High prevalence of late presentation of ART-naive perinatally infected children for care in Pune, India.
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ABSTRACT:
SUBMITTER: Nimkar S
PROVIDER: S-EPMC7431379 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Abstract We report the presence of drug resistance mutations in 7.4% (2/27) of the treatment-naive, HIV-1-infected children in Pune, India, who had HIV-1 RNA levels >1,000 copies/ml. Nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations, namely A98G and K103N, were observed in two separate sequences. In addition, three study sequences displayed three separate HIV-1 protease minor resistance mutations-L10I, A71T, and T74S. These preliminary data from Pune, India, reporting the presence of HIVDR in treatment-naive, HIV-1-infected children, reinforces the need to conduct large-scale studies to assess the prevalence of primary HIVDR in the pediatric population, which in turn will aid in planning protocols and policies related to antiretroviral treatment for the pediatric population.
| S-EPMC3938931 | biostudies-literature
Project description:ObjectivesThe aim of this study was to assess the prevalence of HIV drug resistance (HIVDR) in HIV-infected ART-naive and -experienced patients in Sierra Leone.Patients and methodsWe conducted a cross-sectional study of HIV-positive adults aged ≥18 years at Connaught Hospital in Freetown, Sierra Leone in November 2017. Sequencing was performed in the reverse transcriptase, protease and integrase regions, and interpreted using the Stanford HIVDR database and WHO 2009 mutation list.ResultsTwo hundred and fifteen HIV-infected patients were included (64 ART naive and 151 ART experienced). The majority (66%) were female, the median age was 36 years and the median ART exposure was 48 months. The majority (83%) were infected with HIV-1 subtype CRF02_AG. In the ART-naive group, the pretreatment drug resistance (PDR) prevalence was 36.7% (14.2% to NRTIs and 22.4% to NNRTIs). The most prevalent PDR mutations were K103N (14.3%), M184V (8.2%) and Y181C (4.1%). In the ART-experienced group, 64.4% harboured resistance-associated mutations (RAMs) and the overall prevalence of RAMs to NRTIs and NNRTIs was 85.2% (52/61) and 96.7% (59/61), respectively. The most prevalent RAMs were K103N (40.7%), M184V (28.8%), D67N (15.3%) and T215I/F/Y (15.3%). Based on the genotypic susceptibility score estimates, 22.4% of ART-naive patients and 56% of ART-experienced patients were not susceptible to first-line ART used in Sierra Leone.ConclusionsA high prevalence of circulating NRTI- and NNRTI-resistant variants was observed in ART-naive and -experienced HIV-1-infected patients in Sierra Leone. This necessitates the implementation of HIVDR surveillance programmes to inform national ART guidelines for the treatment and monitoring of HIV-infected patients in Sierra Leone.
| S-EPMC6587425 | biostudies-literature
Project description:Introduction: Resistance to antiretroviral drugs can complicate the management of HIV-1 infection and impair control of its spread. The aim of the current study was to investigate the prevalence and transmission of HIV-1 drug resistance among 106 antiretroviral therapy (ART)-naïve patients diagnosed in Iceland (1996-2012). Methods: HIV-1 polymerase sequences were analysed using the Calibrated Population Resistance tool. Domestic spread of transmitted drug resistance (TDR) was investigated through maximum likelihood and Bayesian approaches. Results: Among ART-naïve patients, the prevalence of TDR to any of the following classes (NRTIs, NNRTIs and PIs) was 8.5% (95% CI: 4.5%- 15.4%): 6.6% to NRTIs, 0.9% to NNRTIs, and 1.9% to PIs. The most frequent NRTI mutation detected was T215C/D (n=7, 5.7%). The only NNRTI mutation detected was K103N (n=1, 0.9%). PI mutations detected were M46I (n=1, 0.9%) and L90M (n=1, 0.9%). Six patients harbouring T215C/D, were linked in a supported phylogenetic cluster. No significant association was found between TDR and demographic or risk groups. Trend analysis showed a decrease in the prevalence of TDR (1996-2012, p=0.003). Conclusions: TDR prevalence in Iceland was at a moderate level and decreased during 1996-2012. Screening for TDR is recommended to limit its local spread and to optimize HIV-1 therapy. Abbreviations: ART: Anti-retroviral therapy; ARV: antiretroviral; ATV/r: atazanavir/ritonavir; AZT: azidothymidine; BEAST: Bayesian evolutionary analysis by sampling trees; CI: confidence interval; CPR: calibrated population resistance; CRF: circulating recombinant form; d4T: stavudine; EFV: efavirenz; FET: Fishers' exact test; FPV/r: fosamprenavir/ritonavir; HET: heterosexual; IDU: injection drug use; IDV/r: indinavir/ritonavir; LPV/r: lopinavir/ritonavir; MSM: men who have sex with men; M-W: Mann-Whitney U test; NFV: nelfinavir; NNRTIs: non-nucleoside reverse transcriptase inhibitors; NRTIs: nucleoside reverse transcriptase inhibitors; NVP: nevirapine; PIs: protease inhibitors; pol: polymerase gene; SDRM: surveillance drug resistance mutation; SQV/r: saquinavir/ritonavir; TDR: transmitted drug resistance.
| S-EPMC5475329 | biostudies-literature
Project description:BackgroundThe distribution of HPV genotypes, their association with rigorously confirmed cervical precancer endpoints, and factors associated with HPV infection have not been previously documented among HIV-infected women in India. We conducted an observational study to expand this evidence base in this population at high risk of cervical cancer.MethodsHIV-infected women (N = 278) in Pune, India underwent HPV genotyping by Linear Array assay. Cervical intraepithelial neoplasia (CIN) disease ascertainment was maximized by detailed assessment using cytology, colposcopy, and histopathology and a composite endpoint.ResultsCIN2+ was detected in 11.2% while CIN3 was present in 4.7% participants. HPV genotypes were present in 52.5% (146/278) and 'carcinogenic' HPV genotypes were present in 35.3% (98/278) HIV-infected women. 'Possibly carcinogenic' and 'non/unknown carcinogenic' HPV genotypes were present in 14.7% and 29.5% participants respectively. Multiple (? 2) HPV genotypes were present in half (50.7%) of women with HPV, while multiple 'carcinogenic' HPV genotypes were present in just over a quarter (27.8%) of women with 'carcinogenic' HPV. HPV16 was the commonest genotype, present in 12% overall, as well as in 47% and 50% in CIN2+ and CIN3 lesions with a single carcinogenic HPV infection, respectively. The carcinogenic HPV genotypes in declining order of prevalence overall included HPV 16, 56, 18, 39, 35, 51, 31, 59, 33, 58, 68, 45 and 52. Factors independently associated with 'carcinogenic' HPV type detection were reporting ? 2 lifetime sexual partners and having lower CD4+ count. HPV16 detection was associated with lower CD4+ cell counts and currently receiving combination antiretroviral therapy.ConclusionHPV16 was the most common HPV genotype, although a wide diversity and high multiplicity of HPV genotypes was observed. Type-specific attribution of carcinogenic HPV genotypes in CIN3 lesions in HIV-infected women, and etiologic significance of concurrently present non/unknown carcinogenic HPV genotypes await larger studies.
| S-EPMC3378535 | biostudies-literature
Project description:ObjectiveThe study was designed to assess the hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection scenario among the human immunodeficiency virus (HIV) infected patients attending a tertiary healthcare unit in eastern India. Additionally, clinical and virological characterization of these viruses, prior to antiretroviral therapy (ART) initiation was also done for better understanding of the disease profile.MethodsPool of ART-naive HIV/HBV co-infected and HIV mono-infected patients, participating in two different studies, were included in this study. HBV DNA was detected by nested-PCR amplification followed by HBV genotype determination and HBV reverse transcriptase (RT) region amplification and direct sequencing for detecting drug resistance.ResultsThe prevalence of HBsAg (11.3%) was higher compared to anti-HCV (1.9%) among the HIV infected ART-naive patients. Moreover, majority of the HBeAg positive HIV/HBV co-infected patients (87.7%) had HBV DNA ?20,000 IU/ml with median HBV DNA significantly higher than that of HBeAg negative subjects (5.7 log10 IU/ml vs. 4.2 log10 IU/ml; p<0.0001). Multivariate analysis also showed that HBeAg-positive status was independently associated with higher HBV DNA level (p?=?<0.001). Notably, 60.9% of the HBeAg negative co-infected subjects had HBV DNA ?2,000 IU/ml of which 37.0% had HBV DNA ?20,000 IU/ml. Genotype HBV/D (68.2%) was the predominant genotype followed by HBV/A (24.3%) and HBV/C (7.5%). Anti-HBV drug resistant mutations were detected in two (3.8%) of the ART-naive patients.ConclusionThe prevalence of HIV/HBV co-infection was relatively higher in our study subjects. HBeAg testing might provide clue for early treatment initiation. Furthermore, HBeAg negative patients are also associated with high HBV DNA levels and therefore require appropriate medical attention. Pre-treatment screening for anti-HBV drug resistant mutations is not necessary before ART initiation.
| S-EPMC3758335 | biostudies-literature
Project description:ObjectivesLong-term complications of HIV including low bone mineral density remain a concern. We studied the prevalence and predictors of low bone mineral density among South African perinatally HIV-infected adolescents (PHIVA) on antiretroviral therapy (ART).DesignCross-sectional analysis.MethodsBone health was evaluated by measuring the calcaneus stiffness index among PHIVA on ART. Low stiffness index was defined as z-score less than -2 SD compared with age-matched and sex-matched HIV-uninfected adolescents (HIV-).ResultOverall, 407 PHIVA (median age: 14 years; 50.4% female; median age at ART initiation: 4.2 years) and 92 HIV- (median age: 13.7 years; 54.4% female) were included. Median duration on ART was 9.8 years (interquartile range 6.8-11.5) with 38% initiating ART at 2 years or less of age. Stiffness index was lower in PHIVA (-0.19 vs. 0.43, P ≤ 0.001), respectively. During puberty, mean stiffness index increased with Tanner Stage in both PHIVA and HIV- but these increases were larger among HIV-; Tanner Stage II-III (96 vs. 101, P = 0.009) and Tanner Stage IV-V (104 vs. 112, P = 0.001). Among PHIVA, 52 (13%) had low stiffness index. After adjusting for age, sex and Tanner Stage, use of lopinavir/ritonavir [odds ratio (OR) = 2.31, P = 0.012] and viral load more than 50 copies/ml (OR = 2.06, P = 0.023) were associated with increased risk of low stiffness index, while use of efavirenz (OR = 0.41, P = 0.009) was associated with decreased risk of low stiffness index.ConclusionStiffness index was a significantly lower in PHIVA than in HIV-, especially during puberty. Among PHIVA, detectable viral load and use of lopinavir/ritonavir were risk factors for low stiffness index. Further longitudinal studies are important to determine the clinical implications.
| S-EPMC7606491 | biostudies-literature
Project description:A survey for estimation of goitre in school children in the Rural Health Training Centre, Shirur area was undertaken. A total of 4664 students from 17 schools were surveyed. The goitre prevalence was found to be 59.8% with visible goitre rate of 6.2% in pre- and peri-adolescent (10-19 years) age group. Thus a highly endemic goitre focus was located in Shirur, area in Pune District (Maharashtra). This area is located on the eastern tail-end slopes of Sahyadri Hills in Balaghat ranges, situated at an altitude of 533 metres. The area is generally drought prone and receives scanty rain, with poor agricultural practices. Environmental deficiency of iodine was found to be the main cause for this high prevalence of goitre.
| S-EPMC5529797 | biostudies-other
Project description:CONTEXT:Research shows, conclusively, that perinatal HIV infection has negative effects on cognitive functioning of children and adolescents. However, the extent of these cognitive impairments is unknown. Current literature does not document specific cognitive domains most affected in HIV-infected children and adolescents. OBJECTIVE:To systematically review and meta-analyze the degree of cognitive impairment, and the specific cognitive domains affected, in children and adolescents with perinatally acquired HIV infection. DATA SOURCES:We systematically searched 5 electronic bibliographic databases, namely: PubMed, PsychINFO, Academic Search Premier, Scopus, and WorldCat, by using a search protocol specifically designed for this study. STUDY SELECTION:Studies were selected on the basis of set a priori eligibility criteria. Titles, abstracts, and full texts were assessed by 2 independent reviewers. DATA EXTRACTION:Data from included studies were extracted into Microsoft Excel by 2 independent reviewers. RESULTS:Twenty-two studies were identified for inclusion in the systematic review and of this, 6 studies were included in the meta-analysis. Results from the meta-analysis indicated that working memory and executive function were the domains most affected by the HIV virus. LIMITATIONS:Only 27% of the included studies were suitable to enter into the meta-analysis. There was significant geographic bias in published studies, with only 32% (7/22) of included studies from sub-Saharan Africa. CONCLUSIONS:The evidence supports an association between HIV infection in children and adolescents and cognitive impairment in the domains of working memory, executive function and processing speed, with effect size estimates also providing some support for deficits in visual memory and visual-spatial ability.
| S-EPMC5079077 | biostudies-literature
Project description:The use of combination antiretroviral therapy (cART) comprising three antiretroviral medications from at least two classes of drugs is the current standard treatment for HIV infection in adults and children. Current World Health Organization (WHO) guidelines for antiretroviral therapy recommend early treatment regardless of immunologic thresholds or the clinical condition for all infants (less than one years of age) and children under the age of two years. For children aged two to five years current WHO guidelines recommend (based on low quality evidence) that clinical and immunological thresholds be used to identify those who need to start cART (advanced clinical stage or CD4 counts ? 750 cells/mm(3) or per cent CD4 ? 25%). This Cochrane review will inform the current available evidence regarding the optimal time for treatment initiation in children aged two to five years with the goal of informing the revision of WHO 2013 recommendations on when to initiate cART in children.To assess the evidence for the optimal time to initiate cART in treatment-naive, HIV-infected children aged 2 to 5 years.We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the AEGIS conference database, specific relevant conferences, www.clinicaltrials.gov, the World Health Organization International Clinical Trials Registry platform and reference lists of articles. The date of the most recent search was 30 September 2012.Randomised controlled trials (RCTs) that compared immediate with deferred initiation of cART, and prospective cohort studies which followed children from enrolment to start of cART and on cART.Two review authors considered studies for inclusion in the review, assessed the risk of bias, and extracted data on the primary outcome of death from all causes and several secondary outcomes, including incidence of CDC category C and B clinical events and per cent CD4 cells (CD4%) at study end. For RCTs we calculated relative risks (RR) or mean differences with 95% confidence intervals (95% CI). For cohort data, we extracted relative risks with 95% CI from adjusted analyses. We combined results from RCTs using a random effects model and examined statistical heterogeneity.Two RCTs in HIV-positive children aged 1 to 12 years were identified. One trial was the pilot study for the larger second trial and both compared initiation of cART regardless of clinical-immunological conditions with deferred initiation until per cent CD4 dropped to <15%. The two trials were conducted in Thailand, and Thailand and Cambodia, respectively. Unpublished analyses of the 122 children enrolled at ages 2 to 5 years were included in this review. There was one death in the immediate cART group and no deaths in the deferred group (RR 2.9; 95% CI 0.12 to 68.9). In the subgroup analysis of children aged 24 to 59 months, there was one CDC C event in each group (RR 0.96; 95% CI 0.06 to 14.87) and 8 and 11 CDC B events in the immediate and deferred groups respectively (RR 0.95; 95% CI 0.24 to 3.73). In this subgroup, the mean difference in CD4 per cent at study end was 5.9% (95% CI 2.7 to 9.1). One cohort study from South Africa, which compared the effect of delaying cART for up to 60 days in 573 HIV-positive children starting tuberculosis treatment (median age 3.5 years), was also included. The adjusted hazard ratios for the effect on mortality of delaying ART for more than 60 days was 1.32 (95% CI 0.55 to 3.16).This systematic review shows that there is insufficient evidence from clinical trials in support of either early or CD4-guided initiation of ART in HIV-infected children aged 2 to 5 years. Programmatic issues such as the retention in care of children in ART programmes in resource-limited settings will need to be considered when formulating WHO 2013 recommendations.
| S-EPMC3950819 | biostudies-literature
Project description:As the immune system develops with age, children combat infections better. HIV-1, however, targets an activated immune system, potentially rendering children increasingly permissive to HIV-1 infection as they grow. How HIV-1 fitness changes with age in children is unknown. Here, we estimated the within-host basic reproductive ratio, R0, a marker of viral fitness, in HIV-1 subtype C-infected children in India, aged between 84 days and 17 years. We measured serial viral load and CD4 T cell counts in 171 children who initiated first-line ART. For 25 children, regular and frequent measurements provided adequate data points for analysis using a mathematical model of viral dynamics to estimate R0. For the rest, we used CD4 counts for approximate estimation of R0. The viral load decline during therapy was biphasic. The mean lifespans of productively and long-lived infected cells were 1.4 and 27.8 days, respectively. The mean R0 was 1.5 in children aged < 5 years, increased with age, and approached 6.0 at 18 years, close to 5.8 estimated previously for adults. The tolerogenic immune environment thus compromises HIV-1 fitness in young children. Early treatment initiation, when the R0 is small, will likely improve viral control, in addition to suppressing the latent reservoir.
| S-EPMC7862260 | biostudies-literature