Antiretroviral Therapy In People Research Articles

PLANNING AND EVALUATION OF BIOEQUIVALENCE STUDIES OF ATAZANAVIR PRODUCTS

The Government of the Russian Federation approved the State strategy of combating the spread of HIV aimed at prevention of HIV epidemic. One of the goals of the Strategy is to increase the coverage of antiretroviral therapy for people infected with HIV, which includes extensive use of generic drugs. In order for a generic drug to be authorised, the applicant has to submit a report on the results of the bioequivalence studies in which the generic product was compared to the reference product. Atazanavir is an antiretroviral drug, which is also the drug of choice for the treatment and prevention of mother-to-child transmission of HIV. The aim of this study was to analyze the protocols and reports of atazanavir products bioequivalence studies, which were submitted for expert examination to the FSBI “SCEEMP” of the Ministry of Health of the Russian Federation, and to prepare recommendations for planning of bioequivalence studies of atazanavir products. The analysis of a number of studies revealed significant differences in the study design and number of subjects. The main reason for these differences is the conflicting data on the intrasubject coefficient of variation of atazanavir, which means that atazanavir may be considered a highly variable drug. The analysis helped to formulate recommendations for the design of bioequivalence studies of atazanavir products, including studies of the maximum dose, studies under fed conditions, and consideration of atazanavir variation when planning the study design.

Supervised Physical Activity and Improved Functional Capacity among Adults Living with HIV: A Systematic Review

Physical activity (PA) combats the effects of multimorbidity and antiretroviral therapy in people living with HIV (PLWH), but PLWH often don't meet recommended PA guidelines. The purpose of our review was to investigate whether supervised PA improved functional capacity in PLWH. Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. Five databases were searched for randomized controlled trials in English, with participants ages 18years and older, and a supervised PA intervention. A database search yielded 8,267 articles, with 15 eligible for review inclusion. We found a low risk of bias within and across studies. Combined aerobic/progressive resistance training (PRT) improved strength, cardiovascular, and flexibility outcomes; aerobic interventions alone showed no significant improvements; PRT improved strength outcomes; yoga or yoga/meditation showed no outcome differences; and t'ai chi showed cardiovascular and flexibility improvements. We found that supervised PA increased functional capacity in PLWH and that self-report was not a reliable assessment.

Ideal Medication-Readiness Cutoff Score for Initiating Antiviral Therapy in HIV Patients

There has been a global consensus since 2016 that antiretroviral therapy (ART) should be initiated following HIV diagnosis regardless of CD4-count test results. Identifying an instrument that is able to accurately assess the readiness of HIV-infected persons for treatment initiation is thus critical. (1) To evaluate the comparative readiness of patients receiving ART and those who are not yet on ART; (2) to evaluate the respective readiness variation within these 2 groups over a one-year period; and (3) to identify the cutoff value for medication readiness that indicates the ideal time to initiate ART. A multicenter cohort study design was conducted and 297 newly diagnosed patients with HIV were enrolled at four time points, including: baseline and at 1, 3-6, and 9-12 months after ART initiation. Data collection included a demographics datasheet, the Chinese version of the HIV Medication Readiness Scale (HMRS), and 2 items, readiness to take ART for a long period of time and confidence in adhering to ART, which were scored using a 10-point Likert scale. Overall, 224 (75.4%) of the participants had initiated ART. Over time, the medication readiness of participants with ART initiation had increased significantly over that of non-ART user (p < .001). The mean scores of the 2-item self-rated readiness scale for patients with ART initiation were significantly greater than those without (p < .001). The cutoff values for HMRS, self-rating readiness for ART, and confidence in adherence to ART were 23.5, 5.5, and 6.5, respectively. The optimal cutoff value of the Chinese version HMRS for evaluating HAART initiation among persons with HIV infection was 23.5. HIV healthcare professionals may apply the Chinese version HMRS and the two simple self-rated items as a clinical tool for quickly assessing the initiation of ART in people living with HIV.

HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis

SummaryBackgroundPretreatment drug resistance in people initiating or re-initiating antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) might compromise HIV control in low-income and middle-income countries (LMICs). We aimed to assess the scale of this problem and whether it is associated with the intiation or re-initiation of ART in people who have had previous exposure to antiretroviral drugs.MethodsThis study was a systematic review and meta-regression analysis. We assessed regional prevalence of pretreatment drug resistance and risk of pretreatment drug resistance in people initiating ART who reported previous ART exposure. We systematically screened publications and unpublished datasets for pretreatment drug-resistance data in individuals in LMICs initiating or re-initiating first-line ART from LMICs. We searched for studies in PubMed and Embase and conference abstracts and presentations from the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society Conference, and the International Drug Resistance Workshop for the period Jan 1, 2001, to Dec 31, 2016. To assess the prevalence of drug resistance within a specified region at any specific timepoint, we extracted study level data and pooled prevalence estimates within the region using an empty logistic regression model with a random effect at the study level. We used random effects meta-regression to relate sampling year to prevalence of pretreatment drug resistance within geographical regions.FindingsWe identified 358 datasets that contributed data to our analyses, representing 56 044 adults in 63 countries. Prevalence estimates of pretreatment NNRTI resistance in 2016 were 11·0% (7·5–15·9) in southern Africa, 10·1% (5·1–19·4) in eastern Africa, 7·2% (2·9–16·5) in western and central Africa, and 9·4% (6·6–13·2) in Latin America and the Caribbean. There were substantial increases in pretreatment NNRTI resistance per year in all regions. The yearly increases in the odds of pretreatment drug resistance were 23% (95% CI 16–29) in southern Africa, 17% (5–30) in eastern Africa, 17% (6–29) in western and central Africa, 11% (5–18) in Latin America and the Caribbean, and 11% (2–20) in Asia. Estimated increases in the absolute prevalence of pretreatment drug resistance between 2015 and 2016 ranged from 0·3% in Asia to 1·8% in southern Africa.InterpretationPretreatment drug resistance is increasing at substantial rate in LMICs, especially in sub-Saharan Africa. In 2016, the prevalence of pretreatment NNRTI resistance was near WHO's 10% threshold for changing first-line ART in southern and eastern Africa and Latin America, underscoring the need for routine national HIV drug-resistance surveillance and review of national policies for first-line ART regimen composition.FundingBill & Melinda Gates Foundation and World Health Organization.

Implications for a policy of initiating antiretroviral therapy in people diagnosed with human immunodeficiency virus: the CAPRA research programme

BackgroundMore than 100,000 people in the UK are living with a human immunodeficiency virus (HIV) infection. There are currently estimated to be around 4000 people newly infected in the UK per year, mostly men who have sex with men (MSM). It has become increasingly clear that antiretroviral therapy (ART) used to treat people infected with HIV also has a profound effect on infectivity. At the initiation of the programme, it was the policy in the UK to initiate ART in people when their cluster of differentiation 4 (CD4) count was approaching 350/µl.ObjectivesTo assess what would be the effectiveness and cost-effectiveness of a policy of immediate initiation of ART at diagnosis among MSM, taking into account the potential reductions in new infections.DesignWe calibrated an individual-based model of HIV transmission, progression and the effect of ART in MSM, informed by a series of studies on sexual behaviour in relation to ART use and the transmission risk in people with viral suppression on ART, and by surveillance data collected by Public Health England.Setting, participants and interventionsThe series of studies used to inform the model included (1) the Antiretrovirals, Sexual Transmission Risk and Attitudes (ASTRA) study, a cross-sectional self-administered questionnaire study of people diagnosed with HIV attending eight HIV outpatient clinics in the UK (2011–12); (2) the Cognitive Impairment in People with HIV in the European Region (CIPHER) study, a study of levels of neurocognitive impairment in HIV-positive ASTRA participants and people from HIV clinics in Rome, Copenhagen and Minsk; (3) the Attitudes to, and Understanding of, Risk of Acquisition of HIV (AURAH) study, a cross-sectional self-administered questionnaire study of individuals who have not been diagnosed as HIV-positive attending 20 genitourinary medicine clinics across the UK (2013–14); (4) a substudy of sexual behaviour among individuals enrolled in an open-label multicentre international randomised trial (from 2013) of immediate versus deferred ART (to CD4 cell counts of 350/µl) in people with CD4 cell counts of &gt; 500/µl [the Strategic Timing of Antiretroviral Therapy (START) trial]; and (5) Partners of People on ART: a new Evaluation of the Risks (PARTNER), an observational multicentre longitudinal study of HIV serodifferent heterosexual and MSM couples, in which the HIV-positive partner is on ART (2010–14).Main outcome measuresThe main outcome measures were the clinical effectiveness and cost-effectiveness of a policy of immediate initiation of ART at diagnosis.ResultsBased on data from studies (i)–(v), we estimated from our modelling work that increases in condomless sex (CLS) among MSM as a whole may explain the increase in HIV infection incidence in MSM epidemics over a time when ART coverage and viral suppression increased, demonstrating the limiting effects of non-condom use on the HIV epidemic among MSM. Accordingly, an increase in the overall proportion of MSM living with HIV who are virally suppressed on ART from the current level of &lt; 60% to 90% without increases in CLS was required to achieve a reduction in the incidence of HIV among MSM to &lt; 1 per 1000 person-years. The incremental cost-effectiveness ratio associated with the fourfold increase in levels of HIV testing and ART at diagnosis required to provide this increase from &lt; 60% to 90% was £20,000 if we assumed continuation of current ART prices. However, this value falls to £3500 if we assume that ART prices will fall to 20% of their current cost as a result of the introduction of generic drugs. Therefore, our evaluation suggests that ART initiation at diagnosis is likely to be highly cost-effective in MSM at a population level, particularly accounting for future lower ART costs as generic drugs are used. The impact will be much greater if levels of HIV testing can be enhanced.LimitationsIt was necessary to make some assumptions beyond the available data in order to extrapolate cost-effectiveness through modelling.ConclusionsOur findings suggest that ART initiation at diagnosis is likely to be cost-effective in MSM. Of note, after this programme of work was completed, results from the main START trial demonstrated benefit in ART initiation even in people with CD4 cell counts of &gt; 500/µl, supporting ART initiation in people diagnosed with a HIV infection.Future workThere is a need for future research into the means of increasing the frequency with which MSM test for HIV.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

Factors Associated With Level of Adherence to Antiretroviral Therapy in People Living with HIV/AIDS at Adama Hospital Medical College Art Clinic, Oromiya Regional State, Ethiopia

Both Human Immunodeficiency Virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS) remain major public health problems in Ethiopia. Good adherence to antiretroviral therapy is necessary to achieve the best virological response, lower the risk of treatment failure and drug resistance, and reduce morbidity and mortality. There are many alterable factors known to affect the treatment adherence. In this regard, there have been very limited researches particularly in Adama. Therefore, this study was aimed to determine the adherence level and its associated factors among adult people living with HIV and attending their clinical care in Adama Hospital Medical College. A hospital based cross sectional study was conducted from October 1, 2016 - January 30, 2017 G. C in Adama Hospital Medical College among 190 PLWHA on ART. Systematic sampling method was used to select study participants. Data was collected by interviewing the clients and review of their medical records using structured questionnaire and checklist. Data entry and analysis was performed using SPSS for windows version 20.0. Descriptive statics was used to summarize socio-demographic and other variables. Bivariate and multivariate analysis was used to evaluate the association between dependent and independent variables. Level of adherence in the week before interview was 92.6. Patients whose initial ART regimen was TDF-3TC-NVP, were 8 times (COR=8.444 (1.678, 42.501)), chance of &lt;95% adherence than patients those started ART with TDF-3TC-EFV regimen. Patients with opportunistic infection were about 8 times (COR=7.593 (2.196, 26.248)) chance of &lt;95% adherence than their counter group respectively. Patients whose waiting time &gt;30 minutes were 8 times (AOR=8.019 (1.161, 55.390)) chance of &lt;95% adherence than their counter group. The level of adherence to ART was relatively higher when compared to others studies done in Ethiopia and other developing countries. But it was sub optimal to WHO adherence level (≥ 95%). The major reasons for missing doses were forgetfulness, away from home (travel) and lack of awareness. The level of adherence was significantly associated with variables like history of opportunistic infection, longer waiting time and starting treatment with TDF-3TC-NVP. This implicates further effort are still needed to push up the adherence to the level of WHO recommendation.

Prevalence of Hypertension and Associated Factors in Patients Living with HIV Followed at the Ambulatory Treatment Center (CTA) of Fann National University Hospital in Dakar

Introduction: The efficacy of antiretroviral therapy in people living with HIV (PLHIV) has been associated with an important increase in metabolic disorders, such as hypertension (HTA). This work allowed us to estimate the prevalence of hypertension in PLHIV and to describe associated factors. Methods: A retrospective, descriptive and analytical study was carried out based on the records of people living with HIV followed at the Ambulatory Treatment Center (CTA), from January 1st 1998 to 31st, December 2014. The WHO criteria were used to diagnose hypertension. Data entry was performed using ESOPE software and data analysis was done using Epi Info software version 3.5.3. A multiple logistic regression was used to identify the risk factors associated with hypertension. Results: During the study period, 3624 patients followed at CTA were included of which 1184 patients (32.7%) had hypertension. The average age was 47. 3 years ±10.5 years, with a sex ratio of 0.7. The most common opportunistic infections at diagnosis were tuberculosis (14.9%) and oral candidiasis (15.3%). The HIV infection was advanced (stage 3 or 4 of WHO classification) for 39% of cases. Overweight and obesity was found in 19.1%. Only 17.6% were treated by protease inhibitors. Higher average age (OR:1,05; IC [1.04 - 1.05], p = 0.000001), higher average BMI (OR:5,3; IC [3.3 - 8.5], p = 0.00001), WHO clinical stage I-II (OR:1,4; IC [1.2 - 1.6], p = 0.00003), and ARV treatment (OR:2,5; IC [1.7 - 3.7], p = 0.000001) are associated with the occurrence of hypertension. Conclusion: The prevalence of hypertension was high among PLHIV and associated factors were: advanced age, high BMI, WHO clinical stages I and II and antiretroviral therapy. Hence, the interest of a systematic screening of hypertension and others cardiovascular risk factors particularly in patients under ARV antiretroviral therapy.

Adesão ao tratamento: construção permanente em busca da autonomia do usuário do sistema único de saúde

A adesão ao tratamento de doenças como a aids é um desafio permanente para os profissionais de saúde pelas implicações que extrapolam o indivíduo doente e atingem não só a família como a comunidade. Aprimorar a adesão à terapia antirretroviral de pessoas que vivem com HIV/aids. O trabalho iniciou em 2012 no Hospital Dia do Hospital de Clínicas da Universidade Estadual de Campinas. A população constitui-se por pessoas que vivem com HIV/aids e outras doenças infecciosas. Em 2012 coletou-se dados de uma amostra aleatória de 141 usuários com aids dos 945 adscritos para avaliar a adesão, considerando-se aderente aquele que ingeriu 95% ou mais dos medicamentos prescritos nos três últimos dias anteriores à entrevista. Dos 141 usuários com adesão analisada em 2012, verificou-se a taxa de adesão de 81,6% sendo maior que a encontrada em 2003, que foi de 73,3%. De março a junho de 2016, faltaram e foram convocados para consultas 268 pacientes e 163 (61%) compareceram às convocações para consulta médica com seguimento do enfermeiro. Realizou-se três pesquisas de satisfação no período. As não conformidades estruturais e de processos foram corrigidas após análise de um check-list com 1479 itens. A clientela adscrita em 2015 foi de 2350 pacientes. O absenteísmo teve redução com a confirmação da consulta médica por telefone. O processo de enfermagem e a confecção da “vitrine da TARV" foram algumas das medidas de segurança. Os pacientes apresentam complexidade social, clínica e terapêutica que podem limitar a elevação dos índices de adesão.

The impact of antiretroviral therapy in resource-limited settings and current HIV therapeutics.

Four million people of the global total of 35million with HIV infection are from South-East Asia. ART is currently utilized by 15million people and has led to a dramatic decline in the mortality rate, including those in low- and middle-income countries. A reduction in sexually transmitted HIV and in comorbidities including tuberculosis has also followed. Current recommendations for the initiation of antiretroviral therapy in people who are HIV+ are essentially to initiate ART irrespective of CD4 cell count and clinical stage. The frequency of HIV testing should be culturally specific and based on the HIV incidence in different key populations but phasing in viral load technology in LMIC is an urgent priority and this needs resources and capacity. With the availability of simplified potent ART regimens, persons with HIV now live longer. The recent WHO treatment guidelines recommending routine HIV testing and earlier initiation of treatment should be the stepping stone for ending the AIDS epidemic and to meet the UNAIDS mission of 90*90*90.

Adherence to antiretrovirals in people coinfected with the human immunodeficiency virus and tuberculosis.

Objective:assess the adherence levels to antiretroviral therapy in people coinfected with HIV/tuberculosis and correlate these levels with the sociodemographic and clinical variables of the study population. Method:cross-sectional study involving 74 male and female adults coinfected with HIV/tuberculosis. For the data collection, a sociodemographic and clinical assessment form and the Antiretroviral Treatment Adherence Assessment Questionnaire were used. For the data analysis, the software STATA version 11 was used, through descriptive statistics, Fisher's chi-square exact test and the probability test. Results:men were predominant (79.7%), between 30 and 39 years of age (35.1%), low income (75.7%) and pulmonary tuberculosis (71.6%). Adherence to antiretroviral therapy was inappropriate in 78.1% of the men; 61.0% of single people; 47.0% unemployed and 76.5% among people gaining less than one minimum wage. A significant difference was observed between compliance and length of use of antiretrovirals (p=0.018), sexual orientation (p=0.024) and number of children (p=0.029). Conclusion:the coinfected patients presented inappropriate adherence to the antiretrovirals, a fact that negatively affects the health conditions of the people living with HIV/tuberculosis coinfection. A statistically significant correlation was found between the levels of adherence and some sociodemographic and clinical characteristics.

Drop out of antiretroviral therapy in people living with AIDS/HIV and related factors in Nanjing and Yuncheng

To understand the incidence of drop out of antiretroviral therapy (ART) in people living with AIDS/HIV and related factors in Nanjing, Jiangsu province, and Yuncheng, Shanxi province. Retrospective cohort analysis was conducted. The cumulative incidence curves of drop out of ART, mortality and drug withdrawal were drawn with Kaplan-Meier method. The related factors were identified with Cox proportional hazards regression model. A total of 1 006 patients were included in Yuncheng, the median length of ART follow-up was 49.59 months (QR: 20.02-92.84), and 976 patients were included in Nanjing, the median length of ART follow-up was 19.93 months (QR: 11.48-34.07). The cumulative incidence of drop out of ART at 3 months, 6 months, 1 year, 2 years, 4 years, 8 years after ART was 8.19%, 9.23%, 11.08%, 13.75%, 17.74%, 27.66% in Yuncheng, and 3.01%, 5.17%, 7.47%, 10.97%, 17.45%, 28.72% in Nanjing respectively. Age, marital status, infection route, baseline CD4 cell count, the clinical stage classified by WHO at the end of the observation were correlated with the drop out of ART. In order to reduce the drop out of ART among people living with AIDS/HIV, it is necessary to conduct effective interventions targeting the patients with young age, the patients who divorced/widowed, the patients who were intravenous drug users, the patients with higher CD4 cell count at the beginning of ART and clinical stage III or IV at the end of the follow-up and increase the coverage of HIV test.

Co-trimoxazole prophylaxis in adults, including pregnant women, with HIV: a systematic review and meta-analysis

Co-trimoxazole prophylaxis is used to reduce morbidity and mortality in people with HIV. We systematically reviewed three topics related to co-trimoxazole prophylaxis to update WHO guidelines: initiation, discontinuation, and dose. We searched PubMed, Embase, WHO Global Index Medicus, and clinical trial registries in November, 2013, for randomised controlled trials and observational studies including co-trimoxazole prophylaxis and a comparator group. Studies were eligible if they reported death, WHO clinical stage 3 or 4 events, admittance to hospital, severe bacterial infections, tuberculosis, pneumonia, diarrhoea, malaria, or treatment-limiting adverse events. Infant mortality, low birthweight, and placental malaria were additional outcomes for the comparison of co-trimoxazole prophylaxis and intermittent preventive treatment for malaria in pregnant women (IPTp). We compared a dose of 480 mg co-trimoxazole once a day with one of 960 mg co-trimoxazole once a day. We used a 10% margin for non-inferiority and equivalence analyses. We used random-effects models for all meta-analyses. This study is registered with PROSPERO, number CRD42014007163. 19 articles, published from 1995 to 2014 and including 35 328 participants, met the inclusion criteria. Co-trimoxazole prophylaxis reduced rates of death (hazard ratio [HR] 0·40, 95% CI 0·26-0·64) when started at CD4 counts of 350 cells per μL or lower with antiretroviral therapy (ART) worldwide. Co-trimoxazole prophylaxis started at higher than 350 cells per μL without ART reduced rates of death (0·50, 0·30-0·83) and malaria (0·25, 0·10-0·57) in Africa. Co-trimoxazole prophylaxis was non-inferior to IPTp with respect to infant mortality (risk difference [RD] -0·05, 95% CI -0·12 to 0·02), low birthweight (0·00, -0·07 to 0·07), and placental malaria (0·00, -0·10 to 0·10). Co-trimoxazole prophylaxis continuation after ART-induced recovery with CD4 counts higher than 350 cells per μL reduced admittances to hospital (HR 0·42, 95% CI 0·22-0·80), pneumonia (0·73, 0·61-0·88), malaria (0·03, 0·01-0·10), and diarrhoea (0·61, 0·48-0·78) in Africa. A dose of 480 mg co-trimoxazole prophylaxis once a day did not reduce treatment-limiting adverse events compared with 960 mg once a day (RD -0·07, 95% CI -0·52 to 0·39). Co-trimoxazole prophylaxis should be given with ART in people with CD4 counts of 350 cells per μL or lower in low-income and middle-income countries. Co-trimoxazole prophylaxis should be provided irrespective of CD4 count in settings with a high burden of infectious diseases. Pregnant women with HIV in Africa should use co-trimoxazole rather than IPTp to prevent malaria complications in infants. Further research is needed to inform dose optimisation and co-trimoxazole use in the context of expanded ART in different epidemiological settings. None.

Qualidade de vida e adesão à medicação antirretroviral em pessoas com HIV

Objetivo Avaliar e correlacionar a qualidade de vida e a adesão à terapia antirretroviral em pessoas com HIV. Métodos Estudo transversal, desenvolvido com 45 pessoas com HIV em tratamento ambulatorial. Os instrumentos utilizados foram: questionário para avaliação da adesão ao tratamento antirretroviral (CEAT-VIH) e escala para avaliação da qualidade de vida em pessoas com HIV (HAT-QoL). Foi realizada análise descritiva e empregado o teste de correlação linear de Spearman. Resultados A qualidade de vida mostrou-se comprometida nos domínios relacionados às atividades gerais; sexuais; preocupação com a saúde, com o sigilo, com questões financeiras; e conscientização sobre o HIV. Houve predomínio da adesão inadequada em 51,3% dos participantes. A correlação entre os escores das escalas mostrou significância estatística nos domínios relacionados à medicação e confiança no profissional. Conclusão A qualidade de vida apresentou comprometimento em seis domínios da escala e a adesão encontrou-se inadequada na maioria das pessoas com HIV.

Service integration: opportunities to expand access to antiretroviral therapy for people who inject drugs in Tanzania.

No abstract available. Keywords: HIV/AIDS; antiretroviral therapy; methadone; people who inject drugs; service integration; implementation science. (Published: 21 July 2015) Citation: Lambdin BH et al. Journal of the International AIDS Society 2015, 18 :19936 http://www.jiasociety.org/index.php/jias/article/view/19936 | http://dx.doi.org/10.7448/IAS.18.1.19936

Second-line failure and first experience with third-line antiretroviral therapy in Mumbai, India

BackgroundThere are limited data on the failure of second-line antiretroviral therapy (ART) and the use of third-line ART in people living with HIV in resource-limited settings. Since 2011, the Médecins Sans Frontières (MSF) HIV/tuberculosis programme in Mumbai, India, has been providing third-line ART to patients in care.ObjectiveTo describe the experiences and programmatic challenges during management of suspected second-line ART failure and third-line ART therapy for patients living with HIV, including the use of HIV viral load (VL) testing.DesignThis was a retrospective, observational cohort study of patients with suspected second-line ART treatment failure, who were followed for at least 12 months between January 2011 and March 2014.ResultsA total of 47 patients with suspected second-line failure met the inclusion criteria during the study period. Twenty-nine of them (62%) responded to enhanced adherence support, had a subsequent undetectable VL after a median duration of 3 months and remained on second-line ART. The other 18 patients had to be initiated on a third-line ART regimen, which consisted of darunavir–ritonavir, raltegravir, and one or more appropriate nucleoside or nucleotide reverse transcriptase inhibitors, based on the results of HIV genotype testing. Of the 13 patients for whom follow-up VL results were available, 11 achieved virological suppression after a median duration of 3 months on third-line ART (interquartile range: 2.5–3.0). No serious treatment-related adverse events were recorded.ConclusionsWith intensive counselling and adherence support in those suspected of failing second-line ART, unnecessary switching to more expensive third-line ART can be averted in the majority of cases. However, there is an increasing need for access to third-line ART medications such as darunavir and raltegravir, for which national ART programmes should be prepared. The cost of such medications and inadequate access to VL monitoring and HIV genotype testing are currently major barriers to optimal management of patients failing second-line ART.

HIV treatment as prevention: contradictory perspectives from dynamic mathematical models.

The preventative effects of antiretroviral therapy for people with HIV have been debated since they were first raised. Models commenced studying the preventive effects of treatment in the 1990s, prior to initial public reports. However, the outcomes of the preventive effects of antiretroviral use were not consistent. Some outcomes of dynamic models were based on unfeasible assumptions, such as no consideration of drug resistance, behavior disinhibition, or economic inputs in poor countries, and unrealistic input variables, for example, overstated initiation time, adherence, coverage, and efficacy of treatment. This paper reviewed dynamic mathematical models to ascertain the complex effects of ART on HIV transmission. This review discusses more conservative inputs and outcomes relative to antiretroviral use in HIV infections in dynamic mathematical models. ART alone cannot eliminate HIV transmission.

Dyslipidaemia in HIV-1-infected patients receiving protease inhibitors after initial treatment with first-line-based non-nucleoside reverse transcriptase inhibitors: a cross-sectional study

ObjectivesLipid abnormalities associated with antiretroviral therapy in people with HIV infection are more frequent with protease inhibitors (PI)-based regimens. Whether effects extend to patients receiving a PI subsequent to failure...

Alterations in Immune Function are Associated with Liver Enzyme Elevation in HIV and HCV Co-infection after Commencement of Combination Antiretroviral Therapy

The cause of liver enzyme elevation during combination antiretroviral therapy in people with human immunodeficiency virus and hepatitis C virus co-infection is unclear. We followed 12 subjects (five with alanine transaminase elevation) for 24 weeks after combination antiretroviral therapy commencement. Immune responses against hepatitis C virus, human immunodeficiency virus and other viruses were assessed by interferon-γ ELISpot. Plasma cytokines, chemokines and anti-hepatitis C virus antibody levels were measured. Those with liver enzyme elevation had higher ELISpot responses both against hepatitis C virus non-structural regions and other viral antigens, and their anti-hepatitis C virus antibody levels were consistently higher, suggesting that reconstitution of both hepatitis C virus-specific and non-hepatitis C virus-specific immune responses may be associated with liver transaminase elevation during combination antiretroviral therapy.

HIV Diagnosis at CD4 Count Above 500 Cells/mm3 and Progression to Below 350 Cells/mm3 Without Antiretroviral Therapy

A trial to evaluate the risks and benefits of initiation of antiretroviral therapy (ART) in patients with high CD4 count (eg, > or =500 cells/mm3), in comparison with deferral (eg, to <350 cells/mm3), merits consideration. Two issues for consideration in designing such a trial are the proportion of patients seen in clinics who present with high CD4 count and the time it will take for those randomized to deferring ART to reach a level where ART must be initiated. Among 13,572 patients in the UK CHIC Study presenting since 1996, 3631 (27%) had a count > or =500 cells/mm3. Among 4268 ART-naive patients with at least one CD4 count in the 500 to 650 cells/mm3 range, the median time to <350 cells/mm3 (or start of ART) was 2.5 years, with a range of 2.1 to 3.1 years depending on the analysis approach. Viral load at baseline was a strong predictor of the time taken for the CD4 count to reach <350 cells/mm3, with the median ranging from 0.7 years in those with viral load > or =500,000 copies/mL to 4.7 years in those with <1000 copies/mL. This provides timely background data on ART-naive patients seen in clinical practice to support design of a trial to compare immediate with deferred ART in people with high CD4 count.

Depression, social support and adherence to highly active antiretroviral therapy in people living with HIV/AIDS

The present study investigated the prevalence of depression in HIV-positive individuals and its association with adherence to highly active antiretroviral therapy (HAART). HIV-positive (n = 80) and HIV-negative (n = 20) participants were assessed for depression and adherence via clinical interview and self-reporting. Fourteen percent of the HIV-seropositive group met the criteria for current mood disorder compared with 5% of controls. Similarly, 39% of the HIV-seropositive participants met the criteria for a past major depressive episode compared with 15% of controls. Non-adherence to HAART was reported by 30.5% of those prescribed HAART and was significantly associated with living alone and relationship status. The present study found compromised psychological health in people living with HIV infection. It is recommended that health professionals continue to screen for depression, relationship status and living situation to ensure adherence to HAART.