scholarly journals Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4–8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011–12 and 2012–13

2019 ◽  
Vol 19 (S1) ◽  
Author(s):  
Gillian M. Hunt ◽  
Johanna Ledwaba ◽  
Anna Salimo ◽  
Monalisa Kalimashe ◽  
Thu-Ha Dinh ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Transcriptase Inhibitor ◽  
Hiv Drug Resistance ◽  
Nnrti Resistance ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Nationally Representative ◽  
Reverse Transcriptase Inhibitor ◽  
Cd4 Cell ◽  
Hiv 1

Abstract Background South Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT). The first study was conducted in 2010 (under the dual therapy PMTCT policy), the second from 2011 to 12 (PMTCT Option A policy) and the third from 2012 to 13 (PMTCT Option A policy). From 2010 to 2013, infant non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure increased from single dose to daily throughout breastfeeding; maternal nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI exposure increased with initiation of NNRTI-and NRTI- containing triple antiretroviral therapy (ART) earlier in gestation and at higher CD4 cell counts. Methods Three nationally representative surveys were conducted in 2010, 2011–12 and 2012–13. During the surveys, mothers with known, unknown, or no exposure to antiretrovirals for PMTCT and their infants were included, and MTCT was measured. For this paper, infant dried blood spots (iDBS) from HIV PCR positive infants aged 4–8 weeks, with consent for additional iDBS testing, were analysed for HIV drug resistance at the National Institute of Communicable Diseases (NICD), SA, using an in-house assay validated by the Centers for Disease Control and Prevention (CDC). Total viral nucleic acid was extracted from 2 spots and amplified by nested PCR to generate a ~ 1 kb amplicon that was sequenced using Sanger sequencing technologies. Sequence assembly and editing was performed using RECall v3. Results Overall, HIV-1 drug resistance was detected in 51% (95% Confidence interval (CI) [45–58%]) of HIV PCR positive infants, 37% (95% CI [28–47%]) in 2010, 64% (95% CI [53–74%]) in 2011 and 63% (95% CI [47–77%]) in 2012 (p < 0.0001), particularly to the NNRTI drug class. Pooled analyses across all three surveys demonstrated that infants whose mothers received ART showed the highest prevalence of resistance (74%); 26% (21/82) of HIV PCR positive infants with no or undocumented antiretroviral drug (ARV) exposure harboured NNRTI resistance. Conclusions These data demonstrate increasing NNRTI resistance amongst newly-diagnosed infants in a high HIV prevalence setting where maternal ART coverage increased across the years, starting earlier in gestation and at higher CD4 cell counts. This is worrying as lifelong maternal ART coverage for HIV positive pregnant and lactating women is increasing. Also of concern is that resistant virus was detected in HIV positive infants whose mothers were not exposed to ARVs, raising questions about circulating resistant virus. Numbers in this group were too small to assess trends over the three years.

scholarly journals Safety, tolerance, and efficacy of atevirdine in asymptomatic human immunodeficiency virus-infected individuals.

1996 ◽  
Vol 40 (11) ◽  
pp. 2664-2668 ◽  
Author(s):  
A M Been-Tiktak ◽  
I Williams ◽  
H M Vrehen ◽  
J Richens ◽  
D Aldam ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Transcriptase Inhibitor ◽  
Viral Loads ◽  
Nonnucleoside Reverse Transcriptase Inhibitor ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Immunodeficiency Virus ◽  
Reverse Transcriptase Inhibitor ◽  
Cd4 Cell ◽  
Hiv 1

Atevirdine is a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). In this study we investigated the effect of atevirdine in asymptomatic antiretroviral naive HIV-infected patients with CD4+ cell counts of between 200 and 750 cells per mm3. Patients were randomized to receive 600 mg of atevirdine (n = 15) or a placebo (n = 15) three times a day for 12 weeks. There was no statistically significant effect of atevirdine on viral loads (HIV p24 antigen and HIV-1 RNA levels by PCR) or CD4+ cell counts. The data do not support the use of atevirdine as a monotherapy in the treatment of HIV-infected patients.

The Frequency of Adjusted Renal Dosing of Tenofovir DF and Its Effects on Patient Outcomes

2012 ◽  
Vol 26 (4) ◽  
pp. 397-400 ◽  
Author(s):  
Jacob A. Langness ◽  
Jason T. Hindman ◽  
Steven C. Johnson ◽  
Jennifer J. Kiser
Keyword(s):  
Transcriptase Inhibitor ◽  
Cd4 Cells ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Immunodeficiency Virus ◽  
Tenofovir Df ◽  
Nucleotide Reverse Transcriptase Inhibitor ◽  
Reverse Transcriptase Inhibitor ◽  
Cd4 Cell ◽  
Hiv 1

Tenofovir disoproxil fumarate (TDF), a nucleotide reverse transcriptase inhibitor used in the treatment of human immunodeficiency virus (HIV) and hepatitis B, is renally eliminated and has been associated with renal toxicities. Dose adjustments are recommended for patients with creatinine clearance (CrCL) <50 mL/min. We retrospectively determined the frequency in which HIV clinic providers adjusted TDF doses in patients with CrCL <50 mL/min over a 2-year period and compared clinical outcomes in patients who had TDF dose adjustments based on CrCL <50 mL/min versus those who did not. Thirty-nine patients with CrCL <50 mL/min were identified. Dose-adjusted patients (N = 9) continued their TDF-based antiretroviral regimens for 21 months longer following the first CrCL < 50 mL/min ( P = .0193) and had gains in CD4 cell counts over 12 months ( P = .0009). There were no statistically significant differences in CrCL or percentage of patients with detectable HIV-1 RNA at 6 and 12 months following first CrCL <50 mL/min in those who did versus did not have a TDF dose adjustment. In summary, HIV providers often failed to dose-adjust TDF in patients with CrCL <50 mL/min, but dose-adjusted patients appeared to stay on their TDF-based regimens longer and have greater gains in CD4 cells. Larger, prospective studies are needed to validate these results.

scholarly journals HIV-1 Phenotypic Reverse Transcriptase Inhibitor Drug Resistance Test Interpretation Is Not Dependent on the Subtype of the Virus Backbone

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e34708 ◽  
Author(s):  
Michelle Bronze ◽  
Kim Steegen ◽  
Carole L. Wallis ◽  
Hans De Wolf ◽  
Maria A. Papathanasopoulos ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Resistance Test ◽  
Test Interpretation ◽  
Inhibitor Drug ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

Diversity of HIV-1 subtypes and transmitted drug-resistance mutations among minority HIV-1 variants in a Turkish cohort

2021 ◽  
Vol 19 ◽  
Author(s):  
Rabia Can Sarinoglu ◽  
Uluhan Sili ◽  
Ufuk Hasdemir ◽  
Burak Aksu ◽  
Guner Soyletir ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Treatment Naïve ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

Background: The World Health Organization (WHO) recommends the surveillance of transmitted drug resistance mutations (TDRMs) to ensure the effectiveness and sustainability of HIV treatment programs. Objective: Our aim was to determine the TDRMs and evaluate the distribution of HIV-1 subtypes using and compared next-generation sequencing (NGS) and Sanger-based sequencing (SBS) in a cohort of 44 antiretroviral treatment-naïve patients. Methods: All samples that were referred to the microbiology laboratory for HIV drug resistance analysis between December 2016 and February 2018 were included in the study. After exclusions, 44 treatment-naive adult patients with a viral load of >1000 copies/mL were analyzed. DNA sequencing for reverse transcriptase and protease regions was performed using both DeepChek ABL single round kit and Sanger-based ViroSeq HIV-1 Genotyping System. The mutations and HIV-1 subtypes were analyzed using the Stanford HIVdb version 8.6.1 Genotypic Resistance software, and TDRMs were assessed using the WHO surveillance drug-resistance mutation database. HIV-1 subtypes were confirmed by constructing a maximum-likelihood phylogenetic tree using Los Alamos IQ-Tree software. Results: NGS identified nucleos(t)ide reverse transcriptase inhibitor (NRTI)-TDRMs in 9.1% of the patients, non-nucleos(t)ide reverse transcriptase inhibitor (NNRTI)-TDRMs in 6.8% of the patients, and protease inhibitor (PI)-TDRMs in 18.2% of the patients at a detection threshold of ≥1%. Using SBS, 2.3% and 6.8% of the patients were found to have NRTI- and NNRTI-TDRMs, respectively, but no major PI mutations were detected. M41L, L74I, K65R, M184V, and M184I related to NRTI, K103N to NNRTI, and N83D, M46I, I84V, V82A, L24I, L90M, I54V to the PI sites were identified using NGS. Most mutations were found in low-abundance (frequency range: 1.0% - 4.7%) HIV-1 variants, except M41L and K103N. The subtypes of the isolates were found as follows; 61.4% subtype B, 18.2% subtype B/CRF02_AG recombinant, 13.6% subtype A, 4.5% CRF43_02G, and 2.3% CRF02_AG. All TDRMs, except K65R, were detected in HIV-1 subtype B isolates.. Conclusion: The high diversity of protease site TDRMs in the minority HIV-1 variants and prevalence of CRFs were remarkable in this study. All minority HIV-1 variants were missed by conventional sequencing. TDRM prevalence among minority variants appears to be decreasing over time at our center.

scholarly journals HIV-1 outcompetes HIV-2 in dually infected Senegalese individuals with low CD4+ cell counts

AIDS ◽  
2013 ◽  
Vol 27 (15) ◽  
pp. 2441-2450 ◽  
Author(s):  
Dana N. Raugi ◽  
Geoffrey S. Gottlieb ◽  
Papa S. Sow ◽  
Macoumba Toure ◽  
Fatima Sall ◽  
...  
Keyword(s):  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Cd4 Cell ◽  
Hiv 1

Characteristics allelic of Human Leukocyte Antigen class I genotype and association with viral load and CD4 cell count in HIV-1 infected patients, Hanoi 2014 – 2016

2021 ◽  
Vol 31 (4) ◽  
pp. 43-50
Author(s):  
Tran Thi Minh Tam ◽  
Nguyen Thuy Linh ◽  
Phan Ha My ◽  
Nguyen Thi Lan Anh
Keyword(s):  
Viral Load ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Cd4 Cell Count ◽  
Leukocyte Antigen ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Cd4 Cell ◽  
Hiv 1

Human Leukocyte Antigen (HLA) class I plays a regulatory role in cellular immune response to HIV-1 infection. The role of HLA alleles in HIV progression via viral load and CD4 cell count is well known. HLA class I is polymorphic and distributed differently by nation. This descriptive cross-sectional study was performed on 303 HIV-1 infected patients in 2014 - 2016, with aims to (i) characterize HLA class I genotype with 4-digit nomenclature and (ii) identify specifc alleles in correlate with CD4 cell counts and HIV viral load. 117 allele genotypes have been identifed, including 28 HLA-A alleles, 54 HLA-B alleles and 35 HLA-C alleles. The results showed that the most prevalent alleles in the population include A*11:01 (30.7%), B*15:02 (15.2%) and C*08:01 (17.1%). The frequency of haplotype created from these alleles is 8.4%. A*02:03, B*46:01 related to gender and ethnicity respectively. In conclusion, the study provided detailed pattern of HLA class I expression in a study population of HIV-1 infected patients and reported for the frst time the associated B*51:01, C*14:02 alleles associated to an increase in CD4 cell counts.

scholarly journals Early Postseroconversion CD4 Cell Counts Independently Predict CD4 Cell Count Recovery in HIV-1–Postive Subjects Receiving Antiretroviral Therapy

2011 ◽  
Vol 57 (5) ◽  
pp. 387-395 ◽  
Author(s):  
Hemant Kulkarni ◽  
Jason F Okulicz ◽  
Greg Grandits ◽  
Nancy F Crum-Cianflone ◽  
Michael L Landrum ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Cell Count ◽  
Cd4 Cell Count ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Cd4 Cell ◽  
Hiv 1 ◽  
Count Recovery

scholarly journals L74V increases the reverse transcriptase content of HIV-1 virions with non-nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and K101E+G190S, which results in increased fitness

2013 ◽  
Vol 94 (7) ◽  
pp. 1597-1607 ◽  
Author(s):  
Jiong Wang ◽  
Dongge Li ◽  
Robert A. Bambara ◽  
Hongmei Yang ◽  
Carrie Dykes
Keyword(s):  
Reverse Transcriptase ◽  
Resistance Mutation ◽  
Transcriptase Inhibitor ◽  
Rnase H ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Nnrti Resistance ◽  
Reverse Transcriptase Inhibitor ◽  
Subsequent Addition ◽  
Hiv 1

The fitness of non-nucleoside reverse transcriptase inhibitor (NNRTI) drug-resistant reverse transcriptase (RT) mutants of HIV-1 correlates with the amount of RT in the virions and the RNase H activity of the RT. We wanted to understand the mechanism by which secondary NNRTI-resistance mutations, L100I and K101E, and the nucleoside resistance mutation, L74V, alter the fitness of K103N and G190S viruses. We measured the amount of RT in virions and the polymerization and RNase H activities of mutant RTs compared to wild-type, K103N and G190S. We found that L100I, K101E and L74V did not change the polymerization or RNase H activities of K103N or G190S RTs. However, L100I and K101E reduced the amount of RT in the virions and subsequent addition of L74V restored RT levels back to those of G190S or K103N alone. We conclude that fitness changes caused by L100I, K101E and L74V derive from their effects on RT content.

Analysis of clinical AIDS‐free interval after CD4+ cell counts fall below 200 × 10 6 L −1 in Japanese Haemophiliacs infected with HIV‐1

Haemophilia ◽  
1998 ◽  
Vol 4 (1) ◽  
pp. 41-46
Author(s):  
Tatsunami ◽  
Mimaya ◽  
Meguro ◽  
Kuwabara ◽  
Yago ◽  
...  
Keyword(s):  
Cell Counts ◽  
Free Interval ◽  
Cd4 Cell Counts ◽  
Cd4 Cell ◽  
Hiv 1

scholarly journals HIV virological failure and drug resistance among injecting drug users receiving first-line ART in China

BMJ Open ◽  
2014 ◽  
Vol 4 (10) ◽  
pp. e005886 ◽  
Author(s):  
Xuebing Leng ◽  
Shujia Liang ◽  
Yanling Ma ◽  
Yonghui Dong ◽  
Wei Kan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Virological Failure ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Drug Users ◽  
Monitoring Network ◽  
Transcriptase Inhibitor ◽  
First Line ◽  
Cd4 Cell Count ◽  
Reverse Transcriptase Inhibitor ◽  
Cd4 Cell

ObjectiveTo explore HIV virological failure and drug resistance among injecting drug users (IDUs) receiving first-line antiretroviral treatment (ART) in China.DesignA series of cross-sectional surveys from 2003 to 2012 from the Chinese National HIV Drug Resistance (HIVDR) Surveillance and Monitoring Network.SettingChina.ParticipantsData were analysed by the Chinese National (HIVDR) Surveillance and Monitoring Network from 2003 to 2012. Demographic, ART and laboratory data (CD4+ cell count, viral load and drug resistance) were included. Factors associated with virological failure were identified by logistic regression analysis.Results929 of the 8556 individuals in the Chinese HIVDR database were IDUs receiving first-line ART. For these 929 IDUs, the median duration of treatment was 14 months (IQR 6.0–17.8). 193 of the 929 IDUs (20.8%) experienced virological failure (HIV viral load ≥1000 copies/mL). The prevalence of HIVDR among patients with virological failure was 38.9% (68/175). The proportion of patients with drug resistance to non-nucleoside reverse transcriptase inhibitor (NNRTIs), nucleoside reverse transcriptase inhibitor (NRTIs) and protease inhibitors (PIs) was 52.9%, 76.5% and 4.4%, respectively. Factors independently associated with virological failure include: ethnic minorities, junior high school education or less, farmers, self-reported missing doses in the past month, CD4 cell count at survey from 200 to 349 cells/mm3 or from 0 to 199 cells/mm3, and residence of Guangxi and Yunnan provinces.ConclusionsThe proportion of virological failure was high among IDUs receiving first-line ART in China. However, better treatment outcomes were observed in Guangxi and Yunnan, which indicates the importance of ART education and adherence to intervention, especially for patients who are farmers, minorities or have a poor educational background.

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