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.

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.

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.

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 particip-ate in this opened and randomised study, we purposely chose those with CD4+ T cell counts < 100/mm3. 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. Results Before HAART mean CD4+ T cell counts were 32 ± 31(range 2-91)/mm3, 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 HAART 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’ HAART. 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 HAART.

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.

Activation and coreceptor expression of T lymphocytes induced by highly active antiretroviral therapy in Chinese HIV/AIDS patients

Background At the end of 2005, 650 000 people lived with human immunodeficiency virus type-1 （HIV-1） in China, of whom 75 000 were AIDS patients. Many AIDS patients received highly active antiretroviral therapy （HAART） supported by the ＂China CARES＂ program but the immune responses of HAART were seldom reported. This study investigated the effect of HAART on the activation and coreceptor expression of T lymphocytes in Chinese HIV/AIDS patients and evaluated its effect on immune reconstitution. Methods Seventeen HIV/AIDS patients were enrolled and three-color-flow cytometry was used to detect the activation of HLA-DR CD38 and the coreceptor CCR5, CXCR4 expression on T lymphocytes in whole blood samples taken from the patients before and after 3- or 6-month HAART. Results The activation percents of CD4^＋, CD8^＋ T lymphocytes were significantly higher before therapy than the normal controls （HLA-DR/CD4： 40.47±18.85 vs 11.54±4.10; CD38/CD4： 81.34± 10.86 vs 53.34± 11.44; HLA-DR/CD8：63.94±12.71 vs 25.67±9.18; CD38/CD8： 86.56± 11.41 vs 58.84±6.16,. all P〈0.01）. After 6-month combined antiretroviral treatment, the activation of T lymphocytes in HIV/AIDS patients was significantly decreased （HLA-DR/CD4：28.31± 13.48; CD38/CD4：69.88 ± 12.64; HLA-DR/CD8： 46.56± 18.64; CD38/CD8： 70.17±14.54, all P〈0.01 compared with the pre-treatment values）. Before the treatment, CCR5 expression on CD8^＋ T lymphocytes was up-regulated while CXCR4 expression on CD8^＋ T lymphocytes downregulated in HIV/AIDS patients compared with the normal controls （CD8/CCR5：70.91 ± 10.03 vs 52.70± 7.68; CD8/CXCR4：24.14±11.08 vs 50.05±11.68, all P〈0.01）. After 6-month HAART, CCR5 expression on CD8^＋ T lymphocytes significantly decreased （56.35±2.96, P〈0.01）, while CXCR4 expression on CD8^＋ T lymphocytes increased （36.95±9.96, P〈0.05） compared with the pre-treatment and the normal controls. A significant statistical relationship was observed between the expression of activation markers, CCR5 and the CD4^＋ T lymphocyte counts after HAART （P〈0.05）. Conclusions Reduced activation of T lymphocytes and a normalization of coreceptor expression were observed in Chinese HIV/AIDS patients after HAART. Immunity can be restored in HIV/AIDS patients receiving HAART.

Clinical outcomes and immune reconstitution in 103 advanced AIDS patients undergoing 12-month highly active antiretroviral therapy

Background Highly active antiretroviral therapy （HAART） produces profound suppression of HIV replication, substantial increase in CD4^＋ T cells, and partial reconstitution of the immune system. However, the numbers of subjects were small in previous Chinese studies. This study evaluated the efficacy and side effects of HAART in Chinese advanced AIDS patients.Methods One hundred and three antiretroviral drug naive AIDS patients were enrolled in this study and were divided into two groups by their baseline CD4^＋ count： 〈 100 cells/μl or ≥ 100 cells/μl. Clinical, virological and immunological outcomes were monitored at baseline and at 1, 3, 6, 9 and 12 months during the course of treatment with HAART.Results One patient died and another was lost from the follow-up. For the remaining 101 HIV/AIDS patients at the 12th month during the HAART, the plasma viral load （VL） was reduced to （3.2±0.7） lg copies/ml, the CD4^＋ count increased to （168 ±51） cells/μl [among which the naive phenotype （CD45RA^＋CD62L^＋） increased to （49 ±27） cells/μl and the memory phenotype （CD45RA^-） increased to （119 ±55） cells/μl], and the percentage of CD4^＋CD28^＋ cells increased. At the same time, there was a significant reduction of CD8^＋ T cell activation. In the 69 patients with the baseline CD4^＋ count 〈100 cells/μl, 37 had a VL 〈50 copies/ml; while in the 34 patients with the baseline CD4^＋ count ≥ 100 cells/μl, 25 had a VL 〈50 copies/ml, the difference between the two groups was statistically significant. The CD4^＋ T cell count showed a two-phase increase during HAART and a significant positive correlation was shown between the change of CD4^＋ count and plasma VL. Over 12 months of HAART, 10 patients had gastrointestinal side effects, 13 peripheral neuritis, 7 hepatic lesions, 8 hematological side effects, 8 skin rashes, 10 lipodystrophy and 1 renal calculus.Conclusions Immune reconstitution as well as the significantly improved clinical outcomes is observed in Chinese advanced AIDS patients after HAART. Side effects are common during HAART and require clinical attention.

Cytomegalovirus retinitis in the highly active anti-retroviral therapy era

Cytomegalovirus(CMV)retinitis is an opportunistic infection that has traditionally affected those who have HIV/AIDS or immunosuppressed individuals.CMV retinitis previously infected one-third of AIDS patients in the pre-highly active antiretroviral therapy(HAART)era,but since HAART,Western countries have seen an 80%decrease in the incidence of the disease.More recently,CMV retinitis has been reported in patients who are immunosuppressed,often due to chemotherapy or immunomodulatory medications.The diagnosis of CMV retinitis is often suspected based on clinical findings,with polymerase chain reaction for confirmation of CMV,especially in atypical cases.Highly active antiretroviral therapy and anti-CMV medications(systemic or local)remain the mainstay of treatment.However,for those who are not responsive to HAART,CMV retinitis remains a challenge,and can still lead to significant vision loss.Moreover,a regimen of anti-CMV medications can sometimes lead to viral resistance or organ toxicity.Complications such as immune recovery retinitis and rhegmatogenous retinal detachments continue to threaten the vision of patients who develop CMV retinitis.These complications can arise following initiation of treatment or if patients show disease progression.Proper vision screening for CMV retinitis in immunosuppressed patients at-risk is necessary for early detection and treatment.

A one-year clinical trial using didanosine, stavudine and nevirapine for highly active antiretroviral therapy

Antiretroviral therapy is a key determinant in the treatment and prevention of human immunodeficiency virus (HIV) infection. Initial treatment for patients with HIV infection generally includes two nucleoside reverse transcriptase inhibitors (NRTI) and a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI). The combination antiretroviral therapy (refers to highly active antiretroviral therapy or HAART) showed a significant effect upon reducing morbidity and mortality of HIV disease. Cao and colleagues^1 began the clinical application of HAART in 1999 and completed the first clinical trial in China using a combination of two NRTIs and one PI. The result in using combivir (AZT+3TC) and indinavir (2 NRTIs+1 PI) are consistent with those reported in the literature.~2 In this study, we report the first virological and immunological outcomes in HIV infected Chinese patients treated with a combination of didanosine, stavudine and nevirapine (2 NRTIs+1 NNRTI) for 52 weeks.

Impact of baseline CD4^＋ T cell counts on the efficacy of nevirapinebased highly active antiretroviral therapy in Chinese HIV/AIDS patients： a prospective, multicentric study

Background CD4^＋T cell counts have been used as the indicator of human immunodeficiency virus type 1 （HIV-1） disease progression and thereby to determine when to start highly active antiretroviral therapy （HAART）. Whether and how the baseline CD4^＋T cell count affects the immunological and viral responses or adverse reactions to nevirapine （NVP）-containing HAART in Chinese HIV-1 infected adults remain to be characterized. Methods One hundred and ninety-eight HIV-seropositive antiretroviral therapy （ART）-naive subjects were enrolled into a prospective study from 2005 to 2007. Data were analyzed by groups based on baseline CD4^＋T cell counts either between 100-200 cells/μl or 201-350 cells/μl. Viral responses, immunologic responses and adverse events were monitored at baseline and at weeks 4, 12, 24, 36, 52, 68, 84, 100. Results Eighty-six and 112 subjects ranged their CD4^＋T cell counts 100-200 cells/μl and 201-350 cells/μl, respectively. The pre-HAART viral load in CD4 201-350 cells/μl group was significantly lower than that in CD4 100-200 cells/μl group （P=0.000）. After treatment, no significant differences were observed between these two groups either in the plasma viral load （pVL） or in the viral response rate calculated as the percentage of pVL less than 50 copies/ml or less than 400 copies/ml. The CD4^＋T cell counts were statistically higher in the 201-350 group during the entire follow-ups （P 〈0.01） though CD4^＋ T cell count increases were similar in these two groups. After 100-week treatment, the median of CD4^＋ T cell counts were increased to 331 cells/μl for CD4 100-200 cells/μl group and to 462 cells/μl for CD4 201-350 cells/μl group. Only a slightly higher incidence of nausea was observed in CD4 201-350 cells/μl group （P=0.05） among all adverse reactions, including rash and liver function abnormality. Conclusions The pVLs and viral response rates are unlikely to be associated with the baseline CD4^＋T cell counts. Initiating HAART in Chinese HIV-1 infected patients with higher baseline CD4^＋T cell counts could result in higher total CD4^＋T cell counts thereby achieve a better immune recovery. These results support current guidelines to start HAART at a threshold of 350 cells/μl.

Autoimmune hepatitis in a patient infected by HIV-1 and under highly active antiretroviral treatment:Case report and literature review

Liver disease has recently been described as an important cause of morbidity and mortality in patients infected with human immunodeficiency virus(HIV). Liver test changes are useful surrogates of the burden of liver disease. Previous studies have shown that transaminase elevations are frequent among these patients. The cause of those changes is harder to establish in HIV-patients. We present a 61-year-old caucasian male,diagnosed with HIV type 1 infection since 1998,under highly active antiretroviral treatment(HAART),with virological suppression and immunological recovery. He presented in a follow-up laboratory workup high values of transaminases,arthralgia at the hip joints and hepatomegaly. Liver function tests were normal. The antibodies to hepatitis viruses were negative. However,autoimmune study and liver biopsy were compatible with autoimmune hepatitis(AIH). The AIH is a rare di-agnosis in HIV-infected patients perhaps because the elevation of transaminases and changes in liver function tests are often associated to HAART or to other possible liver diseases,namely viral hepatitis and non-alcoholic steatohepatitis. The diagnosis may be underestimated. There are no specific recommendations available for the treatment of HIV-associated AIH although the immunosupression with slower tapering seems the most reasonable approach.

Cutaneous Manifestations of HIV/AIDS in the Era of Highly Active Antiretroviral Therapy: Evidence from Bangladesh

Objective:Skin diseases are common and striking features of patients with human immunodeficiency virus/acquired immunodeficiency syndrome(HIV/AIDS)and may vary considerably by ethnic and geographic regions and by the influence of highly active antiretroviral therapy(HAART).However,little information exists regarding the cutaneous manifestations of patients with HIV/AIDS in Bangladesh.This study was performed to elucidate the spectrum of cutaneous disorders in patients with HIV/AIDS in the era of HAART.Materials:This descriptive cross-sectional study was carried out in Chittagong Medical College Hospital,Bangladesh from January 2017 and December 2020.Diagnosed case of HIV/AIDS for HAART therapy and all cases of HIV/AIDS who are already on HAART therapy were included in this study.Descriptive statistical analysis was carried out by using frequencies and percentages.Results:Of 40 patients with HIV/AIDS,22(55.0%)were male and 18(45.0%)were female.The patients ranged in age from 8 to 60 years,with a mean age of 38±0.966 years.Among all age groups,the highest 19(47.5%)patients were in the 31-to 40-year age group.Most of the patients were migrant workers[22/40(55.0%)]with low socioeconomic status[32/40(80.0%)],and the most common transmission mode was heterosexual activity[36/40(90.0%)].Most of the patients[32/40(80.0%)]had mucocutaneous disorders,30/40(75.0%)had infective dermatoses,and 21/40(52.5%)had non-infective inflammatory dermatoses.Eight of forty(20.0%)patients presented with three or more skin disorders.The most common infective dermatoses were fungal infections[15/40(37.5%)],followed by viral infections[8/40(20.0%)],bacterial infections[4/40(10.0%)],and scabies[3/40(7.5%)].The most common non-infective dermatosis was generalized pruritus[6/40(15.0%)],followed by prurigo simplex[4/40(10.0%)],psoriasis[4/40(10.0%)],eczema[3/40(7.5%)],pruritic papular eruption[1/40(2.5%)],seborrheic dermatitis[1/40(2.5%)],urticaria[1/40(2.5%)],and xerosis[1/40(2.5%)].Patients treated with HAART had decreased rates of oral candidiasis and herpes simplex but increased rates of drug reactions[19/40(47.5%)].The most common drug eruption following HAART was a morbilliform rash[11/40(27.5%)],and the most common offending agent was nevirapine.The prevalence of mucocutaneous disorders was higher in patients with a CD4 cell count of<200 cells/mm3.Conclusions:A wide range of mucocutaneous disorders is observed in Bangladeshi patients with HIV/AIDS,and HAART has an impact on the spectrum of HIV/AIDS-associated mucocutaneous disorders.Skin and mucocutaneous disorders are seen at every stage of HIV/AIDS and are the initial presentation in most patients in Bangladesh.There is a need for increased attention to the diagnosis and treatment of skin diseases affecting the quality of life of patients withHIV/AIDS.

Prevalence of liver injury among patients with acquired immunodeficiency syndrome treated with highly active antiretroviral therapy in China

OBJECTIVE: To estimate the prevalence of liver injury among patients with acquired immunodeficiency syndrome(AIDS) who received highly active antiretroviral therapy(HAART) in rural Henan Province in China, and to explore whether Traditional Chinese Medicine(TCM) treatment based on HAART would increase this risk.METHODS: This was a retrospective cross-sectional study. We collected medical information on patients with AIDS from two treatment databases in2014. Criteria established by the AIDS Clinical Trials Group in 1996 were used for grading liver injury,classified based on the limit of normal(ULN) for alanine transaminase and aspartate aminotransferase:grade 1(1.25-2.5 × ULN); grade 2(2.6-5 × ULN);grade 3(5.1-10 × ULN); and grade 4(> 10 × ULN).Factors associated with liver injury were evaluated using a logistic regression model.RESULTS: A total 6953 patients with AIDS(3324 male and 3629 female patients) were enrolled into this study. The prevalence of liver injury was 22.0%(18.0% grade 1, 3.1% grade 2, 0.9% grade 3). In multivariate analysis, patients aged 34-45 years were more likely to have liver injury than patients in other age groups [adjusted odds ratio(AOR), 1.39; 95%CI, 1.01-1.91)]. Other factors associated with liver injury included male sex(AOR, 1.64; 95% CI,1.46-1.85), HIV infection via blood(AOR, 1.47; 95%CI, 1.19-1.82), hepatitis B virus antibody positive(AOR, 1.07; 95% CI, 0.85-1.36), and hepatitis C virus(HCV) antibody positive(AOR, 2.76; 95% CI,2.28-3.34).CONCLUSION: The prevalence of liver injury was relatively high among HAART-experienced patients. Several factors associated with liver injury included male sex, age 35-45 years old, HIV infection through blood, and concurrent HCV infection. TCM had no relationship with liver injury in patients receiving HAART.

Longitudinal observation of an interferon gamma-released assay （T-SPOT.TB） for Mycobacterium tuberculosis infection in AIDS patients on highly active antiretroviral therapy

Background T-SPOT.TB is a novel test for tuberculosis infection with higher sensitivity and specificity than the traditional tuberculin skin test （TST）. However, there are no longitudinal data in the literature evaluating T-SPOT.TB for Mycobacterium tuberculosis in patients with acquired immune deficiency syndrome （AIDS） on highly active antiretroviral therapy （HAART）. The objective of this study was to assess the value of T-SPOT.TB longitudinally in AIDS patients on HAART without prophylaxis for tuberculosis.Methods A prospective observational study was conducted in 50 AIDS patients on HAART. None of the subjects had evidence of active tuberculosis. T-SPOT.TB, a T-cell-based interferon y released assay, was performed at the onset of the study and repeated 24 months thereafter. Subjects were evaluated every 6 months during the 36-month follow-up. Results Twenty-one （42%） AIDS patients on HAART tested positive by T-SPOT.TB （95% Cl 28.3%-55.7%）. The pooled spot-forming cells of early secretory antigenic target-6 （ESAT-6） and culture filtrate protein-10 （CFP-10） peptides were 68/million peripheral blood mononuclear cell （PBMC） （interquartile range 44-220）. The average number of CD4 cells in subjects was （305±152） cells/Ml and there was no significant difference in T-SPOT.TB response rates between subjects with CD4 cell counts 〈200 cells/ul （7/15 （46.7%）, 95% C/21.5%-71.9%） and those with CD4 cell counts≥200 cells/ul （14/35 （40.0%）, 95% Cl 23.8%-56.2%, P=0.662）. In the 32 subjects who completed the 24-month follow-up, 10 underwent T-SPOT.TB reversion, one had T-SPOT.TB conversion, six remained positive and 15 remained negative. None of them advanced to active tuberculosis during the 36-month follow-up.Conclusion The inactive status of tuberculosis infection may be maintained for a long period in AIDS patients on HAART.

Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs

For human immunodeficiency virus(HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy(HAART) representing a new perspective of life for these patients. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity, which led to a better and longer quality of life for HIV-1-infected patients. Apart from the substantial benefits that result from the use of various HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects related to metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis. New drugs are being studied, new therapeutic strategies are being implemented, and the use of statins, fibrates, and inhibitors of intestinal cholesterol absorption have been effective alternatives. Changes in diet and lifestyle have also shown satisfactory results.

Pharmacogenetics as a tool to tailor antiretroviral therapy: A review

Highly active antiretroviral therapy(HAART) has substantially changed human immunodeficiency virus(HIV) infection from an inexorably fatal condition into a chronic disease with a longer life expectancy. This means that HIV patients should receive antiretroviral drugs lifelong, and the problems concerning with a chronic treatment(tolerability, side effects, adherence to treatment) have now become dominant. In this context, strategies for the treatment personalization have taken a central role in optimizing the therapeutic response and prevention of adverse drug reactions. In this setting, the study of pharmacogenetics features could be a very useful tool in clinical practice; moreover, nowadays the study of genetic profiles allows optimizations in the therapeutic management of People Living With HIV(PLWH) through the use of test introduced into clinical practice and approved by international guidelines for the adverse effects prevention such as the genetic test HLA-B*5701 to detect hypersensitivity to Abacavir. For other tests further studies are needed: CYP2B6 516 G > T testing may be able to identify patients at higher risk of Central Nervous System side effects following standard dosing of Efavirenz, UGT1A1*28 testing before initiation of antiretroviral therapy containing Atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Pharmacogenetics represents a research area with great growth potential which may be useful to guide the rational use of antiretrovirals.

Highly active antiretroviral therapy per se decreased mortality and morbidity of advanced human immunodeficiency virus disease in Hong Kong

Background Morbidity and mortality of advanced human immunodeficiency virus infection （HIV） have declined in Western industrialized countries since the availability of highly active antiretroviral therapy （HAART）. It is unclear if this has also happened in Hong Kong. Methods We studied a retrospective cohort of patients with advanced HIV disease in Hong Kong, China. First, the mortality of advanced HIV disease per year was calculated for the decade 1993 to 2002, both annually and according to patient observation before and after 1997. Second, the event rates were estimated for the clinical end points of acquired immune deficiency syndrome （AIDS） and death. Univariate and multivariate analyses were then performed to identify associated factors. Results The crude mortality of advanced HIV disease declined from 10. 8 - 30. 4 per 100 patients during 1993 - 1996, to 0. 8 - 6. 9 per 100 patients during 1997 - 2002. A rate ratio of 4. 04 （95% CI, 2. 52 - 6. 47） was evident for those observed in 1993 - 1996, compared to those in 1997 - 2002. In a multivariate analysis where calendar period was adjusted, use of＇highly active antiretroviral therapy was associated with rate ratios of 0. 13 （95% CI, 0. 05 -0. 33） for death after AIDS, 0. 08 （95% CI, 0. 04 -0. 19） for AIDS after a CD4 cell count 〈200/μ1, and 0.21 （95% CI, 0.07 -0.67） for death after CD4 cell count 〈200/μl. In the same analysis, calendar period ceased to be a significant factor after adjustment for use of HAART. Conclusions The mortality and morbidity of advanced human immunodeficiency virus disease have declined in Hong Kong. This improved prognosis was attributable to the use of highly active antiretroviral therapy.

Effect of treatment course of comprehensive intervention with Traditional Chinese Medicine on mortality of acquired immunodeficiency syndrome patients treated with combined antiretroviral therapy

OBJECTIVE:To investigate the effect of a treatment course of comprehensive intervention with Traditional Chinese Medicine(TCM) on the mortality of patients with acquired immunodeficiency syndrome(AIDS) treated with combined antiretroviral therapy(c ART).METHODS:AIDS patients who had taken c ART in a national TCM human immunodeficiency virus treatment trial program(NTCMTP) before 2009 were enrolled in this study and followed for 36 months from November 2009.Patients enrolled in the NTCMTP in 2004 were taken as the first group,those enrolled in 2006 as the second group,and those enrolled in 2009 as the third group.Cumulative survival rates were calculated by the life table method.Survival curves for subgroups were compared by the log-rank test.Hazard ratios were calculated with a Cox proportional hazards model.RESULTS:A total of 1443 AIDS patients were followed for 3 years(4198 person-years).During this period,91(6.3%) patients died and 13(0.9%) were lost to follow-up.The total mortality rate was 2.17/100 person-years.The mortality rate of patients enrolled in the NTCMTP in 2004 was 1.49/100 person-years,which was lower than that of patients enrolled in 2006(2.23/100 person-years) and 2009(3.48/100 person-years).After adjusting for other factors,a shorter time of treatment with TCM,male sex,older age,lower CD4 + T-cell counts,and long-term treatment with c ART were risk factors of mortality.CONCLUSION:Long-term treatment with TCM decreased the mortality risk of AIDS patients.Factors such as being male,older age,CD4+ T-cell counts,and time of treatment with TCM and c ART were correlated with mortality.

Impact of body fat changes in mediating the effects of antiretroviral therapy on blood pressure in HIV-infected persons in a sub-Saharan African setting

Background:Previous studies of HIV-infected patients have shown significant associations between highly active antiretroviral therapy(HAART)and increased blood pressure;however,the mechanisms involved are less clear.Therefore,we sought to investigate the potential impact of body fat changes in mediating the effects of HAART on blood pressure changes among people living with HIV.Methods:Four hundred six consenting patients(≥18 years of age)attending a tertiary HIV clinic in semi-urban Nigeria were recruited between August and November 2014 as part of a cross-sectional study.We performed bias-corrected bootstrap tests of mediation using 95%confidence intervals(CI)to determine the mediating effects of body mass index and waist circumference(mediators)on the total effects of HAART exposure(primary predictor)on blood pressure(outcome),while controlling for age,sex and other potential confounders.Results:Waist circumference remained a significant partial mediator of the total effects of HAART exposure on increasing systolic blood pressure(coefficient:1.01,95%CI:0.33 to 2.52,11%mediated)and diastolic blood pressure(coefficient:0.68,95%CI:0.26 to 1.89,9%mediated)after adjusting for age,sex,smoking status,CD4 count and duration of HIV infection.No significant mediating effect was observed with body mass index alone or in combination with waist circumference after adjusting for all potential confounders.Conclusion:Waist circumference significantly mediates the effects of HAART on blood pressure in persons living with HIV,independent of the role of traditional risk factors.The use of waist circumference as a complementary body fat measure to body mass index may improve the clinical prediction of hypertension in HIV-infected patients on antiretroviral therapy.