Displaying publications 1 - 20 of 26 in total

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  1. Zain RM, Ibrahim N, Ismail S, Suppiah J, Mat Rahim NA, Thayan R
    Asian Pac J Trop Med, 2017 Jan;10(1):75-78.
    PMID: 28107870 DOI: 10.1016/j.apjtm.2016.12.005
    OBJECTIVE: To determine drug resistance mutations and the HIV-1 subtypes among antiretroviral treatment naive HIV-1 patients in Peninsular Malaysia.

    METHODS: A total of 45 samples from four hospitals that provide HIV viral load services were subjected to the amplification of the protease and two third of reverse transcriptase regions of the pol gene by RT-PCR and Sanger sequencing. Drug resistance mutation (DRM) interpretation reports the presence of mutations related to protease inhibitors (PIs), Nucleoside reverse-transcriptase inhibitors (NRTI) and Non-nucleoside reverse-transcriptase inhibitors (NNRTI) based on analysis using Stanford HIV database program.

    RESULTS: DRMs were identified in 35% of patients, among which 46.7% of them showed minor resistance to protease inhibitor with A71V and L10l were the commonest DRMs detected. About 21.4% and 50.0% of patients had mutations to NRTIs and NNRTIs, respectively. CRF01_AE was found to be the predominant HIV-1 subtype.

    CONCLUSIONS: These findings have served as an initial crucial data in determining the prevalence of transmitted HIV-1 drug resistance for the country. However, more samples from various parts of the country need to be accumulated and analyzed to provide overall HIV-1 drug resistance in the country.

    Matched MeSH terms: Reverse Transcriptase Inhibitors
  2. Wittawatmongkol O, Mohamed TJ, Le TP, Ung V, Maleesatharn A, Hansudewechakul R, et al.
    Journal of virus eradication, 2015 06 30;1(3):192-195.
    PMID: 27076917
    After a median of 115.9 months of follow-up, 90% of 206 HIV-1-infected children in a cohort in Asia who initiated antiretroviral treatment (ART) with mono or dual nucleoside reverse transcriptase inhibitors were alive and had comparable immunological and virological outcomes as compared to the 1,915 children who had started with highly active antiretroviral regimens. However, these children had higher rates of treatment-related adverse events, opportunistic infections, and cumulative mortality, and were more likely to require protease inhibitor-containing regimens or other more novel ART-based regimens.
    Matched MeSH terms: Reverse Transcriptase Inhibitors
  3. Sudjaritruk T, Teeraananchai S, Kariminia A, Lapphra K, Kumarasamy N, Fong MS, et al.
    J Int AIDS Soc, 2020 07;23(7):e25550.
    PMID: 32628816 DOI: 10.1002/jia2.25550
    INTRODUCTION: The clinical relevance of low-level viraemia (LLV) and virological outcomes among children living with HIV (CLHIV) remains controversial. This study aimed to determine the impact of LLV on virological failure (VF) among Asian CLHIV on first-line combination antiretroviral therapy (cART).

    METHODS: CLHIV aged <18 years, who were on first-line cART for ≥12 months, and had virological suppression (two consecutive plasma viral load [pVL] <50 copies/mL) were included. Those who started treatment with mono/dual antiretroviral therapy, had a history of treatment interruption >14 days, or received treatment and care at sites with a pVL lower limit of detection >50 copies/mL were excluded. LLV was defined as a pVL 50 to 1000 copies/mL, and VF as a single pVL >1000 copies/mL. Baseline was the time of the second pVL 

    Matched MeSH terms: Reverse Transcriptase Inhibitors/therapeutic use
  4. Sim SM, Hoggard PG, Sales SD, Phiboonbanakit D, Hart CA, Back DJ
    AIDS Res Hum Retroviruses, 1998 Dec 20;14(18):1661-7.
    PMID: 9870320
    Zidovudine (ZDV) is converted to its active triphosphate (ZDVTP) by intracellular kinases. The intermediate ZDV monophosphate (ZDVMP) is believed to play a major role in ZDV toxicity. Manipulation of ZDV phosphorylation is a possible therapeutic strategy for altering the risk-benefit ratio. Here we investigate whether combining RBV with ZDV is able to modulate efficacy and toxicity of ZDV. We have measured the intracellular activation of ZDV (0.3 microM) in the absence and presence of ribavirin (RBV; 2 and 20 microM) in Molt 4 and U937 cells. MTT cytotoxicity of ZDV (10-1000 microM) was also measured with and without RBV (2 microM) in Molt 4 and U937 cells. Measurement of endogenous deoxythymidine triphosphate (dTTP) allowed investigation of the dTTP/ZDVTP ratio. The antiviral efficacy of ZDV in combination with RBV (2 microM) was assessed by HIV p24 antigen measurements. In the presence of RBV (2 and 20 microM) a decrease in total ZDV phosphates was observed, owing mainly to an effect primarily on ZDVMP rather than the active ZDVTP. RBV also increased endogenous dTTP pools in both cell types, resulting in an increase in the dTTP/ZDVTP ratio. ZDV alone significantly reduced p24 antigen production, with an IC50 of 0.34 microM. Addition of RBV increased the IC50 approximately fivefold (1.52 microM). However, at higher concentrations of ZDV (10 and 100 microM) the antagonistic effect of RBV (2 microM) on ZDV was lost. The RBV-mediated decrease in ZDVMP may explain the reduction in ZDV toxicity when combined with RBV (2 microM). Cytotoxicity of ZDV was reduced in the presence of RBV (2 microM) at all concentrations in both cell lines, probably owing to saturation of ZDVTP formation. The interaction of ZDV and RBV is concentration dependent.
    Matched MeSH terms: Reverse Transcriptase Inhibitors/adverse effects; Reverse Transcriptase Inhibitors/pharmacology*
  5. Ross J, Jiamsakul A, Kumarasamy N, Azwa I, Merati TP, Do CD, et al.
    HIV Med, 2021 Mar;22(3):201-211.
    PMID: 33151020 DOI: 10.1111/hiv.13006
    OBJECTIVES: To assess second-line antiretroviral therapy (ART) virological failure and HIV drug resistance-associated mutations (RAMs), in support of third-line regimen planning in Asia.

    METHODS: Adults > 18 years of age on second-line ART for ≥ 6 months were eligible. Cross-sectional data on HIV viral load (VL) and genotypic resistance testing were collected or testing was conducted between July 2015 and May 2017 at 12 Asia-Pacific sites. Virological failure (VF) was defined as VL > 1000 copies/mL with a second VL > 1000 copies/mL within 3-6 months. FASTA files were submitted to Stanford University HIV Drug Resistance Database and RAMs were compared against the IAS-USA 2019 mutations list. VF risk factors were analysed using logistic regression.

    RESULTS: Of 1378 patients, 74% were male and 70% acquired HIV through heterosexual exposure. At second-line switch, median [interquartile range (IQR)] age was 37 (32-42) years and median (IQR) CD4 count was 103 (43.5-229.5) cells/µL; 93% received regimens with boosted protease inhibitors (PIs). Median duration on second line was 3 years. Among 101 patients (7%) with VF, CD4 count > 200 cells/µL at switch [odds ratio (OR) = 0.36, 95% confidence interval (CI): 0.17-0.77 vs. CD4 ≤ 50) and HIV exposure through male-male sex (OR = 0.32, 95% CI: 0.17-0.64 vs. heterosexual) or injecting drug use (OR = 0.24, 95% CI: 0.12-0.49) were associated with reduced VF. Of 41 (41%) patients with resistance data, 80% had at least one RAM to nonnucleoside reverse transcriptase inhibitors (NNRTIs), 63% to NRTIs, and 35% to PIs. Of those with PI RAMs, 71% had two or more.

    CONCLUSIONS: There were low proportions with VF and significant RAMs in our cohort, reflecting the durability of current second-line regimens.

    Matched MeSH terms: Reverse Transcriptase Inhibitors
  6. Peksheva O, Kuzovatova E, Parfenova O, Zaytseva N
    Viruses, 2022 Aug 27;14(9).
    PMID: 36146704 DOI: 10.3390/v14091898
    The increasing number of HIV-infected people who are receiving ART, including those with low adherence, is causing the spread of HIV drug resistance (DR). A total of 1396 plasma samples obtained from treatment-experienced patients from the Volga federal district (VFD), Russia, were examined to investigate HIV DR occurrence. The time periods 2008−2015 and 2016−2019 were compared. Fragmentary Sanger sequencing was employed to identify HIV resistance to reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs) using an ABI 3500XL genetic analyzer, a ViroSeq™ HIV-1 genotyping system (Alameda, CA, USA) and AmpliSense HIV-Resist-Seq reagent kits (Moscow, Russia). In 2016−2019, HIV DR was detected significantly more often than in 2008−2015 (p < 0.01). Mutations to RTIs retained leading positions in the structure of DR. Frequencies of resistance mutations to nucleoside and non-nucleoside RTIs (NRTIs and NNRTIs) in the spectra of detected mutations show no significant differences. Resistance to NRTIs after 2016 began to be registered more often as a part of multidrug resistance (MDR), as opposed to resistance to a single class of antiretrovirals. The frequency of DR mutations to PIs was low, both before and after 2016 (7.9% and 6.1% in the spectrum, respectively, p > 0.05). MDR registration rate became significantly higher from 2008 to 2019 (17.1% to 72.7% of patients, respectively, p < 0.01). M184V was the dominant replacement in all the years of study. A significant increase in the frequency of K65R replacement was revealed. The prevalence of integrase strand transfer inhibitor (INSTI) resistance mutations remains to be investigated.
    Matched MeSH terms: Reverse Transcriptase Inhibitors/pharmacology; Reverse Transcriptase Inhibitors/therapeutic use
  7. Patil AD, Freyer AJ, Eggleston DS, Haltiwanger RC, Bean MF, Taylor PB, et al.
    J Med Chem, 1993 Dec 24;36(26):4131-8.
    PMID: 7506311
    As part of a search for novel inhibitors of HIV-1 reverse transcriptase, the acetone extract of the giant African snail, Achatina fulica, was shown to be active. Fractionation of the extract yielded inophyllums A, B, C, and E and calophyllolide (1a, 2a, 3a, 3b, and 6), previously isolated from Calophyllum inophyllum Linn., a known source of nutrition for A. fulica. From a methanol/methylene chloride extract of C. inophyllum, the same natural products in considerably greater yield were isolated in addition to a novel enantiomer of soulattrolide (4), inophyllum P (2b), and two other novel compounds, inophyllums G-1 (7) and G-2 (8). The absolute stereochemistry of inophyllum A (1a) was determined to be 10(R), 11(S), 12(S) from a single-crystal X-ray analysis of its 4-bromobenzoate derivative, and the relative stereochemistries of the other inophyllums isolated from C. inophyllum were established by a comparison of their 1H NMR NOE values and coupling constants to those of inophyllum A (1a). Inophyllums B and P (2a and 2b) inhibited HIV reverse transcriptase with IC50 values of 38 and 130 nM, respectively, and both were active against HIV-1 in cell culture (IC50 of 1.4 and 1.6 microM). Closely related inophyllums A, C, D, and E, including calophyllic acids, were significantly less active or totally inactive, indicating certain structural requirements in the chromanol ring. Altogether, 11 compounds of the inophyllum class were isolated from C. inophyllum and are described together with the SAR of these novel anti-HIV compounds.
    Matched MeSH terms: Reverse Transcriptase Inhibitors*
  8. Papot E, Jacoby S, Arlinda D, Avihingsanon A, Azwa I, Borok M, et al.
    HIV Res Clin Pract, 2022 Jul 19;23(1):37-46.
    PMID: 35938597
    A rapidly changing landscape of antiretrovirals and their procurement at scale has permitted the evaluation of new optimised second-line antiretroviral therapy (ART) in low- and middle-income countries. D2EFT is an open-label randomised controlled non-inferiority phase IIIB/IV trial in people living with HIV-1 (PWH) whose first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART is failing. At inception, it compared a standard of care of boosted darunavir with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) to the novel NRTI-sparing regimen of boosted darunavir with dolutegravir. Implemented in 2017, participating sites were across Africa, Asia and Latin America. Around the time of implementation, the World Health Organization updated its treatment guidelines and recommended scaling up tenofovir disoproxil fumarate-lamivudine-dolutegravir (TLD). This situation pushed D2EFT investigators to consider the impact of the roll-out of TLD on the D2EFT research question. The protocol team agreed it was important to study TLD in second-line when an NNRTI regimen was failing, and focused on options to expedite the work by studying the question within the existing trial and network. All key issues (statistical, programmatic and financial) were reviewed to assess the benefits and risks of adding a third arm to the ongoing study, as opposed to developing a new randomised clinical trial with the same control arm and within the same network. The development of a new trial was deemed to be longer than adding a third arm, and to create a challenging situation with two competing clinical trials at the same sites which would slow down recruitment and impair both trials. On the other hand, adding a third arm would be demanding in terms of operationalisation, increased sample size and statistical biases to control. The optimal strategy was deemed to be the addition of a third arm, arriving retrospectively at a simplified multi-arm multi-stage clinical trial design to achieve statistical validity. The D2EFT study maintains additional value in a quickly evolving second-line ART strategy allowed by the progress in global access to ART.
    Matched MeSH terms: Reverse Transcriptase Inhibitors/therapeutic use
  9. Mustafa S, Hassan NB, Tan SC, Ab Rahman AK, Low LL, Wan Yusuf WN
    Turk J Med Sci, 2016 Dec 20;46(6):1875-1881.
    PMID: 28081342 DOI: 10.3906/sag-1503-116
    BACKGROUND/AIM: Nevirapine is a reverse-transcriptase inhibitor widely used in combination therapy to treat HIV infection. Nevirapine is extensively metabolized in the liver and CYP2B6 is mainly responsible for oxidation of 3-hydroxynevirapine (3-OH NVP). This study aims to explore CYP2B6 activity by measuring 2-hydroxynevirapine (2-OH NVP) and 3-OH NVP in plasma and to identify factors associated with nevirapine pharmacokinetic parameters.

    MATERIALS AND METHODS: A total of 112 patients were recruited and treated with nevirapine-based antiretroviral therapy. Plasma nevirapine and metabolite concentrations were assayed using high-performance liquid chromatography via liquid-liquid extraction.

    RESULTS: Thirty-nine (34.8%) of the patients had no 3-OH NVP detected in their plasma while 2-OH NVP was detected in all patients. Metabolite concentrations were low compared to nevirapine. Positive correlations were observed between nevirapine and its metabolites, 2-OH NVP (P < 0.01) and 3-OH NVP (P = 0.012). Nevirapine concentration was decreased when concomitantly administered with methadone. Univariate analysis showed that ALT level, AST level, and detection of 3-OH NVP were associated with nevirapine pharmacokinetic parameters.

    CONCLUSION: The variability of nevirapine pharmacokinetic parameters was caused by liver enzymes and the presence of 3-OH NVP metabolites. The presence of 3-OH NVP can probably be used to distinguished CYP2B6 activity and efficacy of nevirapine in patients with HIV infection.

    Matched MeSH terms: Reverse Transcriptase Inhibitors
  10. Martin A, Moore C, Mallon PW, Hoy J, Emery S, Belloso W, et al.
    AIDS, 2013 Sep 24;27(15):2403-11.
    PMID: 23921615 DOI: 10.1097/01.aids.0000432534.47217.b4
    To compare changes over 48 weeks in bone mineral density (BMD) between participants randomized to lopinavir/ritonavir (LPV/r) + raltegravir (RAL) or LPV/r + 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) as second line therapy.
    Matched MeSH terms: Reverse Transcriptase Inhibitors/administration & dosage; Reverse Transcriptase Inhibitors/adverse effects*
  11. Leung N
    Med J Malaysia, 2005 Jul;60 Suppl B:22-7.
    PMID: 16108169
    Nucleot(s)ide analogues are making milestones in the treatment of chronic hepatitis B (CHB) as safe oral therapy. FDA approved lamivudine in adult patients in 1998, adefovir dipivoxil in 2002, and entecavir in March 2005. Lamivudine is effective in viral suppression, ALT normalization, and improvement in histology in both HBeAg positive and HBeAg negative / HBV DNA positive patients. HBeAg seroconversion rates correlate directly with pretreatment ALT levels at 18-30% after one year of therapy. Hepatitis flares may occur if lamivudine is stopped before HBeAg seroconversion. Lamivudine resistant YMDD mutants emerge at a rate of 15-20% per year of therapy; often associated with the rebound viraemia, relapse of hepatitis or even hepatic decompensation. Durability of response off lamivudine therapy is not satisfactory and may be dependent on duration of therapy post-seroconversion. Lamivudine is well tolerated with few serious adverse events, even in patients with decompensated cirrhosis. Long term therapy in viraemic patients with advanced fibrosis or cirrhosis delays clinical progression. Adefovir dipivoxil is an oral prodrug of adefovir. 10 mg daily is effective in suppressing both wild-type HBV and YMDD mutants, normalising ALT and improving histology. Adefovir dipivoxil has been shown to be well tolerated in longterm therapy. Renal toxicity reported in higher dosages is rarely seen except among patients with creatinine clearance less than 50 ml/min. Adefovir resistance may emerge and the overall rate is much lower than lamivudine, reaching 18% after 4 years of therapy. Adefovir-resistant mutants (rt N236T) are susceptible to lamivudine and entecavir. Little data is available for durability of response off therapy. Entecavir is an oral nucleoside analogue with a recommended dosage of 0.5 mg daily for nucleoside-naive patients, and 1 mg daily for lamivudine-refractory patients. It is a potent antiviral and may also reduced intrahepatitic cccDNA. Entecavir resistance so far has only been detected in lamivudine resistant patients in the one-year studies. Patient counseling is very important to decide on the choice among available therapeutic options. The assessment of the risks/benefits of each option should be carefully explained to individual patient.
    Matched MeSH terms: Reverse Transcriptase Inhibitors/therapeutic use*
  12. Lau GK
    Med J Malaysia, 2005 Jul;60 Suppl B:57-62.
    PMID: 16108175
    Matched MeSH terms: Reverse Transcriptase Inhibitors/therapeutic use*
  13. Koh KC, Lee WY, Eh ZW, Ismail NJ, Tee PS, Othman A, et al.
    Med J Malaysia, 2013 Jun;68(3):249-52.
    PMID: 23749016
    Efavirenz is a non-nucleoside reverse transcriptase inhibitor used in combination with other drugs for the treatment of patients with HIV infection. Efavirenz has been reported to cause a positive urine cannabis test reaction which may create problems between HIV-infected patients on Efavirenz and law enforcement agencies. Doctors are at loss whether to issue documents certifying the potential false positive urine cannabis test with Efavirenz to patients. We investigated if the urine of HIV-infected patients on Efavirenz caused a positive urine cannabis test using the AxSYM Cannabinoids Assay®. Urine samples from 51 eligible patients on Efavirenz were tested for cannabis. All tested negative except for one who had used cannabis the day before. Efavirenz does not cause false positive urine cannabis test with the AxSYM Cannabinoids Assay®. Certification documents from doctors are therefore unnecessary.
    Matched MeSH terms: Reverse Transcriptase Inhibitors
  14. Kim JH, Jiamsakul A, Kiertiburanakul S, Huy BV, Khusuwan S, Kumarasamy N, et al.
    PLoS One, 2022;17(3):e0264157.
    PMID: 35353840 DOI: 10.1371/journal.pone.0264157
    The use of holding regimens for people living with HIV (PLWH) without effective antiretroviral options can have effects on outcomes and future treatment options. We aimed to investigate the use of holding regimens for PLWH in Asian countries. Data from adults enrolled in routine HIV care in IeDEA Asia-Pacific cohorts were included. Individuals were considered to be on holding regimen if they had been on combination antiretroviral therapy for at least 6 months, had two confirmed viral loads (VL) ≥1000 copies/mL, and had remained on the same medications for at least 6 months. Survival time was analyzed using Fine and Gray's competing risk regression. Factors associated with CD4 changes and VL <1000 copies/mL were analyzed using linear regression and logistic regression, respectively. A total of 425 PLWH (72.9% male; 45.2% high-income and 54.8% low-to-middle-income country) met criteria for being on a holding regimen. From high-income countries, 63.0% were on protease inhibitors (PIs); from low-to-middle-income countries, 58.4% were on non-nucleoside reverse transcriptase inhibitors (NNRTIs); overall, 4.5% were on integrase inhibitors. The combination of lamivudine, zidovudine, and efavirenz was the most commonly used single regimen (n = 46, 10.8%), followed by lamivudine, zidovudine, and nevirapine (n = 37, 8.7%). Forty-one PLWH (9.7%) died during follow-up (mortality rate 2.0 per 100 person-years). Age >50 years compared to age 31-40 years (sub-hazard ratio [SHR] 3.29, 95% CI 1.45-7.43, p = 0.004), and VL ≥1000 copies/ml compared to VL <1000 copies/mL (SHR, 2.14, 95% CI 1.08-4.25, p = 0.029) were associated with increased mortality, while higher CD4 counts were protective. In our Asia regional cohort, there was a diversity of holding regimens, and the patterns of PI vs. NNRTI use differed by country income levels. Considering the high mortality rate of PLWH with holding regimen, efforts to extend accessibility to additional antiretroviral options are needed in our region.
    Matched MeSH terms: Reverse Transcriptase Inhibitors/therapeutic use
  15. Hashim H, Sahari NS, Sazlly Lim SM, Hoo FK
    Iran Red Crescent Med J, 2015 Oct;17(10):e19546.
    PMID: 26568856 DOI: 10.5812/ircmj.19546
    INTRODUCTION: The introduction of highly active antiretroviral therapy (HAART), in 1996, has resulted in marked reductions in the rate of illness and death, due to HIV infection. The HAART has transformed HIV infection into a manageable chronic disease. However, although many regimens lower plasma viral load, to below the limit of detection, in most patients, maintaining viral load suppression remains challenging, because of adverse effects and toxicity in the long term, which can lead to non-adherence, virologic failure and drug resistance. Although rare, lactic acidosis often develops fatal complications, as reported in several human immunodeficiency virus infected patients treated with nucleoside reverse transcriptase inhibitors (NRTIs). The purpose of this paper is to report a case of tenofovir induced lactic acidosis and review the literature.

    CASE PRESENTATION: A 52-year-old Malay gentleman, with hepatitis C virus and HIV infection was admitted to the intensive care unit for severe lactic acidosis, with concurrent Escherichia coli bacteremia with multiorgan dysfunction. The patient was started on highly active antiretroviral therapy, which included tenofovir, 5 weeks before presentation. Antimicrobial therapy, continuous veno-venous hemofiltration, and other supportive treatments were instituted. However, the patient eventually succumbed to his illness.

    CONCLUSIONS: It is essential for clinicians to be able to recognize the signs and symptoms of lactic acidosis in NRTIs treated HIV patients, as an early diagnosis is important to institute treatment.

    Matched MeSH terms: Reverse Transcriptase Inhibitors
  16. Hanna L
    BETA, 1999 Apr;12(2):8-9.
    PMID: 11366704
    Matched MeSH terms: Reverse Transcriptase Inhibitors/therapeutic use*
  17. Han WM, Law MG, Choi JY, Ditangco R, Kumarasamy N, Chaiwarith R, et al.
    HIV Med, 2022 Mar;23(3):274-286.
    PMID: 34816562 DOI: 10.1111/hiv.13211
    OBJECTIVES: We investigated weight changes following antiretroviral therapy (ART) initiation, the development of metabolic syndrome (MetS) and its association with all-cause mortality among Asian adults living with HIV.

    METHODS: Participants enrolled in a regional Asian HIV-infected cohort with weight and height measurements at ART initiation were eligible for inclusion in the analysis. Factors associated with weight changes and incident MetS (according to the International Diabetic Federation (IDF) definition) were analysed using linear mixed models and Cox regression, respectively. Competing-risk regression models were used to investigate the association of MetS with all-cause mortality.

    RESULTS: Among 4931 people living with HIV (PLWH), 66% were male. At ART initiation, the median age was 34 [interquartile range (IQR) 29-41] years, and the median (IQR) weight and body mass index (BMI) were 55 (48-63) kg and 20.5 (18.4-22.9) kg/m2 , respectively. At 1, 2 and 3 years of ART, overall mean (± standard deviation) weight gain was 2.2 (±5.3), 3.0 (±6.2) and 3.7 (±6.5) kg, respectively. Participants with baseline CD4 count ≤ 200 cells/µL [weight difference (diff) = 2.2 kg; 95% confidence interval (CI) 1.9-2.5 kg] and baseline HIV RNA ≥ 100 000 HIV-1 RNA copies/mL (diff = 0.6 kg; 95% CI 0.2-1.0 kg), and those starting with integrase strand transfer inhibitor (INSTI)-based ART (diff = 2.1 kg; 95% CI 0.7-3.5 kg vs. nonnucleoside reverse transcriptase inhibitors) had greater weight gain. After exclusion of those with abnormal baseline levels of MetS components, 295/3503 had incident MetS [1.18 (95% CI 1.05-1.32)/100 person-years (PY)]. The mortality rate was 0.7 (95% CI 0.6-0.8)/100 PY. MetS was not significantly associated with all-cause mortality in the adjusted model (P = 0.236).

    CONCLUSIONS: Weight gain after ART initiation was significantly higher among those initiating ART with lower CD4 count, higher HIV RNA and an INSTI-based regimen after controlling for baseline BMI. Greater efforts to identify and manage MetS among PLWH are needed.

    Matched MeSH terms: Reverse Transcriptase Inhibitors/therapeutic use
  18. Guan R
    Med J Malaysia, 2005 Jul;60 Suppl B:52-6.
    PMID: 16108174
    In the Asia Pacific region Human Immunodeficiency virus (HIV) is often acquired in individuals already infected with hepatitis B virus (HBV). The immune suppression caused by HIV infection reduces cellular immune response against HBV and liver inflammation may improve, but the risk of developing cirrhosis is not. HBV infection does not affect the progression of HIV disease. Anti-retroviral agents may be directly hepatotoxic and cause ALT elevations in patients with chronic hepatitis. Highly active anti-retroviral therapy (HAART) improves immunity and as cytotoxic lymphocyte responses improve, hepatitis flares can occur, usually r within 3 months of initiation of HAART. These hepatitis flares may be followed by normalization of ALT and clearance of HBVDNA. If lamivudine is included in the HAART regime, hepatitis flares may not occur till late and these late flares signal the development of lamivudine resistant HBV strains (90% of HBV/HIV co-infection). Treatment options for chronic HBV infection include interferon (IFN), and nucleoside analogues. Lamivudine, adefovir dipivoxil, tenofovir disoproxil fumarate (DF) are nucleoside analogues with activity against both HBVDNA polymerase and HIV reverse transcriptase. The latter two compounds have added activity against lamivudine resistant HBVDNA. Lamivudine should be avoided in the initial treatment of both hepatitis B as well as HIV because of the high incidence of resistance. Interferon should be considered first for treatment of HBV in HIV co-infected individuals and is usually unsuccessful in the later stages of HIV infection when immune suppression is extreme. As new and improved agents in HAART continue to prolong survival, the use of liver transplantation for cirrhotic patients co-infected with HIV and HBV may increase.
    Matched MeSH terms: Reverse Transcriptase Inhibitors/pharmacology; Reverse Transcriptase Inhibitors/therapeutic use*
  19. Gill MSA, Hassan SS, Ahemad N
    Eur J Med Chem, 2019 Oct 01;179:423-448.
    PMID: 31265935 DOI: 10.1016/j.ejmech.2019.06.058
    HIV infection is a major challenge to mankind and a definitive cure or a viable vaccine for HIV is still elusive. HIV-1 is constantly evolving and developing resistant against clinically used anti-HIV drugs thus posing serious hurdles in the treatment of HIV infection. This prompts the need to developed new anti-HIV drugs; preferentially adopting intelligent ways to counteract an evolving virus. Highly Active Anti-Retroviral Therapy (HAART): a strategy involving multiple targeting through various drugs has proven beneficial in the management of AIDS. However, it is a complex regimen with high drug load, increased risk of drug interactions and adverse effects, which lead to poor patient compliance. Reverse transcriptase (RT) and Integrase (IN) are two pivotal enzymes in HIV-1 lifecycle with high structural and functional analogy to be perceived as drug-able targets for novel dual-purpose inhibitors. Designed multi-functional ligand (DML) is a modern strategy by which multiple targets can be exploited using a single chemical entity. A single chemical entity acting on multiple targets can be much more effective than a complex multi-drug regimen. The development of such multifunctional ligands is highly valued in anti-HIV drug discovery with the proposed advantage of being able to stop two or more stages of viral replication cycle. This review will encompass the evolution of the RT-IN dual inhibitory scaffolds reported so far and the contribution made by the leading research groups over the years in this field.
    Matched MeSH terms: Reverse Transcriptase Inhibitors/pharmacology*; Reverse Transcriptase Inhibitors/chemistry
  20. Gane E
    Med J Malaysia, 2005 Jul;60 Suppl B:88-9.
    PMID: 16108183
    Matched MeSH terms: Reverse Transcriptase Inhibitors/therapeutic use
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