanzee.(Retrovirology, 2017-06-02) Barbian, Hannah J; Jackson-Jewett, Raven; Brown, Corrine S; Bibollet-Ruche, Frederic; Learn, Gerald H; Decker, Timothy; Kreider, Edward F; Li, Yingying; Denny, Thomas N; Sharp, Paul M; Shaw, George M; Lifson, Jeffrey; Acosta, Edward P; Saag, Michael S; Bar, Katharine J; Hahn, Beatrice HSimian immunodeficiency virus of chimpanzees (SIVcpz), the progenitor of human immunodeficiency virus type 1 (HIV-1), is associated with increased mortality and AIDS-like immunopathology in wild-living chimpanzees (Pan troglodytes). Surprisingly, however, similar findings have not been reported for chimpanzees experimentally infected with SIVcpz in captivity, raising questions about the intrinsic pathogenicity of this lentivirus.Here, we report progressive immunodeficiency and clinical disease in a captive western chimpanzee (P. t. verus) infected twenty years ago by intrarectal inoculation with an SIVcpz strain (ANT) from a wild-caught eastern chimpanzee (P. t. schweinfurthii). With sustained plasma viral loads of 105 to 106 RNA copies/ml for the past 15 years, this chimpanzee developed CD4+ T cell depletion (220 cells/μl), thrombocytopenia (90,000 platelets/μl), and persistent soft tissue infections refractory to antibacterial therapy. Combination antiretroviral therapy consisting of emtricitabine (FTC), tenofovir disoproxil fumarate (TDF), and dolutegravir (DTG) decreased plasma viremia to undetectable levels (<200 copies/ml), improved CD4+ T cell counts (509 cell/μl), and resulted in the rapid resolution of all soft tissue infections. However, initial lack of adherence and/or differences in pharmacokinetics led to low plasma drug concentrations, which resulted in transient rebound viremia and the emergence of FTC resistance mutations (M184V/I) identical to those observed in HIV-1 infected humans.These data demonstrate that SIVcpz can cause immunodeficiency and other hallmarks of AIDS in captive chimpanzees, including P. t. verus apes that are not naturally infected with this virus. Moreover, SIVcpz-associated immunodeficiency can be effectively treated with antiretroviral therapy, although sufficiently high plasma concentrations must be maintained to prevent the emergence of drug resistance. These findings extend a growing body of evidence documenting the immunopathogenicity of SIVcpz and suggest that experimentally infected chimpanzees may benefit from clinical monitoring and therapeutic intervention.Item Open Access Improved tuberculosis outcomes with daily vs. intermittent rifabutin in HIV-TB coinfected patients in India.(The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2016-09) Jenks, JD; Kumarasamy, N; Ezhilarasi, C; Poongulali, S; Ambrose, P; Yepthomi, T; Devaraj, C; Benson, CASetting
Y R Gaitonde Centre for AIDS Research and Education, Chennai, India.Objective
To compare anti-tuberculosis treatment outcomes in individuals with human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection on atazanavir/ritonavir (ATV/r) antiretroviral therapy (ART) plus daily rifabutin (RBT) 150 mg with those on ATV/r plus thrice-weekly RBT 150 mg.Design
A retrospective study was conducted of two HIV-TB co-infected cohorts between 2003 and 2014. Basic demographic and TB outcome data were obtained from an electronic database and patient records. The χ(2) and Fisher's exact test were used to compare daily and intermittent RBT treatment groups.Results
Of 292 individuals on an ATV/r-based ART regimen plus RBT, 118 (40.4%) received thrice-weekly RBT and 174 (59.6%) daily RBT. Patients in the two RBT treatment groups were similar in sex, age, previous history of TB, site of TB and acid-fast bacilli smear status. More individuals in the daily vs. the intermittent RBT group achieved clinical cure (73.0% vs. 44.1%, P < 0.001), with no significant differences in relapse/recurrence or all-cause mortality between groups.Conclusion
There were higher rates of clinical TB cure in individuals on a boosted protease inhibitor-based ART regimen with daily RBT compared to intermittently dosed RBT. Optimal RBT dosing in this setting requires further investigation.Item Open Access Influence of HLA-C expression level on HIV control.(Science, 2013-04-05) Apps, Richard; Qi, Ying; Carlson, Jonathan M; Chen, Haoyan; Gao, Xiaojiang; Thomas, Rasmi; Yuki, Yuko; Del Prete, Greg Q; Goulder, Philip; Brumme, Zabrina L; Brumme, Chanson J; John, Mina; Mallal, Simon; Nelson, George; Bosch, Ronald; Heckerman, David; Stein, Judy L; Soderberg, Kelly A; Moody, M Anthony; Denny, Thomas N; Zeng, Xue; Fang, Jingyuan; Moffett, Ashley; Lifson, Jeffrey D; Goedert, James J; Buchbinder, Susan; Kirk, Gregory D; Fellay, Jacques; McLaren, Paul; Deeks, Steven G; Pereyra, Florencia; Walker, Bruce; Michael, Nelson L; Weintrob, Amy; Wolinsky, Steven; Liao, Wilson; Carrington, MaryA variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease.Item Open Access Postnatal cytomegalovirus exposure in infants of antiretroviral-treated and untreated HIV-infected mothers.(Infect Dis Obstet Gynecol, 2014) Meyer, Sarah A; Westreich, Daniel J; Patel, Emily; Ehlinger, Elizabeth P; Kalilani, Linda; Lovingood, Rachel V; Denny, Thomas N; Swamy, Geeta K; Permar, Sallie RHIV-1 and CMV are important pathogens transmitted via breastfeeding. Furthermore, perinatal CMV transmission may impact growth and disease progression in HIV-exposed infants. Although maternal antiretroviral therapy reduces milk HIV-1 RNA load and postnatal transmission, its impact on milk CMV load is unclear. We examined the relationship between milk CMV and HIV-1 load (4-6 weeks postpartum) and the impact of antiretroviral treatment in 69 HIV-infected, lactating Malawian women and assessed the relationship between milk CMV load and postnatal growth in HIV-exposed, breastfed infants through six months of age. Despite an association between milk HIV-1 RNA and CMV DNA load (0.39 log(10) rise CMV load per log(10) rise HIV-1 RNA load, 95% CI 0.13-0.66), milk CMV load was similar in antiretroviral-treated and untreated women. Higher milk CMV load was associated with lower length-for-age (-0.53, 95% CI: -0.96, -0.10) and weight-for-age (-0.40, 95% CI: -0.67, -0.13) Z-score at six months in exposed, uninfected infants. As the impact of maternal antiretroviral therapy on the magnitude of postnatal CMV exposure may be limited, our findings of an inverse relationship between infant growth and milk CMV load highlight the importance of defining the role of perinatal CMV exposure on growth faltering of HIV-exposed infants.Item Open Access Predicting virologic failure among HIV-1-infected children receiving antiretroviral therapy in Tanzania: a cross-sectional study.(J Acquir Immune Defic Syndr, 2010-08) Emmett, Susan D; Cunningham, Coleen K; Mmbaga, Blandina T; Kinabo, Grace D; Schimana, Werner; Swai, Mark E; Bartlett, John A; Crump, John A; Reddy, Elizabeth ABACKGROUND: Many HIV care and treatment programs in resource-limited settings rely on clinical and immunologic monitoring of antiretroviral therapy (ART), but accuracy of this strategy to detect virologic failure (VF) among children has not been evaluated. METHODS: A cross-sectional sample of HIV-infected children aged 1-16 years on ART >or=6 months receiving care at a Tanzanian referral center underwent clinical staging, CD4 lymphocyte measurement, plasma HIV-1 RNA level, and complete blood count. Associations with VF (HIV-1 RNA >or=400 copies/mL) were determined utilizing bivariable and multivariate analyses; accuracy of current clinical and immunologic guidelines in identifying children with VF was assessed. FINDINGS: Of 206 children (median age 8.7 years, ART duration 2.4 years), 65 (31.6%) demonstrated VF at enrollment. Clinical and immunological criteria identified 2 (3.5%) of 57 children with VF on first-line therapy, exhibiting 3.5% sensitivity and 100% specificity. VF was associated with younger age, receipt of nevirapine vs. efavirenz-based regimen, CD4% < 25%, and physician documentation of maladherence (P < 0.05 on bivariable analysis); the latter 2 factors remained significant on multivariate logistic regression. INTERPRETATION: This study demonstrates poor performance of clinical and immunologic criteria in identifying children with virologic failure. Affordable techniques for measuring HIV-1 RNA level applicable in resource-limited settings are urgently needed.Item Open Access Prenatal protease inhibitor use and risk of preterm birth among HIV-infected women initiating antiretroviral drugs during pregnancy.(J Infect Dis, 2010-04-01) Patel, Kunjal; Shapiro, David E; Brogly, Susan B; Livingston, Elizabeth G; Stek, Alice M; Bardeguez, Arlene D; Tuomala, Ruth E; P1025 team of the International Maternal Pediatric Adolescent AIDS Clinical Trials GroupBACKGROUND: Conflicting results have been reported among studies of protease inhibitor (PI) use during pregnancy and preterm birth. Uncontrolled confounding by indication may explain some of the differences among studies. METHODS: In total, 777 human immunodeficiency virus (HIV)-infected pregnant women in a prospective cohort who were not receiving antiretroviral (ARV) treatment at conception were studied. Births <37 weeks gestation were reviewed, and deliveries due to spontaneous labor and/or rupture of membranes were identified. Risk of preterm birth and low birth weight (<2500 g) were evaluated by using multivariable logistic regression. RESULTS: Of the study population, 558 (72%) received combination ARV with PI during pregnancy, and a total of 130 preterm births were observed. In adjusted analyses, combination ARV with PI was not significantly associated with spontaneous preterm birth, compared to ARV without PI (odds ratio [OR], 1.22; 95% confidence interval [CI], 0.70-2.12). Sensitivity analyses that included women who received ARV prior to pregnancy also did not identify a significant association (OR, 1.34; 95% CI, 0.84-2.16). Low birth weight results were similar. CONCLUSIONS: No evidence of an association between use of combination ARV with PI during pregnancy and preterm birth was found. Our study supports current guidelines that promote consideration of combination ARV for all HIV-infected pregnant women.Item Open Access Systemic lupus erythematosus and HIV infection: a whimsical relationship. Reports of two cases and review of the literature.(Clinical rheumatology, 2013-09) Carugati, Manuela; Franzetti, Marco; Torre, Alessandro; Giorgi, Riccardo; Genderini, Augusto; Strambio de Castilla, Francesco; Gervasoni, Cristina; Riva, AgostinoUnlabelled
Systemic lupus erythematosus (SLE) is rarely reported in association with HIV infection. We describe two unpredictable cases and provide a review of the literature. Retrospective analysis of the medical records of two HIV-infected patients diagnosed with SLE and admitted at Luigi Sacco Hospital (Milano, Italy). Search of the literature from 1981 to 2012 and review of the cases reported. Case 1: a 32-year-old HIV-infected African woman who developed a SLE flare after re-introduction of antiretroviral therapy (ART). The flare was characterized by bullous skin eruption and membranous glomerulonephritis. Case 2: a 44-year-old Caucasian woman, admitted to our hospital because of lacunar stroke: HIV infection and SLE were simultaneously diagnosed.Literature
55 cases of SLE in the setting of HIV infection were reported. Forty-five patients met the requirements of the American College of Rheumatology for the diagnosis of SLE. The diagnosis of SLE preceded HIV infection in six patients. On the contrary, in 29 patients, HIV infection was reported before SLE. Median CD4+ count at SLE diagnosis was 361 cells/μl. A SLE manifestation following ART immune recovery was documented in 18.2% of the cases. On the contrary, the progression of HIV infection paralleled with SLE remission in 22.5% of the patients. The study shows that an autoimmune disease such as SLE can occur despite the loss of immunocompetence caused by HIV infection. Moreover, SLE and HIV infection influence each other possibly through immunologic mechanisms determining awkward manifestations.