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The effects of HAART on the expression of MUC1 and P65 in a cervical cancer cell line, HCS-2

Thabethe KR, Adefolaju GA, Hosie MJ

Biomed Pharmacother, 2015 Apr;71:227-32.
PMID: 25960241 DOI: 10.1016/j.biopha.2015.03.001

Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24-hour treatment of a cervical cancer cell line, HCS-2, with drugs, which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one-way ANOVA followed by a Tukey-Kramer post-hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death; therefore, the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Matched MeSH terms: Antiretroviral Therapy, Highly Active*
Fulltext The man with bilateral nipple pain

Hong HC, Koh KC

Malays Fam Physician, 2013;8(3):43-45.
PMID: 25893059 MyJurnal

Figure 1 is a picture of a 48-year-old male patient who presents with progressive painful enlargement of the areolae of 10 months’ duration. There was no bleeding or nipple discharge. He was diagnosed with human immunodeficiency virus (HIV) infection 16 months ago and was initiated on antiretroviral therapy (ARV), which consisted of zidovudine, lamivudine and efavirenz. As his CD4 cell count at diagnosis was less than 200 cells/mm3, he was prescribed trimethoprim-sulphamethoxazole (Bactrim) for prophylaxis against pneumonia due to pneumocystis jirovecii. Physical examination was unremarkable except for bilateral breast enlargement and right-sided old shingles scar in the T4 dermatome distribution.

Matched MeSH terms: Antiretroviral Therapy, Highly Active
Fulltext The significance of HIV 'blips' in resource-limited settings: is it the same? analysis of the treat Asia HIV Observational Database (TAHOD) and the Australian HIV Observational Database (AHOD)

Kanapathipillai R, McManus H, Kamarulzaman A, Lim PL, Templeton DJ, Law M, et al.

PLoS One, 2014;9(2):e86122.
PMID: 24516527 DOI: 10.1371/journal.pone.0086122

INTRODUCTION: Magnitude and frequency of HIV viral load blips in resource-limited settings, has not previously been assessed. This study was undertaken in a cohort from a high income country (Australia) known as AHOD (Australian HIV Observational Database) and another cohort from a mixture of Asian countries of varying national income per capita, TAHOD (TREAT Asia HIV Observational Database).
METHODS: Blips were defined as detectable VL (≥ 50 copies/mL) preceded and followed by undetectable VL (<50 copies/mL). Virological failure (VF) was defined as two consecutive VL ≥50 copies/ml. Cox proportional hazard models of time to first VF after entry, were developed.
RESULTS: 5040 patients (AHOD n = 2597 and TAHOD n = 2521) were included; 910 (18%) of patients experienced blips. 744 (21%) and 166 (11%) of high- and middle/low-income participants, respectively, experienced blips ever. 711 (14%) experienced blips prior to virological failure. 559 (16%) and 152 (10%) of high- and middle/low-income participants, respectively, experienced blips prior to virological failure. VL testing occurred at a median frequency of 175 and 91 days in middle/low- and high-income sites, respectively. Longer time to VF occurred in middle/low income sites, compared with high-income sites (adjusted hazards ratio (AHR) 0.41; p<0.001), adjusted for year of first cART, Hepatitis C co-infection, cART regimen, and prior blips. Prior blips were not a significant predictor of VF in univariate analysis (AHR 0.97, p = 0.82). Differing magnitudes of blips were not significant in univariate analyses as predictors of virological failure (p = 0.360 for blip 50-≤1000, p = 0.309 for blip 50-≤400 and p = 0.300 for blip 50-≤200). 209 of 866 (24%) patients were switched to an alternate regimen in the setting of a blip.
CONCLUSION: Despite a lower proportion of blips occurring in low/middle-income settings, no significant difference was found between settings. Nonetheless, a substantial number of participants were switched to alternative regimens in the setting of blips.

Matched MeSH terms: Antiretroviral Therapy, Highly Active*
Three different patterns of CD4 recovery in a cohort of Chinese HIV patients following antiretroviral therapy - a five-year observational study

Naftalin CM, Wong NS, Chan DP, Wong KH, Reidpath DD, Lee SS

Int J STD AIDS, 2015 Oct;26(11):803-9.
PMID: 25281539 DOI: 10.1177/0956462414553826

To explore the heterogeneity of CD4 responses following highly active antiretroviral therapy, the patterns of CD4 recovery of HIV-1-infected Chinese patients who have been on their first antiretroviral regimen for ≥5 years were analysed. The CD4 trajectories were traced, smoothed and differentiated into three defined profiles. Half (56.3%) were 'satisfactory responders', with CD4 gain of >100 cells/μL and a peak of >350 cells/μL, plateauing before the end of Year 5. Thirty-three (24.4%) were 'continuing responders' whose CD4 rise persisted at Year 4-5. The remaining 26 (19.3%) were 'poor responders'. Presentation with AIDS before therapy was common not just among 'poor' but also paradoxically the 'continuing' responders. While a majority had responded well to antiretroviral therapy, older patients and those with AIDS diagnosis before initiation of therapy may never achieve a satisfactory level even with effective treatment. Categorization of HIV patients by their CD4 trajectory may support the prediction of immunological outcome over time, and ultimately inform treatment choices.

Matched MeSH terms: Antiretroviral Therapy, Highly Active*
Total resolution of ocular Kaposi sarcoma with different treatment approaches - a case series and review of literature

Yeak J, Iqbal T, Zahari M, Ismail F

Int J STD AIDS, 2019 07;30(8):802-809.
PMID: 31046617 DOI: 10.1177/0956462418825353
Matched MeSH terms: Antiretroviral Therapy, Highly Active
Fulltext Toxoplasmosis in HIV/AIDS: a living legacy

Nissapatorn V

Southeast Asian J. Trop. Med. Public Health, 2009 Nov;40(6):1158-78.
PMID: 20578449

Toxoplasmosis has historically been considered one of the most important opportunistic infections detected in HIV/AIDS patients. The prevalence rates of latent Toxoplasma infections in HIV-infected patients has been found to vary greatly from 3% to 97%. Prevalence has been found to be related to ethnicity, certain risk factors, and reactivation of toxoplasmosis. Prior to antiretroviral therapy, toxoplasmic encephalitis (TE) was the most common focal cerebral lesion detected in AIDS patients with Toxoplasma infection, occurring in approximately half of Toxoplasma-seropositive patients. Other forms of dissemination have also been reported in AIDS patients in sites such as the eyes, lungs, heart and spinal cord. Anti-Toxoplasma therapy and chemoprophylaxis have shown effectiveness in reducing the incidence of TE, while noncompliance has been identified as a cause of relapse in these settings. Toxoplasmosis is one of the most common neuropathological complications found at autopsy. Rapid progress in the development of highly active antiretroviral therapy (HAART) has changed the observed patterns with TE, for which there has been a marked decrease in overall incidence. Subsequently, TE has been found to be significantly associated with the so-called "neurological immune restoration inflammatory syndrome" (NIRIS). Toxoplasma screening programs are recommended for all newly diagnosed HIV-positive patients. Chemoprophylaxis should be considered in HIV-infected patients who have a CD4 < 200 cells/mm3, particularly in settings where resources are limited and there is not access to HAART. TE remains a cause of morbidity and mortality among AIDS patients.

Matched MeSH terms: Antiretroviral Therapy, Highly Active
Treatment of chronic hepatitis B in HIV co-infected patients

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: Antiretroviral Therapy, Highly Active*
Fulltext Trends in first-line antiretroviral therapy in Asia: results from the TREAT Asia HIV observational database

Boettiger DC, Kerr S, Ditangco R, Merati TP, Pham TT, Chaiwarith R, et al.

PLoS One, 2014;9(9):e106525.
PMID: 25184314 DOI: 10.1371/journal.pone.0106525

Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes.

Matched MeSH terms: Antiretroviral Therapy, Highly Active/adverse effects; Antiretroviral Therapy, Highly Active/methods*
Fulltext Use and Outcomes of Antiretroviral Monotherapy and Treatment Interruption in Adolescents With Perinatal HIV Infection in Asia

Bartlett AW, Lumbiganon P, Kurniati N, Sudjaritruk T, Mohamed TJ, Hansudewechakul R, et al.

J Adolesc Health, 2019 11;65(5):651-659.
PMID: 31395514 DOI: 10.1016/j.jadohealth.2019.05.025

PURPOSE: Antiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort.
METHODS: Regional Asian data (2001-2016) were analyzed to describe PHIVA who experienced ≥2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption.
RESULTS: Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to ≥2 combination ART regimens. Treatment interruption was associated with CD4 count <350 cells/μL, HIV RNA ≥1,000 copies/mL, ART adverse event, and commencing ART age ≥10 years compared with age <3 years. WHO clinical stage III/IV 1-year event-free survival was 96% and 85% for monotherapy and treatment interruption cohorts, respectively. WHO immunologic stage III/IV 1-year event-free survival was 52% for both cohorts. Those who experienced monotherapy or treatment interruption for more than 6 months had worse immunologic and virologic outcomes.
CONCLUSIONS: Until challenges of treatment adherence, engagement in care, and combination ART durability/tolerability are met, monotherapy and treatment interruption will lead to poor long-term outcomes.

Matched MeSH terms: Antiretroviral Therapy, Highly Active