Antiretroviral Regimen Changes Research Articles

Lung Transplantation in HIV Patients

<h3>Purpose</h3> Limited published data exist on outcomes related to lung transplantation (LTx) in human immunodeficiency virus (HIV)-infected individuals. <h3>Methods</h3> We conducted a multicenter retrospective study of LTx in HIV- infected patients and describe key transplant- and HIV-related outcomes. <h3>Results</h3> We identified 22 HIV-infected LTx recipients across 25 transplant centers from 2007 through 2021. At transplantation, mean age was 53 [46 - 59] years, 55% were male. Two (9%) patients had an history of previous opportunistic infection and AIDS status. Pretransplant CD4 T cell count was 514 [351 - 670] cell/mm3 and RNA viral load was negative in all patients and their values did not change significantly post operatively. Due to calcineurin inhibitor interactions, 3 (15%) patients required an antiretroviral regimen change before LTx. Main indications for LTx were pulmonary arterial hypertension in 7 (32%), fibrosis in 5 (23%) and cystic fibrosis in 3 (14%). LTx procedure was predominantly bilateral-lung transplantation (91%). Immunosupression was giving according to local protocols including induction in 7 (32%) patients. During first post-LTx year, acute cellular rejection, antibody-mediated rejection, and infections requiring hospitalization occurred in 7 (37%), 2 (11%) and 8 (40%), respectively. During the median [range] follow-up of 25 [0.1-172] months, 26% and 14% of patients developed chronic lung allograft dysfunction and malignancy, respectively. Posttransplant survival rates after 1, 3, and 5 years were 79%, 79%, and 79%, respectively. At last news evaluation, 59% of the patients were fully active and independent. <h3>Conclusion</h3> Apart from early infection rates, survival rates and post-operative outcome were similar to their HIV-uninfected LTx recipients. At last follow-up, more than half of the patients had near-normal functional status.

Antiretroviral regimen change among people infected with HIV: evidence from a cross-sectional study in China

Abstract Background: The rate of death among people living with HIV/AIDS has decreased significantly as a result of treatment with highly active antiretroviral therapy (HAART). However, the issues of drug induced toxicities and complexity of current HAART regimens has remained of great concern. The aim of this study was to determine factors influencing antiretroviral regimen changes among people living with HIV/AIDS in China. Methods: This retrospective study collected data through face-to-face interviews with people living with HIV/AIDS who were receiving HAART, and gathered relevant information from infectious disease hospitals. The following information were collected: social-demographic characteristics, antiretroviral therapies, CD4 cell counts, virus loads, reasons for changing medication and other related data. Mean and percentages were used to describe the frequency of regimen change among patients, and binary logistic regression was employed to test the factors influencing regimen change. Results: 1,123 people who had experienced regimen change were included in the analysis. On average, patients remained on HAART for 10.2 months before changing regimen, and the average CD4 cell count and viral load (VL) were 383.1 cells/μl and 28,132.4 copies/mL respectively when changing regimen. The reasons for modification were determined as treatment failure (52.5%), adverse reactions (32.3%), and other reasons including pregnancy (15.2%). There are significant differences in regimen change among people with different genders (P Conclusion: Treatment failure was the main reason for the change of HAART regimen. Males, drug users, people on long-term medication and those with lower initial CD4 cell counts when starting HAART were most likely to change regimen.

Determinants of anti-retroviral regimen changes among HIV/AIDS patients of east and west Wollega zone health institutions, Oromia region, west Ethiopia: a cross-sectional study

BackgroundHuman Immunodeficiency Virus (HIV) is one of the main causes of morbidity and mortality; because of this it continues to be a major global public health concern. It has believed to kill more than 34 million lives so far. Sub Saharan Africa constitutes about 70% of people living with HIV among the 37 million on the globe. This region, accounted for more than two third of the global new HIV infections and about 15 million (40%) were receiving antiretroviral therapy (ART) at the end of 2014 throught the world. ART has fundamentally changed the treatment of HIV and transformed this infection from a disease of high mortality to chronic and medically managed disease. The issues of drug induced toxicities & complexity of current highly active antiretroviral therapy (HAART) regimens has remained of great concern. The aim of this study was to determine factors leading to antiretroviral regimen changes among HIV/AIDS Patients in the study area.MethodsA facility based retrospective cross-sectional study was conducted from April 28, 2017 to May 30, 2017 in the ART clinics of east and west Wollega zone health institutions using a pre-tested data collecting form and chart review. The sample included the 243 patients whose medication had been switched.ResultsMajority 145 (59.67%) of the patients had been on ART for > 10 years duration. More than half 126(51.9%) of the patients had received tuberculosis (TB) treatment and almost three out of five patients (57.2%) had received isoniazid & cotrimoxazole prophylaxis. The most common reason for regimen change was peripheral neuropathy 146(60.1%) and the most common medication for this reason was stavudine, lamivudine and neverapine based 108(44.44%).ConclusionsThe number of patients who changed ARV drug in our resource constrained setting present a challenge to the restricted treatment choices that we currently own. Less toxic and better-tolerated HIV treatment options should be available and used more frequently.

Antiretroviral changes during the first year of therapy.

The Brazilian HIV/AIDS management and treatment guideline (PCDT), published in 2013, recommends and standardizes the use of highly active antiretroviral therapy (HAART) in all adult patients, in spite of LTCD4 count. This study aimed to analyze the first year of HAART use in patients from a reference center on HIV/AIDS management in Fortaleza, Ceará. This descriptive study reviewed all prescription forms of antiretroviral regimens initiation and changes from January to July 2014. All antiretroviral regimen changes that occurred during the first year of therapy were evaluated. Data were analyzed with SPSS version 20. Mean, standard deviation and frequency, Student's t and Mann-Whitney tests calculations were used, with significance at p<0.05. From 527 patients initiating HAART, 16.5% (n=87) had a regimen change in the first year. These patients were mostly male (59.8%; n=52), aged 20 to 39 years, with only one HAART change (72.4%; n=63). Efavirenz was the most often changed drug, followed by tenofovir, zidovudine and lopinavir/ritonavir. Mean time of HAART changes was 120 days, with adverse reactions as the most prevalent cause. HAART was effective in decreasing viral load since second month of treatment (p=0.003) and increasing LTCD4 lymphocytes since fifth month (p<0.001). The main cause of initial HAART changes was adverse reaction and most patients had only one change in the HAART regimen. HAART prescription was in accordance to the PCDT from 2013.

Excellent retention, virologic and clinical outcomes after transitioning from an antiretroviral treatment clinical trial to locally-provided care and treatment in Africa

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Little is known about outcomes among clinical trial participants following completion of study-provided care and treatment in resource limited settings. We sought to describe outcomes among HIV clinical trial participants after transitioning to local routine care in Africa&lt;span lang="EN-IN"&gt;. &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; In the OCTANE study, 741 women with CD4 &amp;lt;200 cells/mm&lt;sup&gt;3&lt;/sup&gt; in 7 African countries were randomized to initiate antiretroviral treatment (ART) with tenofovir/emtricitabine (TDF/FTC) plus either lopinavir/ritonavir (LPV/r) or nevirapine (NVP). When study-specified ART ended (48-191 weeks after study entry), participants transitioned to locally-provided HIV care and non-study ART. Consenting participants were interviewed and had toxicity labs, CD4 and HIV-1 RNA testing, and clinical outcomes assessed at 12 and 72 weeks after transition to local care&lt;span lang="EN-IN"&gt;.&lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Five hundred thirteen (77%) of the 669 women in follow-up at completion of the interventional trial participate in the extended follow-up. 513 women, 476 (93%) had HIV-1 RNA &amp;lt;400 cp/mL at time of transition, and 489 (95%) completed follow-up. Seventy-seven women (19%) had a total of 99 antiretroviral regimen changes during post-trial follow-up. 30% of the 99 regimen changes-were due to lack of local drug availability. Thirteen (3%) women had Grade ≥3 laboratory abnormalities and 3 experienced worsening of the WHO HIV stage. Two women died. Eighty-nine percent of 484 with results had HIV-1 RNA ≤400 cp/mL at 72 weeks after transition to local non-study HIV care and treatment&lt;span lang="EN-IN"&gt;. &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; The vast majority of women were able to continue key components of their ART and to maintain virologic suppression through 72 weeks of locally-provided post-study care.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial registration:&lt;/strong&gt; ClinicalTrials.gov NCT00089505&lt;/p&gt;

Characterizing Patients with Very-Low-Level HIV Viremia: A Community-Based Study.

Very-low-level viremia (VLLV) is a relatively new concept in the realm of human immunodeficiency virus (HIV) care. Newer generation assays are now able to detect plasma HIV RNA Viral Load (VL) levels as low as 20 copies/mL. The authors characterized patients with VLLV (VL between 20 and 50 copies/mL) in order to identify possible risk factors associated with virologic failure and poor clinical outcomes. The authors reviewed 119 consecutive charts of patients with VLLV. Sociodemographic data were extracted and viral load and CD4 counts were trended over a 12 month period (February 2013-February 2014). Regression analysis was used to assess the role of different factors on virologic failure at 1 year. Of the study participants with evaluable data (n = 100), the median age was 53 years (interquartile range: 43-57.5), 67% were nonwhite, 34% were women, 58% were smokers, 47% were alcoholics, 58% had a history of intravenous drug use, and 40% were coinfected with hepatitis C virus. More than half of the participants had 3 or more comorbidities and their HIV pill burden was high (more than 2 pills daily). After 12 months, 65 participants achieved undetectable viral load levels, whereas 15 experienced virologic failure (2 consecutive viral loads > 50 copies/mL) and the remaining 20 had persistent VLLV. In the virologic failure group, there was a predominance of white males (66%) with a significant number of comorbidities and pill burden. Univariate logistic regression suggested that there was a difference between the failure versus nonfailure groups in terms of race, ethnicity, and alcohol use. Multivariate regression with virological failure as the outcome suggested a trend only in terms of participant's alcohol use. Most patients with initial VLLV (70%) achieved virologic suppression at 1 year with no antiretroviral therapy changes. Thus, VLLV does not necessarily predict virologic failure and should not prompt more frequent clinic visits or antiretroviral regimen changes. Further research is needed in order to determine the predictors of virologic failure in this subset of patients and the clinicians' attitude toward VLLV.

Confirmation of factors that influence antiretroviral regimen change and the subsequent patient outcomes at a Regional Hospital in rural KwaZulu-Natal.

BackgroundTreatment failure (TF) and adverse drug reactions (ADRs) are the main indications for antiretroviral therapy (ART) regimen change. Identification of factors influencing regimen change and subsequent health outcomes of patients after regimen change is essential in providing a sustainable and effective antiretroviral roll-out campaign.AimTo confirm the factors that influence antiretroviral regimen change and to evaluate patient outcomes post regimen change.MethodsA retrospective chart analysis of 269 HIV-infected non-pregnant patients (age >18 years), who underwent an antiretroviral (ARV) regimen change and were followed up for approximately one year since initiation, was undertaken at a Provincial Hospital ARV Clinic in KwaZulu-Natal, from January 2008 to December 2012.ResultsOf the 269 patients, there were 200 females (75%). Most patients were between the ages 30 and 44 (57.6%). Only five patients had coexisting tuberculosis (TB) infection (2%). The most common first-line ART regimen to be changed was stavudine (D4T)/lamivudine(3TC)/ efavirenz(EFV) n = 111(41%). The most common regimen patients were changed to was tenofovir (TDF)/3TC/EFV n = 89(33%). Stavudine was the most commonly substituted drug (35.5%). Lipodystrophy was the most common ADR (56.8%). ADR was the indication for ART regimen change in 175 patients (65%), whilst TF accounted for ART regimen change in 94 patients (35%). Immunological success (CD4 counts) was shown after regimen change (374.21 ± 243.16 vs. 456.09 ± 250.07, CI: 0.95, p < 0.001). Undetectable viral loads were measured in 172/205 (83.9%) patients post regimen change.ConclusionADRs were the main cause for antiretroviral regimen change. Stavudine was the most substituted drug with lipodystrophy being the most common side effect. Coexisting TB infection did not influence regimen change. Immunological and virological success was shown after regimen modification.

Characteristics associated with virologic failure in high-risk HIV-positive participants with prior failure: a post hoc analysis of ACTG 5251

Patients with prior virologic failure (VF) are at an increased risk of subsequent failure, emergence of resistance, and death. This analysis identifies outcomes and correlates of VF in a high-risk population.Methods: A5251 was designed to evaluate an enhanced adherence counseling intervention delivered by nurses from a central call site on virologic suppression. Due to slow enrollment, the study was closed prematurely and revised study endpoints were evaluated (week 24 VF (HIV-1 RNA ≥200 copies/ml) and non-perfect adherence (<100% self-reported using both the ACTG adherence questionnaire and visual analog scale (VAS)).Results: Fifty-nine participants were enrolled, 43 (73%) black non-Hispanic and 23 (39%) women. Median prior antiretroviral regimen changes were three and the co-morbidity in this population was higher than typical for HIV clinical trials. At week 24 (n = 41), 24 (59%) failed to reach virologic suppression (HIV-1 RNA <200 copies/ml) and 25 (63%) reported non-perfect adherence. Higher depression (CES-D10) and adverse illness perceptions (IPQ-B) were associated with week 24 non-adherence. Early clinical assessments (week 12 HIV-RNA ≥200 copies/mL and non-perfect adherence) as well as higher depression and adverse illness perceptions were associated with week 24 VF.Discussion: In this high-risk population, the proportion of participants with suboptimal adherence and VF was unacceptably high. Interventions to address this treatment gap are clearly needed. Depression and a higher illness perception score, failure to achieve virologic suppression by week 12, and less than perfect adherence could be used to target individuals for early interventions in treatment-experienced, high-risk individuals at high risk for VF.

Evaluation of the efficacy and safety of changes in antiretroviral regimens for HIV-infected patients.

Antiretroviral therapy is now available for HIV-infected patients, and so-called highly active antiretroviral therapy (HAART) now makes it possible to strongly suppress viral proliferation and restore immunity. However, the development of new drugs and regimens for HAART is still in progress, with the aim of overcoming a number of associated problems. For this purpose, changes in the prescribed anti-HIV drugs are often made. In the present study, we attempted to clarify the actual effects of such treatment modifications in patients who had been started on HAART. We retrospectively investigated HIV-infected patients who had been started on HAART at Kitasato University Hospital between April 1997 and March 2013. The patients' backgrounds, characteristics and laboratory data were established from the hospital medical records. The total follow-up time was 447.3 person-years. The patients remained on their initial regimen for a median period of 2040 days, and 39 patients took a second regimen for a median of 2714 days. There was no treatment failure due to regimen change. The reason for the regimen change was adverse effects in 49 cases, poor adherence/virological failure in 4, immunological failure in 3, patient request in 2, and proposals made by health care workers, or for simplification, in 11. The number of patients who required regimen change due to renal dysfunction showed a gradual increase. The number of times anti-HIV drugs were taken per day was not altered when the regimen changed, being mainly once or twice a day. In the present study, there were no instances of treatment failure due to regimen change. Through appropriate regimen change, it is possible to avoid serious adverse effects, and to improve patient adherence. Further adverse effects associated with long-term antiretroviral therapy, and reduction of adherence through medication fatigue should be considered. Drug selection and regimen change should be considered in relation to long-term prognosis.

Causes for antiretroviral regimen change among HIV/AIDS patients in Addis Ababa, Ethiopia.

Highly active antiretroviral therapy has markedly decreased the morbidity and mortality due to HIV/AIDS. Once antiretroviral therapy (ART) is initiated, patients generally remain on medications indefinitely. A switch in the antiretroviral regimen is often necessary because of both acute and chronic toxicities, concomitant clinical conditions, and development of virologic failure. The objective of this study was to assess the causes of initial highly active antiretroviral therapeutic regimen changes among patients on ART in Addis Ababa, Ethiopia. This was a retrospective cross-sectional study conducted from January 1 to March 1, 2010 in two primary hospitals and one health centre in central Ethiopia. Information cards of HIV/AIDS patients who have had their antiretroviral regimen switched were reviewed. Data from patients below 18 years old and those who did not switch HAART regimen were excluded. Data were then analyzed using SPSS for windows version 16.0. A total of 300 patients' information card was reviewed and the mean age of the patients was 38.6±7 years. Females accounted for 59% (177) of the total patients. The most common first regimen before first switch was D4T/3TC/NVP (63%) and D4T/3TC/EFV (18%). The main reasons for modification were toxicity (65%), co-morbidity (25%), pregnancy (5%) and treatment failure (3%). The main types of toxicities observed were peripheral neuropathy (39%), rash (20%) and anaemia (13.33%). Drug toxicity was the main reason for modification of initial antiretroviral regimen and initial Efavirenz-based regimens are less likely to be changed. The occurrence of drug toxicity should be assessed early among patients commencing HAART and health professionals should be empowered to make appropriate regimen changes.

Improving adherence and clinical outcomes through an HIV pharmacist's interventions

Human immunodeficiency virus (HIV) positive individuals who adhere to their antiretroviral (ARV) regimens are more likely to achieve suppressed HIV viral load and improved immunologic response; however, for most patients, medication adherence remains a challenge. Prior studies have shown that clinical pharmacists contribute to the management of HIV-infected patients; but due to variability in clinical responsibilities and study limitations, their value has not been fully realized. The objective of this study was to investigate clinical outcomes of an HIV clinical pharmacist's interventions at Kaiser Permanente Medical Care Program, who utilizes medication expertise to provide recommendations for ARV regimen changes. The pharmacist suggests new ARV regimens in order to attain virologic suppression, improve immunologic response, or minimize ARV adverse effects, while aiming to optimize patients' adherence by decreasing pill burden and/or dosing frequency. This retrospective study assessed the effectiveness of the pharmacist's interventions that occurred between 11 September 2006 and 30 September 2008 on pill burden, dosing frequency, and medication adherence. Additionally, CD4+ cell count and HIV viral load pre- and post-intervention were evaluated. Medication adherence was assessed utilizing electronic pharmacy refill records and calculated based on the formula: [(pills dispensed/pills prescribed per day)/days between refills] x 100. From a cohort of 75 patients, mean daily pill quantity and dosing frequency decreased from 7.2 pills/day and 2.0 times/day in the control phase to 5.4 pills/day and 1.5 times/day in the study phase, respectively (p<0.001). Medication adherence increased from a mean of 81% in the control phase to 89% in the study phase (p=0.003). Clinical outcomes measured by CD4+ cell count and CD4% were statistically improved and more individuals achieved undetectable HIV viral loads post-intervention (p<0.001). In conclusion, HIV clinical pharmacists may play an important role in reducing pill burden and dosing frequency, increasing medication adherence, and improving clinical outcomes.

Discontinuation of standard first‐line antiretroviral therapy in a cohort of 1434 Malawian children

The standard first-line antiretroviral (ART) regimen in Malawi for both adults and children is a fixed-dose combination tablet containing stavudine (d4T), lamivudine (3TC) and nevirapine (NVP). This regimen has been shown to yield satisfactory virologic and immunologic outcomes in children. Published studies have described insights into discontinuation of first-line regimen and toxicities of ART in adults, but similar studies in paediatric populations are lacking.A retrospective cohort study was undertaken to assess reasons for discontinuation of the standard first-line ART regimen (d4T/3TC/NVP) in a paediatric population. In total, 1434 patients met eligibility criteria and were included. The cohort had mean and median age at ART initiation of 4.7 years and 2.9 years, respectively (range: 0.1 months-18.7 years). The gender distribution was 47% female and 53% male. Median follow-up time on ART was 1.8 years (range: 2 weeks-3.9 years). A majority (96.2%) of patients were on the standard first-line ART regimen, while 3.8% (54) were on a different regimen. Twenty-eight patients (2.0%) were on an alternative first-line regimen due to toxicities, 22 patients (1.5%) were on a second-line regimen due to ART failure, and four patients (0.3%) were on a non-standard regimen for other clinical reasons.Of the 28 patients who experienced toxicities requiring ART regimen change, 60.7% (17) were caused by NVP, 39.3% (11) by d4T, and none by 3TC. The median time from first-line ART initiation to alternative first-line ART was two months (range: 10 days-28.1 months); 60.7% of patients on alternative first-line ART were male. Average time on ART until switch to second-line ART regimen was 16.3 months (SD: 9.3 months). The probability of failure after one year on first-line regimen was 1.6% (95% CI: 0.9-2.6).There was no compelling evidence in this cohort, representing approximately 10% of all children on ART in Malawi, to support changing the standard paediatric first-line regimen based on early toxicities or failure. However, experience from the national adult cohort, longer term follow up of the paediatric cohort in this study, emerging data on resistance after single-dose NVP containing mother to child transmission antiretroviral prophylaxis, and new 2009 World Health Organization ART recommendations may influence national policy change to a different first-line regimen.

Trends in Antiretroviral Therapy Use and Survival Rates for a Large Cohort of HIV-Infected Children and Adolescents in the United States, 1989-2001

In the United States, HIV-infected children and adolescents are aging and using antiretroviral (ARV) therapy for extended periods of time. To assess trends in ARV use and long-term survival in an observational cohort of HIV-infected children and adolescents in the United States. The Pediatric Spectrum of HIV Disease Study (PSD) is a prospective chart review of more than 2000 HIV-infected children and adolescents. Patients were included in the analysis from enrollment until last follow-up. Triple-ARV therapy use (for 6 months or more) increased from 27% to 66% during 1997 to 2001 (P < 0.0001, chi for trend). The proportion of patients receiving 3 or more sequential triple-therapy regimens also increased from 4% to 17% during 1997 to 2001 (P < 0.0001, chi for trend), however, and the durability of triple-therapy regimens decreased from 13 to 7 months from the first to third regimen. Survival rates for the 1997 to 2001 birth cohorts were significantly better than for the 1989 to 1993 and 1994 to 1996 cohorts (P < 0.0001). Survival rates in the PSD cohort have increased in association with triple-ARV therapy use. With continued changes in ARV regimens, effective modifications in ARV therapy and the sustainability of gains in survival need to be determined.

Impact of Antiretroviral Regimen Switches on Adherence

Purpose: An understanding of the situations in which adherence lapses occur is critical to the design of effective interventions to enhance adherence. We investigated whether a switch in antiretroviral medications affected adherence by examining a prospective observational cohort of 128 patients who began a new antiretroviral regimen. Method: Adherence was measured using electronic devices, pill counts, and self-reports, which were combined into a composite adherence measure and expressed as the proportion of prescribed medication taken. Results: During 1,056 person-months of follow-up, 129 medication regimen changes occurred among 84 patients (66% of participants). Among the 89 analyzable switches (representing 66 patients), the most common reasons for switch included pill to liquid ritonavir (n = 26), gastrointestinal intolerance (n = 11), virologic failure (n = 8), and peripheral neuropathy (n = 7). Overall, mean adherence prior to regimen switch exceeded mean adherence after regimen switch (0.75 vs. 0.70; p = .035). Among subgroups of switches, adherence decreased significantly after switching from pill to liquid ritonavir (0.83 vs. 0.68; p < .001). When this group was excluded, there was no change in adherence after switches (0.72 vs. 0.71; p = .74). Conclusion: Antiretroviral regimen changes are not associated with adherence improvement and may be associated with declining adherence when a new regimen is unpalatable. Antiretroviral regimen changes should trigger reassessment of adherence and, when appropriate, adherence intervention.

Impact of Antiretroviral Regimen Switches on Adherence

Purpose: An understanding of the situations in which adherence lapses occur is critical to the design of effective interventions to enhance adherence. We investigated whether a switch in antiretroviral medications affected adherence by examining a prospective observational cohort of 128 patients who began a new antiretroviral regimen. Method: Adherence was measured using electronic devices, pill counts, and self-reports, which were combined into a composite adherence measure and expressed as the proportion of prescribed medication taken. Results: During 1,056 person-months of follow-up, 129 medication regimen changes occurred among 84 patients (66% of participants). Among the 89 analyzable switches (representing 66 patients), the most common reasons for switch included pill to liquid ritonavir (n = 26), gastrointestinal intolerance (n = 11), virologic failure (n = 8), and peripheral neuropathy (n = 7). Overall, mean adherence prior to regimen switch exceeded mean adherence after regimen switch (0.75 vs. 0.70; p = .035). Among subgroups of switches, adherence decreased significantly after switching from pill to liquid ritonavir (0.83 vs. 0.68; p < .001). When this group was excluded, there was no change in adherence after switches (0.72 vs. 0.71; p = .74). Conclusion: Antiretroviral regimen changes are not associated with adherence improvement and may be associated with declining adherence when a new regimen is unpalatable. Antiretroviral regimen changes should trigger reassessment of adherence and, when appropriate, adherence intervention.

Paediatric antiretroviral therapy audit in South London.

To audit clinical and surrogate marker outcome data following the introduction of combination antiretroviral therapy to HIV-infected children in South London. We performed a retrospective cohort study of 110 HIV-infected children under the care of the Paediatric HIV in South London Network (PHILS-NET) from January 1996 to September 1999. The following were identified: type of antiretroviral therapy used; duration of therapy; toxicity; impact on viral load and CD4 count; reasons for changing therapy; and clinical progression. Ninety-one (83%) of the 110 children (55 females; median age 6.3 years) received 166 antiretroviral therapy regimens. Sixty per cent of the regimens were triple therapy: either two nucleoside reverse transcriptase inhibitors (NRTIs) and one protease inhibitor (58; 34.9%) or two NRTIs and one non-nucleoside reverse transcriptase inhibitor (39; 23.5%). The mean duration of completed therapy was 46 weeks for first line therapy with a standard deviation (SD) of 38 weeks and 40 weeks in third line therapy with an SD of 22 weeks. Changes in antiretroviral regimens were owing to virological failure in 60% and toxicity in 10%. Overall, 46% of children on first line and 37% on second line antiretroviral therapy achieved an undetectable viral load of < 400 HIV-1 RNA copies/mL. Clinical progression for the whole cohort fell from 3.7% per year for children on dual therapy to 0.7% per year for children on highly active antiretroviral therapy. This audit shows the clinical benefit of antiretroviral therapy use in a cohort of children with moderately advanced HIV disease. The surrogate outcome data seen for the viral load and CD4 count are similar to those of reports from clinical trials. Antiretroviral therapy regimens were sequenced rapidly, mainly owing to virological failure.

HIV‐Associated Disorders in Fat Distribution and Lipid Metabolism

AbstractHIV‐associated lipodystrophy is most commonly characterized by fat redistribution and/or metabolic changes, such as reduced lipid metabolism or impaired glucose tolerance. Despite the growing recognition of this disorder, its causes, characteristics, consequences, and optimal treatment are not fully understood. This review examines the current understanding of the etiology of this syndrome, its acute and long‐term implications for affected HIV‐infected patients, and treatment strategies currently under investigation, including changes in antiretroviral regimens, and the use of insulin‐sensitizing agents, growth hormones, and exercise regimens.

Prognostic value of combined response markers among human immunodeficiency virus-infected persons: possible aid in the decision to change zidovudine monotherapy.

To clarify useful clinical parameters for determining the need for changes in antiretroviral regimens, 586 persons who were seropositive for the human immunodeficiency virus (HIV) and who had intermediate-stage HIV disease underwent follow-up semiannually for a median of 3.1 years after zidovudine monotherapy was instituted. The strongest predictors of time to the development of AIDS and of survival were an increased CD4 lymphocyte count (> 50/microL), a decreased neopterin level (> 2.4 nmol/L), and no increase in the number of symptoms after 7-12 months of zidovudine therapy. Men who had the best quartile CD4 lymphocyte and neopterin responses and who also had no increase in the number of symptoms were 23 times less likely to die (reflecting a 96% increase in survival) than were men who had the worst responses in these variable categories. After 7-12 months of zidovudine therapy, 5-year survival rates were 63% for men with good responses in all three variable categories, 47%-49% for those with good CD4 lymphocyte responses and good responses in one other variable category, 31% for those with only a good CD4 lymphocyte response, and 0 for those with poor responses in all three variable categories.