Factors of Adherence to Concurrent Tuberculosis Treatment and Antiretroviral Therapy among HIV-TB Co-Infected Individuals in the East Region, Cameroon in the COVID-19 Era: A Retrospective Cohort Study

Context/Objectives: Tuberculosis (TB) and HIV co-infection is a serious health problem in Cameroon. The problems associated with poor adherence to treatment are on the increase worldwide. This problem can be observed in all situations where patients are required to administer their own medication, whatever the type of illness. The general objective of this study was to assess the factors affecting adherence to treatment among HIV-TB co-infected patients in health facilities in the East Region in the COVID context. Method: A retrospective cohort study before and during COVID-19 was conducted in HIV care units in 13 health districts in the East Region of Cameroon. Data were collected using a questionnaire recorded in the Kobo Collect android application, analyzed using SPSS version 25 software and plotted using Excel. Results: The pre-COVID-19 cohort compared to the during-COVID-19 cohort had a 1.90 risk of not adhering to treatment (OR: 1.90, CI {1.90 - 3.37}) and the difference was statistically significant at the 5% level (p-value = 0.029). Frequency of adherence was 65.4% (140/214). Adherence before COVID-19 was 56.9% whereas during COVID-19, it was 74.3%. Conclusion: The implementation of targeted interventions in the COVID-19 context, using evidence-based data and integrating the individual needs of HIV-TB co-infected patients, improved adherence to concurrent anti-tuberculosis treatment and antiretroviral therapy during the COVID-19 Era.

Factors Associated with HIV/Tuberculosis Coinfection among People Living with HIV after Initiation of Antiretroviral Treatment in Lingwala Health Zone from 2021 to 2023

Context and objective: Around 8% of incident cases of tuberculosis (TB) were reported among people living with HIV worldwide in 2022. Tuberculosis is the leading cause of death among people living with HIV. Africa accounts for the majority of co-infection episodes, with over 50% of cases in some parts of southern Africa. In the Democratic Republic of Congo (DRC), around 9% of persons living with HIV (PLHIV) develop TB and 11% of TB patients are infected with HIV. The DRC is one of the 30 countries in the world bearing the brunt of co-infection. Despite the efforts made by countries to improve access to antiretroviral traitement (ART), TB remains a major problem among people living with HIV. The Lingwala Health Zone in the provincial city of Kinshasa recorded a large number of cases of HIV/TB co-infection during the study period. The aim of this study was to determine the factors associated with HIV/TB co-infection among PLHIV on ART in the Lingwala health zone (HZ) in Kinshasa. Methods: This was a case-control study conducted in the state-run HIV care facilities in the Lingwala health district among PLHIV who had visited the health facilities during the period 2021-2023. Cases were coinfected patients and controls were PLHIV who had not developed tuberculosis during the study period. Results: A total of 281 PLHIV were enrolled in the study, with 70 cases and 211 controls. Factors associated with HIV/TB co-infection after multivariate analysis were viral load (OR = 5.34;95% CI;1.8-15.8, p = 0.005). History of tuberculosis (OR = 20.84;95% CI;8.6-50.3, p -85.0, p = 0.005) and BMI Conclusion: The results of this study indicate that the detection of these enumerated factors should prompt providers to actively search for tuberculosis with a view to organising early management.

Immunovirological Discordance and Associated Factors among People Living with HIV under Antiretroviral Treatment at Hôpital de Jour de Donka, Guinea

The antiretroviral treatment (ART) has significantly reduced the number of new HIV/AIDS infections and related deaths. However, cases of immunovirological discordance (IVD) are found in various locations. The objective of this study was to determine the profile of People living with HIV (PLHIV) with IVD and to identify associated factors. We conducted a cross-sectional study based on the records of PLHIV under ART for at least 6 months, followed at Hpital de Jour Donka from 2015 to 2017, and having both viral load (CV) and CD4 T-cell count. Prevalence of IVD was 34.57%, with 23.87% for immunological discordance (ID) and 10.7% for virological discordance (VD). Females were predominant (66.26%), and male gender influenced IVD with a statistically significant difference (p = 0.006) and was associated with VD (p = 0.007). The average age was 38.77 11.30 years. PLHIV were classified at WHO stages 3 and 4 (86.01%). The median initial haemoglobin level was 11.5 g/L [3.2 - 12]. The mean initial CD4 T-cell count was 272.84 cells/mm3 201.6. The median initial viral load (VL) was 147,337 copies/mL [1092 - 31,675,000]. The initial CD4 T-cell count 3 was associated with IVD with a statistically significant difference (p = 0.0009) and correlated with ID (p = 0.000). Prurigo was associated with IVD with a statistically significant difference (p = 0.003). Cerebral toxoplasmosis was not associated with IVD but was associated with ID (p = 0.04). This study allowed us to describe the profile of PLHIV with IVD. The main associated factors were male gender, initial CD4 T-cell count 3, toxoplasmosis, prurigo, and herpes zoster.

Factors Associated with Antiretroviral Therapy Defaulting among Adult Patients Receiving Care at Chikankata Mission Hospital, Chikankata District, Zambia

Background: Defaulting on antiretroviral therapy has been identified as the most important factor contributing to the antiretroviral therapy failure rate. This study aimed to investigate factors associated with defaulting on antiretroviral therapy among adult patients receiving care at Chikankata Mission Hospital antiretroviral therapy clinic. Method: Cross-sectional analytical study on 385 participants selected by a computer generated random numbers technique of simple random sampling from among the patients receiving antiretroviral therapy at Chikankata Mission Hospital. Data collected were processed and analysed using Statistical Package for Social Science version 27. Univariate and backward multivariable logistic regression analysis was performed to identify factors associated with antiretroviral therapy defaulting. The level of significance was set at 5% with a confidence level of 95%. Results: Over half (58.4%) of the study participants defaulted on antiretroviral therapy. About 65.8% of study participants indicated improved health as the reason they defaulted on antiretroviral therapy. Most participants indicated that it was important to always go for antiretroviral therapy services (Adjusted Odds Ratio 1.95;95% Confidence Interval: [1.14 - 3.33], p = 0.015). Very few participants indicated poor family support for antiretroviral therapy services (Adjusted Odds Ratio 4.08;95% Confidence Interval: [2.02 - 8.23], p Conclusion: Defaulting on antiretroviral therapy continues to be a significant problem and needs to be addressed as a matter of priority. More counselling and awareness-raising programmes are required to improve knowledge and understanding on the importance of attending scheduled antiretroviral therapy clinics and services as well as the consequences of defaulting on antiretroviral therapy.

Correlation of human immunodeficiency virus and antiretroviral therapy with cardiac disorders

The occurrence of cardiovascular illness in the human immunodeficiency virus(HIV)community is increasing,with a particular focus on coronary heart disease.Patients infected with HIV have a higher risk of myocardial infarction compared to the general population in modern countries due to the development of effective antiretroviral medications and increased life expectancy.Those not receiving highly active antiretroviral therapy(ART)may experience common cardiac consequences,including myocarditis,dilated cardiomyopathy,endocarditis,pulmonary hypertension,pericardial effusion,and cardiotoxicity associated with non-antiretroviral drugs.After the use of highly active ART,continuing immune activation and systemic inflammation seem to play a central role in this process.Recent studies suggest that protease inhibitors might negatively impact the progression of HIV-related heart failure(HF),which complicates the determination of the best therapy strategy for HIVassociated cardiomyopathy.The objective of this review is to examine the pathophysiology and correlation of various antiretroviral drugs leading to HIV-associated HF.Additionally,we explore the causes of HIV-associated atherosclerotic cardiovascular disease,including the high frequency of classic cardiovascular risk factors in HIVinfected patients,as well as HIV-related factors like the use of ART and chronic inflammation despite successful treatment of HIV infection.Numerous studies have revealed that individuals living with HIV/acquired immune deficiency syndrome frequently experience HF.In conclusion,despite advancements in HIV care,HIV-infected individuals continue to face an increased risk of HIV-associated cardiomyopathy and atherosclerosis.Further research is necessary to comprehend the underlying causes and develop effective treatments for cardiovascular disease in this population.We also discuss the currently available therapeutic options and ongoing research to mitigate the risk of cardiovascular disease and inflammation in HIV-infected individuals.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province,China,2014–2020

Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

Glucose metabolism continuous deteriorating in male patients with human immunodeficiency virus accepted antiretroviral therapy for 156 weeks

BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH)who accepted primary treatment with the efavirenz(EFV)plus lamivudine(3TC)plus tenofovir(TDF)(EFV+3TC+TDF)regimen are unclear and warrant investigation.AIM To study the long-term dynamic characteristics of glucose metabolism and its contributing factors in male PLWH who accepted primary treatment with the EFV+3TC+TDF regimen for 156 wk.METHODS This study was designed using a follow-up design.Sixty-one male treatmentnaive PLWH,including 50 cases with normal glucose tolerance and 11 cases with prediabetes,were treated with the EFV+3TC+TDF regimen for 156 wk.The glucose metabolism dynamic characteristics,the main risk factors and the differences among the three CD4+count groups were analyzed.RESULTS In treatment-naive male PLWH,regardless of whether glucose metabolism disorder was present at baseline,who accepted treatment with the EFV+3TC+TDF regimen for 156 wk,a continuous increase in the fasting plasma glucose(FPG)level,the rate of impaired fasting glucose(IFG)and the glycosylated hemoglobin(HbA1c)level were found.These changes were not due to insulin resistance but rather to significantly reduced isletβcell function,according to the homeostasis model assessment ofβcell function(HOMA-β).Moreover,the lower the baseline CD4+T-cell count was,the higher the FPG level and the lower the HOMA-βvalue.Furthermore,the main risk factors for the FPG levels were the CD3+CD8+cell count and viral load(VL),and the factors contributing to the HOMA-βvalues were the alanine aminotransferase level,VL and CD3+CD8+cell count.CONCLUSION These findings provide guidance to clinicians who are monitoring FPG levels closely and are concerned about IFG and decreased isletβcell function during antiretroviral therapy with the EFV+3TC+TDF regimen for long-term application.

To explore patients’ perceptions about motivators and barriers of adherence to highly active antiretroviral therapy among people living with HIV: A qualitative study

Objective:For people living with HIV(PLHIV),strict adherence to highly active antiretroviral therapy(HAART)is the key to effective treatment and retention in human immunodeficiency virus(HIV)care.There are many factors which promote or halt the antiretroviral therapy(ART)adherence practices.Therefore,the present study aimed to examine the HAART adherence levels and to explore patients’views about barriers and facilitators to HIV treatment adherence.Methods:Semi-structured interviews were conducted among 15 PLHIV at the ART clinic of Dr.Ram Manohar Lohia Hospital,New Delhi.Interviews were audio-recorded in the local Hindi language,and bilingual experts(English and Hindi)transcribed verbatim.Qualitative data were coded for themes and subthemes and analyzed using a phenomenological approach as per thematic content analysis.Results:Feeling of hopelessness,delayed ART initiation,difficult initial phase of ART,forget to take ART on time,fear of disclosure of HIV diagnosis,lack of privacy and negative social support,and impact of lockdown due to COVID-19 were revealed as significant barriers to ART adherence.At the same time,commitment to raise and educate children,ART to increase life span,maintain oneself to be physically fit and healthy,only a single pill per day,very supportive counselors and health-care professionals,and hope to give birth to a healthy child were identified as facilitators of HIV retention.Conclusion:Understanding patient’s perception about ART adherence,its motivational and barrier factors which are directly affecting ART adherence and retention of PLHIV in HIV treatment and follow-ups are of utmost importance to improve ART adherence during HIV patient care services.

Survival of Antiretroviral Therapy Patients at the Outpatient Treatment Centre of the Community University Hospital of Bangui from 2015 to 2020

Background: The advent of antiretroviral treatment has considerably increased the life expectancy of people living with HIV in recent years. The Central African Republic, despite challenges related to the socio-political context, is committed to achieving the UNAIDS 90-90-90 targets and to the elimination of AIDS by 2030 advocated by the WHO. Objective: To analyze survival among HIV-positive adult patients on antiretroviral therapy from 2015 to 2020. Methods: This was a history-based cohort study of patients started on ART. The main variable was survival. The Kaplan-Meier method was used to describe the survival curve since inclusion in the cohort and a multivariate Cox model was used to investigate factors associated with mortality on ART. Results: A total of 145 naive patients started ART at the Outpatient Treatment Centre (OTC) in 2015. A female predominance was observed in our study with 78.08% of cases. The analysis of the patients’ fate at the time of point of treatment showed that 58.62% of them were still in active care and 13.10% died. The probability of survival at 5 years was 0.82 and mortality was significantly associated with very advanced disease (WHO stage IV) (p = 0.047) and anemia (p = 0.039). Conclusion: The majority of patients were still in care at the endpoint and mortality was significantly related to advanced disease and anemia. Early management of people living with HIV combined with better quality of care would improve their survival.

Insulin Sensitivity of Term Newborns Exposed in Utero to HIV and Antiretrovirals in Yaoundé

Introduction: Antiretrovirals (ARVs) and the human immunodeficiency virus (HIV) are implicated in the onset of insulin resistance. They cross the placental barrier thereby inducing early modifications of the fetal environment. The aim of our study was to assess insulin sensitivity in full-term newborns exposed in utero to HIV and ARVs in Yaoundé. Materials and Methods: We conducted an analytical cross-sectional study in 2 maternities in the city of Yaoundé from November 2021 to June 2022. We generated two groups of newborns (NBs): one group born to HIV positive mothers on ARVs and the other control group born to HIV negative mothers. Clinical data from mothers and NBs were collected. A homeostatic model assessment of insulin resistance (HOMA-IR) like index with C peptide served to assess insulin sensitivity. We used the Spearman correlation to measure the strength of association between insulin sensitivity and the different variables. A p-value Results: Of 70 neonates included, 35 were born to HIV positive mothers on ARVs and 35 to HIV negative mothers. The median age of HIV positive and negative mothers was 30 (27 - 32) and 34 (24 - 47) years, respectively (p = 0.791). The body mass index before pregnancy as well as the average newborn weights were comparable in both groups. The ARV protocol associating Tenofovir, Lamivudine, Efavirenz was used by 97.1% of HIV positive mothers. In the exposed NBs group, C peptide was significantly lower (p < 0.001) and blood glucose significantly higher (p < 0.001). The median values of HOMA-IR were 1.4 (0.8 - 1.9) and 2 (1.4 - 2.6) (p = 0.001) for exposed and unexposed NBs, respectively. Conclusion: Newborns exposed to HIV and ARVs had lower C peptide levels and were more sensitive to insulin. Close metabolic monitoring of these newborns would allow early diagnosis and management of any glucose regulation disorder.

The Effect Evaluation of Highly Active Antiretroviral Therapy to Patients with AIDS in Hubei Province of China

The effects of highly active antiretroviral therapy （HAART） to patients with AIDS in Hubei province of China were investigated in order to provide scientific evidence to reinforce the management of HAART. Self-made questionnaires and descriptive method of epidemiology were used to collect and describe the changes of clinical symptoms, HIV RIgA concentration, and immune function of patients with AIDS. After HAART, the effective rate of fever, cough, diarrhea, lymphadenectasis, weight loss, tetter, debility and fimgous infection was 92.4%, 90.85%, 92.91%, 90.73%, 93.69%, 89.04%, 92.34%, and 83.1%, respectively. Of 117 patients with detected HIV RNA concentration, 41.03% had declined over 0.5 log, and 52.99% less than 0.5 log. CD4^＋T cell count was obviously increased： the average number after HAART for 3 or 6 months was 237μL （26-755μL） and 239μL （17-833μL）, respectively HAART can improve AIDS patients＇ clinical symptoms, reduce HIV RNA concentration, and maintain immune function. It is very important for the effectiveness of HAART to raise clinical adherence of pa- tients with AIDS and have a persistent surveillance.

Development of an HPLC–UV assay method for the simultaneous quantification of nine antiretroviral agents in the plasma of HIV-infected patients

A new method using high-performance liquid chromatography coupled with ultra violet detection(HPLC–UV)was developed and validated for the simultaneous quantification of atazanavir,dolutegravir,darunavir,efavirenz,etravirine lopinavir,raltegravir,rilpivirine and tipranavir in human plasma.For the first time we reported here the development and validation of an HPLC–UV assay to quantify the frequently administered 9antiretroviral compounds including dolutegravir and rilpivirine.A simple solid phase extraction procedure was applied to 500 μL aliquots of plasma.The chromatographic separation of the drugs and internal standard(quinoxaline) was achieved with a gradient of acetonitrile and sodium acetate buffer on a C_(18) reverse-phase analytical column with a 25 min analytical run time.Calibration curves were optimised according to the therapeutic range of drug concentrations in patients,and the coefficient of determination(r^2) was higher than0.99 for all analytes.Mean intraday and interday precisions(RSD) for all compounds were less than 15.0%,and the mean accuracy(% deviation from nominal concentration) was also found to be less than 15.0%.Extraction recovery range was between 80% and 120% for all drugs analysed.The solid phase extraction and HPLC–UV method enable a specific,sensitive,and reliable simultaneous determination of nine antiretroviral agents in plasma.Good extraction efficiency and low limit of HPLC–UV quantification make this method suitable for use in clinical trials and therapeutic drug monitoring.

Self reported adherence to antiretroviral treatment and correlates in Hunan province,the Peoples Republic of China

Aims:This study aimed to describe the adherence level to antiretroviral therapy and its associated factors among people living with HIV in Hunan province,China.Methods:Across-sectional survey study was done at two major HIV treatment sites within Hunan province in China from July 2011 to Oct 2012 through face-to-face interviews.Adherence measures were captured using a 30-day visual analog scale(VAS).Results:A total of 418 participants consented and completed the questionnaires with the mean age being 38 years old.Based on VAS,28%of the participants had lower than 90%ART adherence level.The main reasons for missing drugs were;forgetting,being away from home,being busy and feeling worse after taking drugs.Logistic regression results showed that drug use(B=0.68,OR=2.11),time on ART(B=0.31,OR=0.72)and side effects(B=0.64,OR=1.82)were significantly associated with adherence to ART.Conclusion:Patients on ARVs in Hunan province are faced with adherence challenges notably drug abuse,drug regime scheduling challenges at the initial stages of therapy and drug side effects.It is therefore necessary to institute specific adherence interventions that target those who abuse drugs,ART naïve patients,and those experiencing side effects in order to achieve optimal ART adherence.

Effects of Antiretroviral Therapy and HIV Exposure in Utero on Adverse Pregnancy and Infant Outcomes:A Prospective Cohort Study in Guangzhou, China

Objective This study aimed to evaluate the effects of in-utero exposure to HIV and ART on pregnancy outcome and early growth of children.Methods This cohort study enrolled 802 HIV-infected pregnant women between October 2009 and May 2018 in Guangzhou, China. The women were assigned to receive combination ART(c ART) or mono/dual ART or no treatment. The primary outcomes were the combined endpoints of any adverse pregnancy outcome [including ectopic pregnancy, spontaneous abortion, stillbirth, preterm birth, small for gestational age(SGA)] and adverse early growth outcome(including infant death, HIV infection of mother-to-child transmission, and underweight, wasting and stunting of infants at 4 weeks of age).Results Adverse pregnancy outcomes occurred in 202(35.1%) of all enrolled HIV-infected women, and121(31.3%) of all infants exhibited adverse effects on early growth at 4 weeks of age. The rates of adverse pregnancy outcomes, spontaneous abortion, ectopic pregnancy, stillbirth, infant death and perinatal HIV infection were higher among women not receiving ART, compared to those treated with c ART or mono/dual ART(P < 0.05). However, women treated with c ART had a higher rate of SGA,compared to untreated women(P < 0.05). No differences in early infant growth were observed among the different treatment regimens.Conclusion Our findings underscore the essentiality of prioritizing HIV-positive pregnant women for ART, as even mono/dual ART available in resource-limited countries could improve pregnancy outcomes and infant survival.

Ocular manifestation and their associated factors among HIV/AIDS patients receiving highly active antiretroviral therapy in Southern Ethiopia

AIM：To assess the pattern of ocular manifestation and associated factors among human immunodeficiency virus（HIV）/acquired immunodeficiency syndrome（AIDS） patients on highly active antiretroviral therapy（HAART） at Hawassa University Referral Hospital, Southern Ethiopia. METHODS：A cross sectional study was conducted from January 2014 to April 2015. After obtaining informed written consent, 240 adult HIV/AIDS patients on HAART were randomly selected regardless of their ophthalmic symptoms, WHO status or CD4 count. Data were collected using structured questionnaires and ophthalmologic clinical examination. Data were entered and analyzed using SPSS version 20.0 software. RESULTS：The mean duration of HAART was 62.5mo. The prevalence of HIV related ocular manifestation was 14.2%. Seborrheic blepharitis（5%） was the most common ocular manifestation, followed by squamoid conjunctival growth（3.8%）. The rate of ocular manifestation was significantly higher among study participants who had CD4＋ count 〈200 cells/μL（AOR=3.83; 95%CI：1.315-11.153）, low duration of HAART（AOR=3.0; 95%CI：1.305-6.891） and who had primary school education [odds ratio（OR） =2.8; 95%CI：1.105-7.099]. Prevalence of visual impairment and blindness was 10.9% and 5.8%, respectively.CONCLUSION：HAART may be the reason for the decline in the prevalence of ocular manifestation in HIV/AIDS patients in the study area. Ophthalmologic screening of HIV/AIDS patients, especially those with CD4 counts of 〈200/μL cells and in the first five years of HAART followup is recommended to reduce visual impairment and/or blindness.

T-CELL RESPONSE OF ADVANCED AIDS PATIENTS AFTER HIGHLY ACTIVE ANTIRETROVIRAL THERAPY

Objective To investigate the response on late stage Chinese AIDS patients after highly active antiretroviral therapy （HAART）. Methods From October 2002 to March 2004, 20 cases of late stage Chinese AIDS patients were selected to participate in this opened and randomised study, we purposely chose those with CD4＋ T cell counts 〈 100/mm^3. All of them had one or two opportunistic infections and none had been treated with anti-HIV drugs. All patients were tested with CD4＋ （naive CD4＋ T cell defined by CD45RA＋ and CD62L＋, memory CD4＋ T cell defined by CD45RA-）, CD8＋ T cell, plasma HIV viral load, and clinical manifestations on before, during, and after HAART （5 different regimes） on 1, 3, 6, 9, and 12 months. Before HAART mean CD4＋ T cell counts were 32 ± 31 （range 2-91）/mm^3, and plasma HIV viral load were 5.07 ± 0.85（range 2.04-5.70） log copies/mL. In 1 month＇s time patients treated with HAAT had mean CD4＋ and CD8＋ T cell counts increasing rapidly. After 1 month the increasing speed turned to slow down, but HIV viral load decreased predominantly within the first 3 months. The major part of increasing CD4＋ T cells were memory CD4＋ T cells, as for naive CD4＋ T cells increasing low and slow. Clinical symptoms and signs improved, and opportunistic infections reduced. The quality of life will be far much better than before. Each patient was followed for 12 months, and had finished 12 months＇ HAAT. Conclusion This is the first report in China that late stage Chinese AIDS patients after HAART could have their immune reconstitution. The regular pattern is similar to what had been reported in Western countries and also in China. So it is worth to treat late stage Chinese AIDS patients with HAAT.

Graves’ Disease as a Late Manifestation of Immune Reconstitution Syndrome after Highly Active Antiretroviral Therapy in an HIV-1 Infected Patient

Context: Highly active antiretroviral therapy (HAART) inhibits the HIV replication and consequently increases CD4 levels and decreases viral load. This immune system improvement can trigger various immunological phenomena, entity called Immune Reconstitution Syndrome (IRS). Graves’ disease is a late Immune Reconstitution consequence. Patient: We report the case of a 48 years old man with HIV infection who developed Graves’ disease three years after he was on effective HAART because of the Immune Reconstitution Syndrome. At presentation he had a very low CD4 T-cell count (17 cells/μL). When he started HAART he presented a lipodystrophy syndrome. HAART was changed because of the persistent low CD4-T cells count (less than 100 cell/μL). Afterwards serum lipid levels began to decrease and that was the first manifestation of Graves’ disease, which was diagnosed when CD4 T-cells increased up to 343 cell/μL. Our patient developed Graves’ disease 36 months after initiating effective HAART with protease inhibitors which was coincident with viral suppression and a rise of CD4 T cells. Conclusion: The most immunosuppressed patients with a CD4 T cell count less than 100 cells/μL are at greatest risk for the development of Immune Reconstitution Syndrome after HAART initiation. We conclude that clinicians will have to consider the importance of the early diagnosis of thyroid disease to bring an adequate treatment.

Highly active antiretroviral therapy dysregulates proliferation and differentiation of human pre-adipocytes

AIM To investigate the mechanism(s) by which potential effects of multi-drug highly-active antiretroviral therapy contributes to lipodystrophy syndrome. METHODS Preadipocytes from healthy donors were assessed for proliferation and differentiation in the presence of nucleoside reverse transcriptase inhibitors(NRTIs), nonnucleoside reverse transcriptase inhibitors(NNRTIs), and protease inhibitors(PIs) individually and in combination. Effects on proliferation were assessed with a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay and effects on differentiation were assessed from glycerol-3-phosphate dehydrogenase(GPDH) activity and quantitation of Oil Red O staining for intracellular lipid. Data were analyzed with a randomized block ANOVA with post-hoc Fisher's Least Significant Difference test. RESULTS Preadipocyte proliferation was inhibited by a combination of NNRTI + NRTI(14% at 48 h, P < 0.001) and PI + NRTI(19% at 48 h, P < 0.001) with additional suppression when ritonavir(RTV) was added(26% at 48 h). The drug combination of atazanavir(ATV) + RTV + emtricitabine(FTC) + tenofovir(TDF) had the greatest inhibitory effect on proliferation at 48 h. Preadipocyte differentiation was most significantly reduced by the efavirenz + FTC + TDF assessed either by GPDH activity(64%) or lipid accumulation(39%), P < 0.001. Combining NRTIs with a PI(ATV + FTC + TDF) significantly suppressed differentiation(GPDH activity reduced 29%, lipid accumulation reduced by 19%, P < 0.01). This effect was slightly greater when a boosting amount of RTV was added(ATV + FTC + TDF + RTV, P < 0.001). CONCLUSION Although combination antiretroviral therapy is clinically more efficacious than single drug regimens, it also has a much greater inhibitory effect on preadipocyte proliferation and differentiation.

Effects of viremia and CD4 recovery on gut“microbiome-immunity”axis in treatment-na?ve HIV-1-infected patients undergoing antiretroviral therapy

BACKGROUND Human immunodeficiency virus type 1(HIV-1)infection is characterized by persistent systemic inflammation and immune activation,even in patients receiving effective antiretroviral therapy(ART).Converging data from many cross-sectional studies suggest that gut microbiota(GM)changes can occur throughout including human immunodeficiency virus(HIV)infection,treated by ART;however,the results are contrasting.For the first time,we compared the fecal microbial composition,serum and fecal microbial metabolites,and serum cytokine profile of treatment-na?ve patients before starting ART and after reaching virological suppression,after 24 wk of ART therapy.In addition,we compared the microbiota composition,microbial metabolites,and cytokine profile of patients with CD4/CD8 ratio<1(immunological non-responders[INRs])and CD4/CD8>1(immunological responders[IRs]),after 24 wk of ART therapy.AIM To compare for the first time the fecal microbial composition,serum and fecal microbial metabolites,and serum cytokine profile of treatment-na?ve patients before starting ART and after reaching virological suppression(HIV RNA<50 copies/m L)after 24 wk of ART.METHODS We enrolled 12 treatment-na?ve HIV-infected patients receiving ART(mainly based on integrase inhibitors).Fecal microbiota composition was assessed through next generation sequencing.In addition,a comprehensive analysis of a blood broad-spectrum cytokine panel was performed through a multiplex approach.At the same time,serum free fatty acid(FFA)and fecal short chain fatty acid levels were obtained through gas chromatography-mass spectrometry.RESULTS We first compared microbiota signatures,FFA levels,and cytokine profile before starting ART and after reaching virological suppression.Modest alterations were observed in microbiota composition,in particular in the viral suppression condition,we detected an increase of Ruminococcus and Succinivibrio and a decrease of Intestinibacter.Moreover,in the same condition,we also observed augmented levels of serum propionic and butyric acids.Contemporarily,a reduction of serum IP-10 and an increase of IL-8 levels were detected in the viral suppression condition.In addition,the same components were compared between IRs and INRs.Concerning the microflora population,we detected a reduction of Faecalibacterium and an increase of Alistipes in INRs.Simultaneously,fecal isobutyric,isovaleric,and 2-methylbutyric acids were also increased in INRs.CONCLUSION Our results provided an additional perspective about the impact of HIV infection,ART,and immune recovery on the"microbiome-immunity axis"at the metabolism level.These factors can act as indicators of the active processes occurring in the gastrointestinal tract.Individuals with HIV-1 infection,before ART and after reaching virological suppression with 24 wk of ART,displayed a microbiota with unchanged overall bacterial diversity;moreover,their systemic inflammatory status seems not to be completely restored.In addition,we confirmed the role of the GM metabolites in immune reconstitution.

Identifications of drug resistance mutations among antiretroviral treatment naive HIV-1 patients in Peninsular Malaysia

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 A71 V and L10 l 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.