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.

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.

Elevated homocysteine levels in human immunodeficiency virus-infected patients under antiretroviral therapy: A meta-analysis

AIM: To evaluate the association between the levels of homocysteine(Hcy), folate, vitamin B12 in human immunodeficiency virus(HIV)-infected patients who were treated with antiretroviral therapy(ART) or not treated with ART.METHODS: The Pub Med and Scielo databases were searched. Eligible studies regarding plasma Hcy level in HIV-infected patients were firstly identified. After careful analysis by two independent researches, the identified articles were included in the review according to two outcomes(1) Hcy, folate and vitamin B12 blood concentration in HIV-infected subjects vs health controls and;(2) Hcy blood concentration in HIV-infected subjects under ART vs not treated with ART. RevM an(version 5.2) was employed for data synthesis.RESULTS: A total of 12 studies were included in outcome 1(1649 participants, 932 cases and 717 controls). Outcome 1 meta-analysis demonstrated higher plasma Hcy(2.05 μmol/L; 95% CI: 0.10 to 4.00, P < 0.01) and decreased plasma folate concentrations(-2.74 ng/m L; 95%CI:-5.18 to-0.29, P < 0.01) in HIV-infected patients compared to healthy controls. No changes in vitamin B12 plasma concentration were observed between groups. All studies included in the outcome 2 meta-analysis(1167 participants; 404 HIVinfected exposed to ART and 757 HIV-infected non-ART patients) demonstrated higher mean Hcy concentration in subjects HIV-infected under ART compared to nonART HIV subjects(4.13 μmol/L; 95%CI: 1.34 to 6.92, P < 0.01).CONCLUSION: This meta-analysis demonstrated that the levels of Hcy and folate, but not vitamin B12, were associated with HIV infection. In addition, Hcy levels were higher in HIV-infected patients who were under ART compared to HIV-infected patients who were not exposed to ART. Our results suggest that hyperhomocysteinemia should be included among the several important metabolic disturbances that are associated with ART in patients with HIV infection.

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.

Competing Risk Model for Time to Development of Tuberculosis among Adults on Combination Antiretroviral Treatment

The purpose of this study was to identify factors affecting the time to development of tuberculosis in the presence of competing risks. In this case death before developing tuberculosis was deemed a competing risk because it altered the occurrence of the outcome of interest being time to development of tuberculosis from baseline. We used data from a randomized longitudinal clinical trial study called the “Tshepo” study. The “Tshepo” study was a 3-year randomized clinical study following 650 ART-naïve adults (69.4% female) from Botswana who initiated first-line NNRTI-based ART. Participants were assigned in equal proportions (in an open-label, unblinded fashion) to one of 6 initial treatment arms and one of two adherence arms using permuted block randomization. Randomization was stratified by CD4+ cell count (less than 200 cells/mm3, 201 - 350 cells/mm3) and by whether the participants had an adherence assistant. Classical methods such as the Kaplan-Meier method and standard Cox proportional hazards regression were used to analyze survival data ignoring the competing event(s) which may have been inappropriate in the presence of competing risks. The idea was to use competing risk models to investigate how different treatment regimens affect the time to the development of TB and compare the results to those obtained using the classical survival analysis model which does not account for competing risks. Amongst 38 patients who died 15.8% of them developed tuberculosis whilst 84.2% of those who died did not develop the outcome of interest. The hazard ratio of treatment C was 1.069 implying that the risk of developing TB in patients taking treatment C is about 6.9% higher compared to those taking treatment A having adjusted for baseline age, baseline BMI, baseline CD4, Hemoglobin and gender. Similarly, after accounting for competing risks the hazard ratio for treatment C was about 1.89 implying that the risk of developing TB amongst those taking treatment C was about 89% higher as compared to those taking treatment A. From the obtained results it was thus concluded that the standard Cox model of time to event data in the presence of competing risks underestimated the hazard ratios hence when dealing with data with multiple failure events it is important to account for competing events.

One-Year Outcomes of Women Started on Antiretroviral Therapy during Pregnancy before and after the Implementation of Option B+ in Malawi: A Retrospective Chart Review from Three Facilities

Objective: To compare one-year outcomes of women started on antiretroviral therapy (ART) during?pregnancy in the pre-Option B+ era to those in the Option B+ era. Methods: A retrospective chart review was performed at three sites in Malawi. Women were included in the “pre-Option B+” cohort if they started ART during pregnancy for a CD4 count 3?or WHO 3/4 condition and in the “Option B+” cohort if they started ART during pregnancy regardless of CD4 count or clinical stage. One-year outcomes were compared using Fisher’s exact and ANOVA F-tests. Results: A higher proportion of women in the pre-Option B+ cohort started ART at WHO stage 3/4 (11.9% versus 1.1%, P < 0.001), switched ART regimens (5.9% versus 0%, P = 0.002), or died in the first year after starting treatment (3.9% versus 0.5%, P = 0.05). While more women in the Option B+ cohort had poor adherence or defaulted, these differences were not significant. Conclusions: At our study sites, the transition to Option B+ has been associated with ART initiation in women with less advanced HIV infection, improved medication tolerability, and lower mortality. Further research is needed to better understand outcomes of Option B+.

Mortality of HIV-Infected Patients on Antiretroviral Therapy in a Large Public Cohort in West Africa, Burkina Faso: Frequency and Associated Factors

Background: In sub Saharan Africa, small size surveys have demonstrated early high mortality among infected patients on antiretroviral therapies (ART). Few studies have been conducted in large cohorts of HIV-patients in public health care system in West Africa. Objectives: Our study aims to determine mortality rate and its predictors in a cohort of patients on ART in a public daycare hospital in Burkina Faso. Methods: We have carried out a retrospective cohort study. All HIV-infected patients on ART between January 1st 2008 and December 31st 2011 were included in the study. Survival probability was estimated by the Kaplan-Meier method. Cox regression analysis was used to identify associated factors to mortality. Results: A total of 2243 HIV-infected patients were included in the study. During the follow-up, 218 patients representing 9.7% were lost. About 104 patients representing 4.6% were transferred and 1691 representing 75.4% were still in the therapeutic cohort. There were 230 death cases for a total of 4282 persons-years, (5.4 deaths for 100 persons-years;95% CI: 4.8 -6.3). The survival probabilities after 6 months, 1 year and 2 years were 92.6%, 91% and 88.9% respectively. For the multivariate analysis, the following factors were independently associated to death: male gender, BMI .5 kg/m2, WHO stage 3 and 4, HIV-2, T-CD4 lymphocytes < 200/μl, haemoglobin rate g/dl and creatinine clearance 2. Conclusions: Our study provides for the first time mortality rates and its predictors among HIV-patients on antiretroviral treatment in a large cohort in public health sector in Burkina Faso. It highlights the importance of early HIV screening to limit ART initiation at advanced HIV infection stages.

Additional attention to combination antiretroviral therapy-related lipodystrophy

The occurrence of lipodystrophy in patients taking antihuman immunodeficiency virus(HIV) medications is a serious problem as it is irreversible even after drug withdrawal. Although it was first recognized in patients taking proteinase inhibitors, other types of anti-HIV agents can also cause lipodystrophy. In a recent publication by Jones et al entitled "Highly active antiretroviral therapy dysregulates proliferation and differentiation of human pre-adipocytes" in World Journal of Virology, it was reported that simultaneous treatment of human subcutaneous adipocytes with anti-HIV drugs with different mechanisms of action synergistically exerted antiadipogenesis effects in vitro, warning us to take utmost care in every case receiving combination antiretroviral therapy(cART). For elucidation of the molecular basis for cART-related lipodystrophy, multi-faceted approaches should be taken, based on a deeper understanding of the development and organization of adipose tissues.