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Lack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional study
Springer Science and Business Media LLC - Tập 7 - Trang 1-6 - 2010
Phumla Z Sinxadi, Jan-Stefan van der Walt, Helen M McIlleron, Motasim Badri, Peter J Smith, Joel A Dave, Naomi S Levitt, Gary Maartens
Stavudine continues to be widely used in resource poor settings despite its toxicity. Our objective was to determine association between plasma stavudine concentrations and lipoatrophy, concentrations of glucose, lactate and triglycerides. Participants were enrolled in a cross-sectional study with lipoatrophy assessment, oral glucose tolerance test, fasting triglycerides, finger prick lactate, and stavudine concentrations. Individual predictions of the area under the concentration curve (AUC) were obtained using a population pharmacokinetic approach. Logistic regression models were fitted to assess the association between stavudine geometric mean ratio > 1 and impaired fasting glucose, impaired glucose tolerance, hyperlactataemia, hypertriglyceridaemia, and lipoatrophy. There were 47 study participants with a median age of 34 years and 83% were women. The median body mass index and waist:hip ratio was 24.5 kg/m2 and 0.85 respectively. The median duration on stavudine treatment was 14.5 months. The prevalence of lipoatrophy, impaired fasting glucose, impaired glucose tolerance, hyperlactataemia, and hypertriglyceridaemia were 34%, 19%, 4%, 32%, and 23% respectively. Estimated median (interquartile range) stavudine AUC was 2191 (1957 to 2712) ng*h/mL. Twenty two participants had stavudine geometric mean ratio >1. Univariate logistic regression analysis showed no association between stavudine geometric mean ratio >1 and impaired fasting glucose (odds ratio (OR) 2.00, 95% CI 0.44 to 9.19), impaired glucose tolerance (OR 1.14, 95% CI 0.07 to 19.42), hyperlactataemia (OR 2.19, 95%CI 0.63 to 7.66), hypertriglyceridaemia (OR 1.75, 95%CI 0.44 to 7.04), and lipoatrophy (OR 0.83, 95% CI 0.25 to 2.79). There was a high prevalence of metabolic complications of stavudine, but these were not associated with plasma stavudine concentrations. Until there is universal access to safer antiretroviral drugs, there is a need for further studies examining the pathogenesis of stavudine-associated toxicities.
Morning free and total testosterone in HIV-infected men: implications for the assessment of hypogonadism
Springer Science and Business Media LLC - - 2014
Anne Monroe, Adrian S. Dobs, Frank J. Palella, Lawrence A. Kingsley, Mallory D. Witt, Todd T. Brown
HIV-1 subtype C predicted co-receptor tropism in Africa: an individual sequence level meta-analysis
Springer Science and Business Media LLC - Tập 17 - Trang 1-16 - 2020
Nontokozo D. Matume, Denis M. Tebit, Pascal O. Bessong
Entry inhibitors, such as Maraviroc, hold promise as components of HIV treatment and/or pre-exposure prophylaxis in Africa. Maraviroc inhibits the interaction between HIV Envelope gp120 V3-loop and CCR5 coreceptor. HIV-1 subtype C (HIV-1-C) is predominant in Southern Africa and preferably uses CCR5 co-receptor. Therefore, a significant proportion of HIV-1-C CXCR4 utilizing viruses (X4) may compromise the effectiveness of Maraviroc. This analysis examined coreceptor preferences in early and chronic HIV-1-C infections across Africa. African HIV-1-C Envelope gp120 V3-loop sequences sampled from 1988 to 2014 were retrieved from Los Alamos HIV Sequence Database. Sequences from early infections (< 186 days post infection) and chronic infections (> 186 days post infection) were analysed for predicted co-receptor preferences using Geno2Pheno [Coreceptor] 10% FPR, Phenoseq-C, and PSSMsinsi web tools. V3-loop diversity was determined, and viral subtype was confirmed by phylogenetic analysis. National treatment guidelines across Africa were reviewed for Maraviroc recommendation. Sequences from early (n = 6316) and chronic (n = 7338) HIV-1-C infected individuals from 10 and 15 African countries respectively were available for analyses. Overall, 518/6316 (8.2%; 95% CI 0.7–9.3) of early sequences were X4, with Ethiopia and Malawi having more than 10% each. For chronic infections, 8.3% (95% CI 2.4–16.2) sequences were X4 viruses, with Ethiopia, Tanzania, and Zimbabwe having more than 10% each. For sequences from early chronic infections (< 1 year post infection), the prevalence of X4 viruses was 8.5% (95% CI 2.6–11.2). In late chronic infections (≥ 5 years post infection), X4 viruses were observed in 36% (95% CI − 16.3 to 49.9), with two countries having relatively high X4 viruses: South Africa (43%) and Malawi (24%). The V3-loop amino acid sequence were more variable in X4 viruses in chronic infections compared to acute infections, with South Africa, Ethiopia and Zimbabwe showing the highest levels of V3-loop diversity. All sequences were phylogenetically confirmed as HIV-1-C and clustered according to their co-receptor tropism. In Africa, Maraviroc is registered only in South Africa and Uganda. Our analyses illustrate that X4 viruses are present in significantly similar proportions in early and early chronic HIV-1 subtype C infected individuals across Africa. In contrast, in late chronic infections, X4 viruses increase 3–5 folds. We can draw two inferences from our observations: (1) to enhance the utility of Maraviroc in chronic HIV subtype C infections in Africa, prior virus co-receptor determination is needed; (2) on the flip side, research on the efficacy of CXCR4 antagonists for HIV-1-C infections is encouraged. Currently, the use of Maraviroc is very limited in Africa.
Detection of HIV-1 RNA/DNA and CD4 mRNA in feces and urine from chronic HIV-1 infected subjects with and without anti-retroviral therapy
Springer Science and Business Media LLC - Tập 6 Số 1 - 2009
Ayan K. Chakrabarti, Lori Caruso, Ming Ding, Chengli Shen, William Buchanan, Phalguni Gupta, Charles R. Rinaldo, Yue Chen
Abstract

HIV-1 infects gut associated lymphoid tissues (GALT) very early after transmission by multiple routes. The infected GALT consequently serves as the major reservoir for HIV-1 infection and could constantly shed HIV-1 and CD4+T cells into the intestinal lumen. To examine this hypothesis, we monitored HIV-1 RNA/DNA and CD4 mRNA in fecal samples of chronically infected subjects with and without antiretroviral therapy (ART). We compared this to levels of HIV-1 RNA/DNA in urine and blood from the same subjects. Our results show that HIV-1 DNA, RNA and CD4 mRNA were detected in 8%, 19% and 31% respectively, of feces samples from infected subjects with detectable plasma viral load, and were not detected in any of subjects on ART with undetectable plasma viral load. In urine samples, HIV-1 DNA was detected in 24% of infected subjects with detectable plasma viral load and 23% of subjects on ART with undetectable plasma viral load. Phylogenetic analysis of the envelope sequences of HIV-1 revealed distinct virus populations in concurrently collected serum, feces and urine samples from one subject. In addition, our study demonstrated for the first time the presence of CD4 mRNA in fecal specimens of HIV-1 infected subjects, which could be used to assess GALT pathogenesis in HIV-1 infection.

The adult prevalence of HIV in Zambia: results from a population based mobile testing survey conducted in 2013–2014
Springer Science and Business Media LLC - Tập 13 - Trang 1-9 - 2016
Pascalina Chanda-Kapata, Nathan Kapata, Eveline Klinkenberg, Ngosa William, Liwewe Mazyanga, Katoba Musukwa, Elizabeth Chizema Kawesha, Felix Masiye, Peter Mwaba
To estimate the adult prevalence of HIV among the adult population in Zambia and determine whether demographic characteristics were associated with being HIV positive. A cross sectional population based survey to asses HIV status among participants aged 15 years and above in a national tuberculosis prevalence survey. Counselling was offered to participants who tested for HIV. The prevalence was estimated using a logistic regression model. Univariate and multivariate associations of social demographic characteristics with HIV were determined. Of the 46,099 individuals who were eligible to participate in the survey, 44,761 (97.1 %) underwent pre-test counselling for HIV; out of which 30,605 (68.4 %) consented to be tested and 30, 584 (99.9 %) were tested. HIV prevalence was estimated to be 6.6 % (95 % CI 5.8–7.4); with females having a higher prevalence than males 7.7 % (95 % CI 6.8–8.7) versus 5.2 % (95 % CI 4.4–5.9). HIV prevalence was higher among urban (9.8 %; 95 % CI 8.8–10.7) than rural residents (5.0 %; 95 % CI 4.3–5.8). The risk of HIV was double among urban dwellers than among their rural counterparts. Being divorced or widowed was associated with a threefold higher risk of being HIV positive than being never married. The risk of being HIV positive was four times higher among those with tuberculosis than those without tuberculosis. HIV prevalence was lower than previously estimated in the country. The burden of HIV showed sociodemographic disparities signifying a need to target key populations or epidemic drivers. Mobile testing for HIV on a national scale in the context of TB prevalence surveys could be explored further in other settings.
A structural equation modeling approach to investigate HIV testing willingness for men who have sex with men in China
Springer Science and Business Media LLC - Tập 20 - Trang 1-5 - 2023
Han Jiang, Wei He, Haiying Pan, Xiaoni Zhong
A substantial risk of contracting Human immunodeficiency virus (HIV) exists among men who have sex with men (MSM), and HIV infection rates have been rising. This study aimed to analyze the factors influencing the Chinese MSM population’s intention to test for HIV. Nonprobability sampling techniques were employed in June 2022 to recruit MSM in Chongqing and Sichuan, China. The data were analyzed using structural equation modeling (SEM), which is based on the knowledge-attitude-behavior (KAB) theory. Among 1687 participants, 964 (57.1%) of the MSM were willing to have an HIV test. The results of the structural equation modeling (SEM) showed that knowledge, attitude, and behavior all influenced the testing intention, with attitude having the greatest impact (total effect of 0.22). HIV testing needs to be increased among MSM as they exhibit a moderate willingness to test. Improving education on HIV knowledge and risk behavior might enhance the willingness of MSM to test for HIV in China.
The role of the glycosyl moiety of myricetin derivatives in anti-HIV-1 activity in vitro
Springer Science and Business Media LLC - Tập 14 Số 1 - 2017
Joseph T. Ortega, Alírica I. Suárez, María Luisa Serrano, Jani Baptista, Flor H. Pujol, Héctor R. Rangel
Use of taste-masking product, FLAVORx, to assist Thai children to ingest generic antiretrovirals
Springer Science and Business Media LLC - Tập 3 - Trang 1-5 - 2006
Torsak Bunupuradah, Siripan Wannachai, Arpa Chuamchaitrakool, Jintana Intasan, Thantip Nuchapong, Woodie Neiss, Kenny Kramm, Chitsanu Pancharoen, David Burger, Jintanat Ananworanich
We evaluated whether FLAVORx helped thirty Thai children take opened capsule, crushed tablets and liquid generic ARVs with more ease. All children had excellent adherence, evaluated by PACTG Standard International Questionnaire and interviewing, before and after one month of FLAVORx. Eighty percent took ARV with more ease and wish to continue FLAVORx. Strawberry was the most popular flavor.
Uptake of retroviral pre-exposure prophylaxis and its associated factors among female sex workers, Northwest Ethiopia
Springer Science and Business Media LLC - Tập 20 - Trang 1-5 - 2023
Belayneh Fentahun Shibesh, Aragaw Bitew Admas, Amarech Wondie Lake, Samuel Befekadu Getu, Daniel Tarekegn Worede
Pre-exposure prophylaxis is the use of antiretroviral medications by HIV-negative individuals to prevent infection before exposure. Ethiopia has made progress in reducing new HIV infections, but the burden remains high with ongoing challenges in prevention uptake. This study examined the utilization and factors associated with pre-exposure prophylaxis among female sex workers. A community-based cross-sectional study design was conducted in Bahir Dar city administration among female sexual workers in 2022. The results were collected using a pre-tested and structured questionnaire. Epi data for data entry and social package for social science for analysis were used. Overall, 15.9% (CI: 12.0-21.1) of female sexual workers received pre-exposure prophylaxis. Parents’ living condition (only father alive [AOR = 0.23, 95% CI, 0.02–0.64], only mother alive [AOR = 0.31, 95% CI, 0.02–0.74]), marital status being single (AOR = 0.27, 95% CI, 0.06–0.94), having history of STI (AOR = 2.82, 95% CI, 1.60–4.77) were associated with pre-exposure prophylaxis uptake. This study showed low pre-exposure prophylaxis uptake. The study identified a history of sexually transmitted infections, marital status, and parent living conditions as significant factors. To increase pre-exposure prophylaxis uptake and reduce HIV incidence, an awareness campaign, tailored support, targeted interventions, and addressing concerns of high-risk groups are needed.
Antiretroviral activity of the aminothiol WR1065 against Human Immunodeficiency virus (HIV-1) in vitro and Simian Immunodeficiency virus (SIV) ex vivo
Springer Science and Business Media LLC - Tập 6 - Trang 1-10 - 2009
Miriam C Poirier, Ofelia A Olivero, Andrew W Hardy, Genoveffa Franchini, Jennifer P Borojerdi, Vernon E Walker, Dale M Walker, Gene M Shearer
WR1065 is the free-thiol metabolite of the cytoprotective aminothiol amifostine, which is used clinically at very high doses to protect patients against toxicity induced by radiation and chemotherapy. In an earlier study we briefly reported that the aminothiol WR1065 also inhibits HIV-1 replication in phytohemagglutinin (PHA)-stimulated human T-cell blasts (TCBs) infected in culture for 2 hr before WR1065 exposure. In this study we expanded the original observations to define the dose-response curve for that inhibition, and address the question of additive effects for the combination of WR1065 plus Zidovudine (AZT). Here we also explored the effect of WR1065 on SIV by examining TCBs taken from macaques with well-established infections several months with SIV. TCBs from healthy human donors were infected for 2 hr with HIV-1, and viral replication (p24) was measured after 72 hr of incubation with or without WR1065, AZT, or both drugs. HIV-1 replication, in HIV-1-infected human TCBs, was inhibited by 50% at 13 μM WR1065, a dose at which 80% of the cells were viable. Cell cycle parameters were the same or equivalent at 0, 9.5 and 18.7 μM WR1065, showing no drug-related toxicity. Combination of AZT with WR1065 showed that AZT retained antiretroviral potency in the presence of WR1065. Cultured CD8+ T cell-depleted PHA-stimulated TCBs from Macaca mulatta monkeys chronically infected with SIV were incubated 17 days with WR1065, and viral replication (p27) and cell viability were determined. Complete inhibition (100%) of SIV replication (p27) was observed when TCBs from 3 monkeys were incubated for 17 days with 18.7 μM WR1065. A lower dose, 9.5 μM WR1065, completely inhibited SIV replication in 2 of the 3 monkeys, but cells from the third macaque, with the highest viral titer, only responded at the high WR1065 dose. The study demonstrates that WR1065 and the parent drug amifostine, the FDA-approved drug Ethyol, have antiretroviral activity. WR1065 was active against both an acute infection of HIV-1 and a chronic infection of SIV. The data suggest that the non-toxic drug amifostine may be a useful antiretroviral agent given either alone or in combination with other drugs as adjuvant therapy.
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