Genetic diversity and drug resistance of HIV-1 among infected pregnant women newly diagnosed in Luanda, Angola.
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ABSTRACT:
SUBMITTER: Sebastiao CS
PROVIDER: S-EPMC6879122 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The increase in HIV infection and drug-resistant strains is an important public health concern, especially in resource-limited settings. However, the identification of factors related to the propagation of infectious diseases represents a crucial target offering an opportunity to reduce health care costs as well as deepening the focus on preventing infection in high-risk groups. In this study, we investigate the factors related to drug resistance among HIV-infected pregnant women in Luanda, the capital city of Angola. This was a part of a cross-sectional study conducted with 42 HIV-positive pregnant women. A blood sample was collected, and HIV-1 genotyping was carried out using an in-house method. Multivariate analyses were performed to determine the interaction between sociodemographic characteristics and drug resistance. HIV drug resistance was detected in 44.1% of the studied population. High probabilities of drug resistance were observed for HIV-infected pregnant women living in rural areas (AOR: 2.73; 95% CI: 0.50-14.9) with high educational level (AOR: 6.27; 95% CI: 0.77-51.2) and comorbidities (AOR: 5.47; 95% CI: 0.28-106) and infected with a HIV-1 non-B subtype other than subtype C (AOR: 1.60; 95% CI: 0.25-10.3). The present study reports high HIV drug resistance. Furthermore, older-age, rural areas, high educational levels, unemployed status, having comorbidities, and HIV-1 subtypes were factors related to drug resistance. These factors impact on drug susceptibility and need to be urgently addressed in order to promote health education campaigns able to prevent the spread of drug-resistant HIV strains in Angola.
| S-EPMC8005960 | biostudies-literature
Project description:BackgroundGenetic variability and liability to develop drug-resistant mutations are the main characteristics of HIV-1, which can not only increase the risk of antiretroviral treatment (ART) failure, but also can lead to the spread of resistant strains. We aim to investigate the distribution of HIV-1 genotypes and prevalence of pretreatment drug resistance (PDR) in ART-naïve HIV-1 infected patients in Shanghai China.MethodsA cross-sectional study was performed among the newly diagnosed ART-naive HIV-1 infected patients during the period from January 2017 to November 2017 in Shanghai Public Health Clinical Center. The target fragment of 1316 bp in the pol gene spanning the reverse transcriptase and protease regions was amplified using a nested polymerase chain reaction. HIV-1 genotypes were determined by phylogenetic analysis, and PDR associated mutations were determined according to Stanford University HIV Drug Resistance Database ( http://hivdb.stanford.edu/ ).ResultsWe successfully amplified pol gene sequences from blood samples of 317 patients, of whom 95.3% were male, and 68.8% were men who have sex with men. The median age was 33 years; and the median CD4 count was 275 cells/μL. The predominant HIV-1 genotype was circulating recombinant form (CRF) 01_AE (53.0%, 168/317), followed by CRF07_BC (29.7%, 94/317), B (7.6%, 24/317), CRF08_BC (1.9%, 6/317), CRF55_01B (1.9%, 6/317), CRF 59_01B (0.9%, 3/317). In addition, 5% (16/317) HIV-1 strains were identified as other subtypes or CRFs/URFs (unique recombinant forms). The overall prevalence of PDR was 17.4% (55/317). PDR frequency to non-nucleoside reverse transcriptase inhibitor (NNRTI, 16.4%) was much higher than that to nucleoside reverse transcriptase inhibitor (NRTI, 4.7%) and protease inhibitor (PI, 0.6%). The most common HIV-1 mutation pattern for NNRTI and NRTI were V179D/E (10.1%, 32/317) and M184 V (2.8%, 9/317), respectively. About half (49.1%, 27/55) of the HIV-1 strains with mutation presented as potential low-level resistant to NNRTI attributed to V179D/E.ConclusionThe distribution of HIV-1 genotypes in Shanghai China is diverse and complex. The high prevalence of PDR highlights the significance of baseline HIV-1 drug resistance testing. Non-NNRTI-containing regimen may be the preferred initial therapy for newly diagnosed HIV-1 patients in Shanghai in the absence of PDR test results.
| S-EPMC6454613 | biostudies-literature
Project description:BackgroundHIV and HBV infections remain responsible for high rate of morbidity and mortality in many African Countries, affecting women and newborns. This study aims to analyze the spatial pattern of HIV and HBV infections in pregnant women in Luanda, Angola, and the statistical association between HIV and HBV and socio-economic characteristics, hygiene, and health status.MethodsDetection of anti-HIV antibodies (total anti-HIV-1, anti-HIV-2 and HIV-1 p24 antigen) and Hepatitis B antigens (HBsAg, HBeAg) and antibodies (anti-HBc Total II, HBc IgM, Anti-HBsT II) was performed by Enzyme Linked Fluorescent Assay (ELFA) in serum samples of 878 pregnant women attended at the Lucrecia Paim Maternity Hospital (LPMH). Data were collected by questionnaire after written consent, and spatial distribution was assessed through a Kernel Density Function. The potential risk factors associated with HIV HBV infection were evaluated using bivariate and multivariate binomial logistic regression analysis.ResultsAnti-HIV antibodies were positive in 118 samples (13.4%) and HBV infection were positive in 226 (25.7%). The seroprevalence of HIV/HBV coinfection was of 6.3%. The results showed that the seroprevalence of HBV was similar in most municipalities: 25.8% in Belas; 26.6% in Viana; 27.6% in Luanda; 19.2% in Cacuaco; and 15.6% Cazenga. For HIV, the seroprevalence was also close ranges among the municipalities: 10.0% in Belas; 14.5% in Viana 14.9% in Luanda and 12.5% in Cazenga. However, the seroprevalence in municipality of in Cacuaco was lower (5.8%) and bivariate and multivariate analysis showed a lower risk for HIV in this area (OR 0.348, CI 0.083-0.986; OR 0.359, CI 0.085-1.021). The multivariate analysis had also showed a significant increased risk for HIV in women with 2 or 3 births (OR 1.860, CI 1.054-3.372).ConclusionsOur results underlined the need to improve the screening and clinical follow-up of HIV and HBV in Angola, as well the educational campaigns to prevent not only the morbidity and mortality associated with these diseases, but also their transmission, mainly in women in reproductive age and pregnant, encouraging the pre-natal consultations in order to avoid mother-to-child transmission.
| S-EPMC8642931 | biostudies-literature
Project description:We report a study on toxoplasmosis in pregnant women in Luanda, Angola, determining the seroprevalence, geospatial distribution and its association with socio-economic features, dietary habits and hygiene and health conditions. Anti-Toxoplasma gondii IgG and IgM were quantified in serum samples of women attended at the Lucrecia Paim Maternity Hospital between May 2016 and August 2017. The IgG avidity test and qPCR assay were used for dating the primary infection. Data were collected by questionnaire after written consent, and spatial distribution was assessed through a Kernel Density Function. The potential risk factors associated with Toxoplasma infection were evaluated using bivariate and multivariate binomial logistic regression analysis. Anti-T. gondii antibodies were quantified in 878 pregnant women, and 346 (39.4%) samples were IgG positive, 2 (0.2%) positive for IgM and IgG, and 530 (60.4%) negative for both immunoglobulins. The longitudinal study showed that none of the seronegative women seroconverted during the survey. Regarding other infections, 226 (25.7%) were positive for hepatitis B, while 118 (13.4%) were HIV-positive. The seroprevalence of toxoplasmosis was similar in most municipalities: 43.8% in Cazenga (28 of 64); 42.5% in Viana (88 of 207); 42.3% in Cacuaco (22 of 52); and 41.1% in Luanda ((179 of 435). In contrast, the seroprevalence in municipality of Belas was lower (25.8%; 31 of 120) and bivariate and multivariate analysis has shown a lower risk for toxoplasmosis in this area (OR 0.479, CI: 0.305-0.737; OR 0.471, CI: 0.299-0.728). The multivariate analysis has shown a significant increased risk for toxoplasmosis in women in the last trimester of pregnancy (OR 1.457, CI: 1.011-2.102), suffering spontaneous abortion (OR 1.863, CI: 1.014-3.465) and having pets at home (OR 1.658, CI: 1.212-2.269). Also, women who tested positive for hepatitis B (OR 1.375, CI: 1.008-1.874) and HIV (OR 1.833, CI: 1.233-2.730) had a significant increased risk for T. gondii infection. In conclusion, our study showed that a large number of pregnant women are not immunized for toxoplasmosis and identified the risk factors for this infection in Luanda. It is crucial to establish the diagnosis of primary maternal infection as well as the diagnosis of congenital toxoplasmosis. Our results underlined the need for diagnostic and clinical follow-up of toxoplasmosis, HIV and hepatitis B during pregnancy.
| S-EPMC7647088 | biostudies-literature
Project description:BackgroundThe study goal was to describe etravirine pharmacokinetics during pregnancy and postpartum in HIV-infected women.MethodsIMPAACT P1026s and PANNA are on-going, non-randomized, open-label, parallel-group, multi-center phase-IV prospective studies in HIV-infected pregnant women. Intensive steady-state 12-h pharmacokinetic profiles were performed from 2nd trimester through postpartum. Etravirine was measured at two labs using validated ultra performance liquid chromatography (detection limits: 0.020 and 0.026 mcg/mL).ResultsFifteen women took etravirine 200 mg twice-daily. Etravirine AUC0-12 was higher in the 3rd trimester compared to paired postpartum data by 34% (median 8.3 vs. 5.3 mcg*h/mL, p = 0.068). Etravirine apparent oral clearance was significantly lower in the 3rd trimester of pregnancy compared to paired postpartum data by 52% (median 24 vs. 38 L/h, p = 0.025). The median ratio of cord blood to maternal plasma concentration at delivery was 0.52 (range: 0.19-4.25) and no perinatal transmission occurred.ConclusionEtravirine apparent oral clearance is reduced and exposure increased during the third trimester of pregnancy. Based on prior dose-ranging and safety data, no dose adjustment is necessary for maternal health but the effects of etravirine in utero are unknown. Maternal health and infant outcomes should be closely monitored until further infant safety data are available.Clinical trial registrationThe IMPAACT protocol P1026s and PANNA study are registered at ClinicalTrials.gov under NCT00042289 and NCT00825929.
| S-EPMC4972814 | biostudies-literature
Project description:ObjectivesTo assess HIV-1 diversity, transmission dynamics and prevalence of transmitted drug resistance (TDR) in Angola, five years after ART scale-up.MethodsPopulation sequencing of the pol gene was performed on 139 plasma samples collected in 2009 from drug-naive HIV-1 infected individuals living in Luanda. HIV-1 subtypes were determined using phylogenetic analysis. Drug resistance mutations were identified using the Calibrated Population Resistance Tool (CPR). Transmission networks were determined using phylogenetic analysis of all Angolan sequences present in the databases. Evolutionary trends were determined by comparison with a similar survey performed in 2001.Results47.1% of the viruses were pure subtypes (all except B), 47.1% were recombinants and 5.8% were untypable. The prevalence of subtype A decreased significantly from 2001 to 2009 (40.0% to 10.8%, P = 0.0019) while the prevalence of unique recombinant forms (URFs) increased > 2-fold (40.0% to 83.1%, P < 0.0001). The most frequent URFs comprised untypable sequences with subtypes H (U/H, n = 7, 10.8%), A (U/A, n = 6, 9.2%) and G (G/U, n = 4, 6.2%). Newly identified U/H recombinants formed a highly supported monophyletic cluster suggesting a local and common origin. TDR mutation K103N was found in one (0.7%) patient (1.6% in 2001). Out of the 364 sequences sampled for transmission network analysis, 130 (35.7%) were part of a transmission network. Forty eight transmission clusters were identified; the majority (56.3%) comprised sequences sampled in 2008-2010 in Luanda which is consistent with a locally fuelled epidemic. Very low genetic distance was found in 27 transmission pairs sampled in the same year, suggesting recent transmission events.ConclusionsTransmission of drug resistant strains was still negligible in Luanda in 2009, five years after the scale-up of ART. The dominance of small and recent transmission clusters and the emergence of new URFs are consistent with a rising HIV-1 epidemics mainly driven by heterosexual transmission.
| S-EPMC4257534 | biostudies-literature
Project description:Free-roaming dogs and cats represent potential reservoirs for zoonotic vector-borne pathogens shedding to the human population. Given the health impact of these pathogens, we searched free-roaming dogs and cats included in an animal population control program from Luanda, Angola, for Bartonella and hemotropic mycoplasma infection. We report the detection of Bartonella henselae (2/66; 3%), Candidatus Mycoplasma haemominutum (5/66; 7.5%) and Mycoplasma haemofelis (1/66; 1.5%) in cats. One dog was found positive for Mycoplasma haemocanis (1/20; 5%). This is the first report of Bartonella henselae infections in stray cats and of hemotropic mycoplasmas in cats and dogs from Angola. Despite the relatively small sample size, our results sustain the hypothesis of uncontrolled circulation of these agents in highly mobile synanthropic animal populations of Luanda. Population and vector control could contribute to reducing the likelihood for animal-to-animal and animal-to-human transmission.
| S-EPMC8230469 | biostudies-literature
Project description:BACKGROUND:Rilpivirine pharmacokinetics is defined by its absorption, distribution, metabolism, and excretion. Pregnancy can affect these factors by changes in cardiac output, protein binding, volume of distribution, and cytochrome P450 (CYP) 3A4 activity. Rilpivirine is metabolized by CYP3A4. The impact of pregnancy on rilpivirine pharmacokinetics is largely unknown. METHODS:International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is a multicenter, nonblinded, prospective study evaluating antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving rilpivirine 25 mg once daily as part of their combination antiretrovirals for clinical care. Thirty-two women were enrolled in this study. Intensive pharmacokinetic sampling was performed at steady state during the second trimester, the third trimester, and postpartum. Maternal and umbilical cord blood samples were obtained at delivery. Plasma rilpivirine concentration was measured using liquid chromatography-mass spectrometry; lower limit of quantitation was 10 ng/mL. RESULTS:Median (range) AUC0-24 were 1969 (867-4987, n = 15), 1669 (556-4312, n = 28), and 2387 (188-6736, n = 28) ng·h/mL in the second trimester, the third trimester, and postpartum, respectively (P < 0.05 for either trimester vs postpartum). Median (range) C24 were 63 (37-225, n = 17), 56 (<10-181, n = 30), and 81 (<10-299, n = 28) ng/mL (P < 0.05 for either trimester vs postpartum). High variability in pharmacokinetic parameters was observed between subjects. Median (range) cord blood/maternal concentration ratio was 0.55 (0.3-0.8, n = 21). Delivery HIV-1 RNA was ?50 copies per milliliter in 70% and ?400 copies per milliliter in 90% of women. Cmin were significantly lower at 15 visits with detectable HIV-1 RNA compared with 61 visits with undetectable HIV-1 RNA, 29 (<10-93) vs 63 (15-200) ng/mL (P = 0.0001). Cmin was below the protein binding-adjusted EC90 concentration (12.2 ng/mL) at 4 visits in 3 of 31 women (10%). CONCLUSIONS:Rilpivirine exposure is lower during pregnancy compared with postpartum and highly variable. Ninety percent of women had minimum concentrations above the protein binding-adjusted EC90 for rilpivirine.
| S-EPMC4911231 | biostudies-literature
Project description:ObjectiveTo describe the pharmacokinetics of maraviroc in human immunodeficiency virus (HIV)-infected women during pregnancy and post partum.MethodsHIV-infected pregnant women receiving maraviroc as part of clinical care had intensive steady-state 12-hour pharmacokinetic profiles performed during the third trimester and ≥2 weeks after delivery. Cord blood samples and matching maternal blood samples were taken at delivery. The data were collected in 2 studies: P1026 (United States) and PANNA (Europe). Pharmacokinetic parameters were calculated.ResultsEighteen women were included in the analysis. Most women (12; 67%) received 150 mg of maraviroc twice daily with a protease inhibitor, 2 (11%) received 300 mg twice daily without a protease inhibitor, and 4 (22%) had an alternative regimen. The geometric mean ratios for third-trimester versus postpartum maraviroc were 0.72 (90% confidence interval, .60-.88) for the area under the curve over a dosing interval (AUCtau) and 0.70 (0.58-0.85) for the maximum maraviroc concentration. Only 1 patient showed a trough concentration (Ctrough) below the suggested target of 50 ng/mL, both during pregnancy and post partum. The median ratio of maraviroc cord blood to maternal blood was 0.33 (range, 0.03-0.56). The viral load close to delivery was <50 copies/mL in 13 women (76%). All children were HIV negative at testing.ConclusionsOverall maraviroc exposure during pregnancy was decreased, with a reduction in AUCtau and maximum concentration of about 30%. Ctrough was reduced by 15% but exceeded the minimum Ctrough target concentration. Therefore, the standard adult dose seems sufficient in pregnancy.Clinical trials registrationNCT00825929 and NCT000422890.
| S-EPMC4614410 | biostudies-literature
Project description:BackgroundThe emergence of an HIV-1 epidemic in China was first recognized in Dehong, western Yunnan. Due to its geographic location, Dehong contributed greatly in bridging HIV-1 epidemics in Southeast Asia and China through drug trafficking and injection drug use; and also extensively to the HIV genetic diversity in Yunnan and China. We attempt to monitor HIV-1 in this area by studying the HIV-1 genetic distribution and transmitted drug resistance (TDR) in various at-risk populations.MethodsBlood samples from a total of 320 newly HIV-1 diagnosed individuals, who were antiretroviral therapy (ART)-naive, were collected from January 2009 to December 2010 in 2 counties in Dehong. HIV-1 subtypes and pol gene drug resistance (DR) mutations were genotyped.ResultsAmong 299 pol sequences successfully genotyped (93.4%), subtype C accounted for 43.1% (n=129), unique recombinant forms (URFs) for 18.4% (n=55), CRF01_AE for 17.7% (n=54), B for 10.7% (n=32), CRF08_BC for 8.4% (n=25) and CRF07_BC for 1.7% (n=5). Subtype distribution in patients infected by different transmission routes varied. In contract to the previous finding of CRF01_AE predominance in 2002-2006, subtype C predominated in both injecting drug users (IDUs) and heterosexually transmitted populations in this study. Furthermore, we found a high level of BC, CRF01_AE/C and CRF01_AE/B/C recombinants suggesting the presence of active viral recombination in the area. TDR associated mutations were identified in 4.3% (n=13) individuals. A total of 1.3% of DR were related to protease inhibitors (PIs), including I85IV, M46I and L90M; 0.3% to nucleoside reverse transcriptase inhibitors (NRTIs), including M184I; and 2.7% to non-nucleoside reverse transcriptase inhibitors (NNRTIs), including K103N/S, Y181C, K101E and G190A.ConclusionOur work revealed diverse HIV-1 subtype distributions and intersubtype recombinations. We also identified a low but significant TDR mutation rate among ART-naive patients. These findings enhance our understanding of HIV-1 evolution and are valuable for the development and implementation of a comprehensive public health approach to HIV-1 DR prevention and treatment in the region.
| S-EPMC3552723 | biostudies-literature