Initial Highly Active Antiretroviral Therapy Regimen Research Articles

Excess mortality and associated factors among people living with HIV initiating highly active antiretroviral therapy in Luzhou, China 2006–2020

BackgroundTo estimate crude mortality, excess mortality, and standardized mortality rates (SMR) among people living with HIV (PLHIV) initiating highly active antiretroviral therapy (HAART) in Luzhou, China 2006–2020, and assess associated factors.MethodsPLHIV initiating HAART in the HIV/AIDS Comprehensive Response Information Management System (CRIMS) in Luzhou, China 2006–2020 were included in the retrospective cohort study. The crude mortality, excess mortality, and SMR were estimated. Multivariable Poisson regression model was used for analyzing risk factors associated with excess mortality rates.ResultsThe median age among 11,468 PLHIV initiating HAART was 54.5 years (IQR:43.1–65.2). The excess mortality rate decreased from 1.8 deaths/100 person-years (95% confidence interval [CI]:1.4–2.4) in 2006–2011 to 0.8 deaths/100 person-years (95%CI:0.7–0.9) in 2016–2020. SMR decreased from 5.4 deaths/100 person-years (95%CI:4.3–6.8) to 1.7 deaths/100 person-years (95%CI:1.5–1.8). Males had greater excess mortality with the eHR of 1.6 (95%CI:1.2–2.1) than females. PLHIV with CD4 counts ≥ 500 cells/μL had the eHR of 0.3 (95%CI:0.2–0.5) in comparison to those with CD4 counts < 200 cells/μL. PLHIV with WHO clinical stages III/IV had greater excess mortality with the eHR of 1.4 (95%CI:1.1–1.8). PLHIV with time from diagnosis to HAART initiation ≤ 3 months had the eHR of 0.7 (95%CI:0.5–0.9) compared to those with time ≥ 12 months. PLHIV with initial HAART regimens unchanged and viral suppression had the eHR of 1.9 (95%CI:1.4–2.6) and 0.1 (95%CI:0.0–0.1), respectively.ConclusionsThe excess mortality and SMR among PLHIV initiating HAART in Luzhou, China decreased substantially from 2006 to 2020, but the mortality rate among PLHIV was still higher than general population. PLHIV who were male, with baseline CD4 counts less than 200 cells/μL, WHO clinical stages III/IV, time from diagnosis to HAART initiation ≥ 12 months, initial HAART regimens unchanged, and virological failure had a greater risk of excess deaths. Early and efficient HAART would be significant in reducing excess mortality among PLHIV.

Magnitude and predictors of first-line antiretroviral therapy regimen change among HIV infected adults: A retrospective cross sectional study

BackgroundRegimen change remains a significant challenge towards the achievement of human immunodeficiency virus (HIV) treatment success. In developing countries where limited treatment options are available, strategies are required to ensure the sustainability and durability of the starting regimens. Nevertheless, information regarding the rate and predictors of regimen change is limited in these settings. ObjectiveThis study was undertaken to determine the prevalence and predictors of changes in ART regimens among patients initiating highly active antiretroviral therapy (HAART) at XX. Materials and methodsAn institutional based retrospective cross-sectional study was conducted among adult naïve HIV patients who had initiated HAART at XX between 2010. Data were extracted by reviewing their medical charts using a pretested structured check-list. The Kaplan–Meier survival analyses were used to describe the probability of ARV regimen changes while Cox proportional hazard regression models were employed to identify the predictors of ARV regimen modifications. Data were analyzed using SPSS version 21 software, and statistical significant was deemed at p < 0.05. ResultsA total of 770 patients were enrolled in this study of these 165 (21.43%) had their ART regimen modified at least once. Drug toxicity was the main reason for regimen change followed by TB comorbidity, and treatment failure. Positive baseline TB symptoms (aHR = 1.63, p = 0.037), and Zidovudine based regimen (aHR = 1.76, p = 0.011) as compared to Stavudine based regimen were at higher risk of ART modification. Conversely, urban residence, baseline World Health organization (WHO) stage 2 as compared to WHO stage 1, baseline CD4 count ≥301 as compared to CD4 count ≤200 were at lower risk of ART modification. ConclusionThe rate of initial HAART regimen change was found to be high. Thus, less toxic and better tolerated HIV treatment options should be available and used more frequently. Moreover, early detection and initiation of ART by the government is highly demanded to maximize the benefit and reduce risk of ART modifications.

Modification of Initial Highly Active Antiretroviral Therapy (HAART) Regimen in Paediatric HIV Patients.

Background:Treatment options among Human Immunodeficiency Virus (HIV)-infected children are limited as only a few Highly Active Antiretroviral Therapy (HAART) are approved worldwide for paediatric use. Among children, frequent changes in HAART regimen can rapidly exhaust treatment options, and information addressing this issue is scarce.Objective:The aim of the study was to determine factors associated with the modification of initial HAART regimen modification among HIV-infected children.Method:A retrospective study was performed among HIV-infected children aged 18 and below, that received HAART for at least six months in a tertiary hospital in Malaysia. Factors associated with modification of initial HAART regimen were investigated.Results:Out of 99 patients, 71.1% (n=71) required initial HAART regime modification. The most common reason for HAART modification was treatment failure (n=39, 54.9%). Other reasons included drug toxicity (n=14, 19.7%), change to fixed-dose products (n=11, 15.5%), product discontinuation (n=4, 5.6%) and intolerable taste (n=3, 4.2%). The overall mean time retention on initial HAART before regimen modification was 3.32 year ± 2.24 years (95% CI, 2.79–3.85). Patient's adherence was the only factor associated with initial regimen modification in this study. Participants with poor adherence showed a five-fold risk of having their initial HAART regimen modified compared to those with good adherence (adjusted OR [95% CI], 5.250 [1.614 – 17.076], p = 0.006).Conclusion:Poor adherence was significantly associated with initial regimen modification, intervention to improve patient's adherence is necessary to prevent multiple regimen modification among HIV-infected children.

The reasons for regimen shift among people living with HIV/AIDS in Asella Referral Hospital

Highly active antiretroviral therapy (HAART) is the base for management of patients with HIV infection. On the other hand, a switch in the antiretroviral regimen could be compulsory because of various reasons. Therefore, the aim of this study was to determine the causes for initial antiretroviral regimen switch among adult HIV/ADIS patients. A retrospective cross-sectional study was conducted on patient information records of those visited the ART clinic since February 2013 to January 2015 in Asella Referral Hospital. Results: From 1468 patientsÂ’ medical information reviewed, 221 of them changed their initial HAART regimens. Among these patients, 38% of them changed their first medications as a consequence of drug toxicity which was mainly triggered by AZT/3TC/NVP. The major cause for changing AZT/3TC/NVP treatment regimen associated with drug toxicity was anemia (17.85%). Other reasons stated for medication shift were co-morbidity, treatment failure, poor adherence and pregnancy. Since most of regimen modifications were in consequence of drug toxicity, these medication shifts require careful patient follow up; frequent laboratory result monitoring and selection of the right antiretroviral regimens.

Pharmacogenetic Associations with ADME Variants and Virologic Response to an Initial HAART Regimen in HIV-Infected Women.

BackgroundClinical response to highly active antiretroviral therapy (HAART) varies among different populations. A portion of this variability may be due to variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of HAART.DesignTo identify genetic factors involved in virologic responses to HAART, 13 genes in ADME pathways were analyzed in a cohort of HIV-infected women on HAART. A total of 569 HIV-positive participants from the Women’s Interagency HIV Study who initiated HAART from 1994–2012 and had genotype data were included in these analyses.MethodsAdmixture maximum likelihood burden testing was used to evaluate gene-level associations between common genetic variation and virologic response (achieving <80 viral copies/mL) to HAART overall and with specific drug classes. Results: Six statistically significant (P<0.05) gene-level burden tests were observed with response to specific regimen types. CYP2B6, CYP2C19 and CYP2C9 were significantly associated with response to protease inhibitor (PI)-based regimens. CYP2C9, ADH1A and UGT1A1 were significantly associated with response to triple nucleoside reverse transcriptase inhibitor (NRTI) treatment.ConclusionsAlthough no genome-wide associations with virologic response to HAART overall were detected in this cohort of HIV-infected women, more statistically significant gene-level burden tests were observed than would be expected by chance (two and a half expected, six observed). It is likely that variation in one of the significant genes is associated with virologic response to certain HAART regimens. Further characterization of the genes associated with response to PI-based treatment is warranted.

Rate of initial highly active anti-retroviral therapy regimen change and its predictors among adult HIV patients at University of Gondar Referral Hospital, Northwest Ethiopia: a retrospective follow up study.

BackgroundRegimen change is a major challenge for the sustainability of human immunodeficiency virus (HIV) treatment program. In a resource limited setting where treatment options are limited, designing strategies to increase the durability of original regimen are essential. However, information’s on rate of initial regimen change and its predictors is scarce in Ethiopia. Therefore, the purpose of this study was to assess the rate of initial highly active anti retroviral therapy (HAART) regimen change and its predictors among adult HIV patients at the University of Gondar Referral Hospital, Northwest Ethiopia.MethodsAn institutional based retrospective follow up study was conducted among 410 adult HIV patients started HAART from January 2010 to December 2014. Simple random sampling technique was used to select patient records using computer generated random number. Data were collected from patient chart using data extraction tool. The Kaplan–Meier curve was used to estimate the median duration of regimen change. Life table was used to estimate the cumulative survival for initial regimen change and log rank test to compare regimen change survival curves between the different categories of explanatory variables. Bivariate and multivariate Cox proportional hazard model were used to identify predictors of initial regimen change.ResultsThe overall incidence rate of initial regimen change was 10.11 (95 % CI 8.29, 12.6) per 100 person years (PY). Baseline WHO clinical stage III (AHR = 1.92, 95 % CI 1.12–3.35), occurrence of tuberculosis (TB) on the initial regimen (AHR = 8.33, 95 % CI 4.47–15.53), side effect on the initial regimen (AHR = 25.27, 95 % CI 15.12–42.00) and co-medication with ART (AHR = 2.5, 95 % CI 1.46–4.34) were significant predictors of initial regimen change.ConclusionsThe rate of initial HAART regimen change was found to be high. Having WHO clinical stage III, co-medication with ART, occurrence of tuberculosis and side effect on initial regimen were independent predictors of regimen change. Hence, close follow-up and screening of patient for side effect and tuberculosis is important.

A study of the adverse effects of antiretroviral therapy for HIV infection

Abstract Background The introduction of highly active antiretroviral therapy (HAART) has led to significant reduction in acquired immune deficiency syndrome (AIDS)-related morbidity and mortality. Unfortunately, up to 25% of patients discontinue their initial HAART regimen because of treatment failure, toxic effects or noncompliance within the first few months of therapy. Aims To assess adverse effects of antiretroviral therapy and its adherence in HIV infected patients in a resource-restricted setting in India. Methods A group of 400 HIV infected patients, attending class-A ART clinic attached to tertiary care hospital in Mumbai, was studied retrospectively over the period of one year from the initiation of ART to observe and assess adverse effects of ART. Data was obtained from patient treatment record sheet after due permission from ART officer. Results Most common adverse effect was Anemia(17.5%). Baseline CD4 count of less than or equal to 200cells/mm 3 was found to be significantly associated with the incidence of adverse effects ( p value Conclusion As HAART is only option for HIV/AIDS till date; to optimize adherence and thus, efficacy of ART, clinicians must focus on preventing adverse effects whenever possible, promoting the early recognition and reversal of potentially serious adverse effects, and reducing the potential for adverse drug interactions.

Increases in Duration of First Highly Active Antiretroviral Therapy Over Time (1996–2009) and Associated Factors in the Multicenter AIDS Cohort Study

Antiretroviral therapy (ART) regimens changes occur frequently among HIV-infected persons. Duration and type of initial highly active antiretroviral therapy (HAART) and factors associated with regimen switching were evaluated in the Multicenter AIDS Cohort Study. Participants were classified according to the calendar period of HAART initiation: T1 (1996-2001), T2 (2002-2005), and T3 (2006-2009). Kaplan-Meier curves depicted time from HAART initiation to first regimen changes within 5.5 years. Cox proportional hazards regression models were used to examine factors associated with time to switching. Of 1009 participants, 796 changed regimen within 5.5 years after HAART initiation. The percentage of participants who switched declined from 85% during T1 to 49% in T3. The likelihood of switching in T3 decreased by 50% (P < 0.01) compared with T1 after adjustment for pre-HAART ART use, age, race, and CD4 count. Incomplete HIV suppression decreased over time (P < 0.01) but predicted switching across all time periods. Lower HAART adherence (≤95% of prescribed doses) was predictive of switching only in T1. In T2, central nervous system symptoms predicted switching [relative hazard (RH) = 1.7; P = 0.012]. Older age at HAART initiation was associated with increased switching in T1 (RH = 1.03 per year increase) and decreased switching in T2 (RH = 0.97 per year increase). During the first 15 years of the HAART era, initial HAART regimen duration lengthened and regimen discontinuation rates diminished. Both HIV RNA nonsuppression and poor adherence predicted switching before 2001 while side effects that were possibly ART related were more prominent during T2.

Effects of pill burden on discontinuation of the initial HAART regimen in minority female patients prescribed 1 pill/day versus any other pill burden

Highly active antiretroviral therapy (HAART) is a mainstay of treatment for patients with Human Immunodeficiency Virus (HIV). Since second line HAART therapies can be costlier and less effective, it is essential to understand the duration of initial HAART therapies. The overall aim of this study was to estimate the effects of daily pill burden on the time to discontinuation of the initial HAART regimen. Patients were initially identified through the clinic's CAREWARE database. A chart review was conducted for data collection, where only adult, female, HIV-positive patients initiating therapy at the study clinic between 1 January 2001 and 31 December 2011 were included. All study subjects were followed up from the initiation of HAART to treatment discontinuation. A Kaplan–Meier curve was generated to describe time to discontinuation by regimens, and a Cox proportional hazards model was developed to assess the impact of different regimen and patient demographic characteristics on the hazard of discontinuation of the initial regimen. A total of 498 charts were initially reviewed. After assessment of these patients for inclusion criteria, a cohort of 115 adult female patients who initiated HAART at the study clinic was included. Patients treated with 1 pill/day regimen had a significantly longer time to discontinuation than regimens of >1 pills/day (mean duration of initial therapy was 1062.56 days vs. 631.70 days, respectively, p = 0.003). Compared to 1 pill/day regimens, >1 pills/day regimens were associated with a higher hazard of discontinuation (hazard ratio (HR) =3.44 with 95% confidence interval (CI) = 1.25, 9.48). A higher viral load and patients without insurance were also found to be significantly associated with increased hazards of discontinuation. Overall, female HIV patients initiating therapy with the 1 pill/day HAART regimen were less likely to discontinue their treatment compared to patients initiating with >1 pills/day HAART regimen.

HIV Drug Resistance and Its Impact on Antiretroviral Therapy in Chinese HIV-Infected Patients

BackgroundHighly active antiretroviral therapy (HAART) has significantly decreased mortality among Chinese HIV patients. However, emerging HIV drug resistance (HIVDR) poses a growing threat to the long-term success and durability of HAART.MethodsThree cross-sectional surveys were conducted across the country from 2004 to 2006, respectively. Patients completed a questionnaire and provided blood for CD4 cell count, HIV viral load (VL), and HIV resistance genotyping. Factors associated with HIVDR were identified by logistic regression.Results3667 unique patients were included across the three surveys. Among 2826 treatment-experienced patients, median duration of treatment was 17.4 (IQR 8.6–28.4) months and HIVDR was identified in 543 (19.2%). Factors significantly associated with HIVDR included ART drug distribution location, CD4 cell count, initial HAART regimen, self-reported medication adherence, and province.ConclusionsVirologic failure increased over time on therapy but a significant proportion of patients in failure had no resistance mutations identified, suggesting that treatment adherence is suboptimal and must be emphasized. Due to the significantly higher risk of HIVDR in certain provinces, additional steps to reduce HIVDR should be taken.

The reason for regimen change among HIV/AIDS patients initiated on first line highly active antiretroviral therapy in Southern Ethiopia

Background:Highly active antiretroviral therapy (HAART) has markedly decreased the morbidity and mortality due to HIV disease. However, toxicities, comorbidity, pregnancy, and treatment failure, among others, would result in frequent initial HAART regimen change.Aim:The study was designed to assess the causes of initial highly active antiretroviral therapeutic regimen changes among patients on HAART.Materials and Methods:The study was conducted using a retrospective institution-based study, by reviewing the patient information sheet and physician diagnosis cards. Patient cards that showed a change in the initial treatment regimen were assessed and analyzed, to identify the common reason that resulted in a change from the initial treatment regimen. The data was analyzed using SPSS version 16.0.Results:A total of 340 patient cards were assessed. The majority of the patients (69.29%) were females. The most common first regimen, before the first switch, was stavudine / lamivudine / nevirapine (D4T/3TC/NVP) (54.70%) and stavudine / lamivudine / Efavirenz (D4T/3TC/EFV) (20.88%). The main reasons for modification were toxicity, comorbidity, pregnancy, and treatment failure. The main types of toxicities observed were peripheral neuropathy (36.52%), rash (17.83%), and anemia (17.39%).Conclusion:Toxicity was the main reason for the modification of initial HAART among the study population. Efavirenz-based regimens had the lowest hazard for change relatively, except in pregnancy-related cases.

The outcome and choice of initial combination anti-retroviral therapy in treatment-naïve HIV-infected individuals

Background : Optimization of initial highly active antiretroviral therapy (HAART) for complete viral suppression and better tolerability is paramount for the prognosis of HIV-infected patients. Durable suppression of HIV therefore depends on the use of potent, well-tolerated antiretroviral regimens to which patients can easily adhere. The aim is to determine the outcome and factors influencing the choice of initial combination antiretroviral drugs in the treatment-naive HIV patients. Methods : The outcome and factors influencing the choice of initial antiretroviral drugs were investigated in HIV-infected treatment-naive individuals in a large HIV treatment clinic in south-western Nigeria using a cross-sectional design between January to December 2010. Results : 432 patients were analyzed (mean age 38 years ± 9.010), 67.6% females, 50.1% prior AIDS. Mean CD4 cells and HIV RNA were 146 cells/mm 3 and 194312 copies/ml respectively. Zidovudine-lamivudine-nevirapine regimen (ZDV-3TC-NVP) was prescribed in 34.3%, followed by tenofovir-emtricitabine-efavirenz (TDF-FTC-EFV) 26.9%, TDF-FTC-NVP (17.6%), TDF-3TC-NVP (8%), ZDV-3TC-EFV (4.6%), abacavir (ABC)-3TC-EFV (3.7%), ABC-3TC-NVP (2.8%). Difference in prescription was noted among the doctors. Compared with TDF-3TC-NVP, starting TDF-FTC-EFV was mainly associated in multivariate analysis with reduced pill burden (P 200,000 copies/ml (P=0.0015). TDF-3TC-NVP and TDF-3TC-ZDV-atazanavir (ATV)-ritonavir (RTV) were more likely in patients with drug substitution and switch programs respectively (P<0.001; P<0.001). ABC-3TC-EFV was more likely in patients with deranged creatinine levels (P=0.002). At 6 months and 12 months, 364 (84.3%) and 392 (90.7%) achieved virologic suppression respectively (HIV RNA copies <200 copies/ml). CD4 cells increased by 138 cells/mm 3 and 198 cells/mm 3 at 6 months and 12 months respectively. Virologic suppression was more likely with TDF-FTC-EFV (93.7%) while CD4 cells increase was higher with ZDV-3TC-NVP. The 2 most common often prescribed regimens, TDF-FTC-EFV and ZDV-3TC-NVP, had virologic response rates of 93.7% and 84.2% (P<0.001). Conclusion : Factors such as physician preference and patient-reported features play a role in the choice of initial HAART regimen. Identification of these features and simplification of treatment regimens will be necessary in order to maximize the effectiveness of HAART regimens.

Incidence and risk factors associated with lost to follow-up in a Belgian cohort of HIV-infected patients treated with highly active antiretroviral therapy

Being lost to follow-up (LTFU) is a major problem in caring for persons with HIV infection. We describe the proportions and characteristics of LTFU in a Belgian outpatient HIV clinic. All patients treated with highly active antiretroviral therapy (HAART) who attended at least two consultations were included. Patients not returning within the following year were considered LTFU. Multivariate analysis using logistic regression was performed. The LTFU rate was 5.5% on average and remained stable over the years. Patients LTFU were more often intravenous drug users (odds ratio [OR] = 3.48), not covered by health insurance (OR = 6.69), living outside the province (OR = 1.49) and treated with a complex initial HAART regimen (OR = 5.80). Increased age was also associated with a higher risk of LTFU. Patients at risk for LTFU after starting HAART should be the targeted for reinforced counselling and HIV treatment centres should establish systems to trace patients LTFU.

Impact of injecting drug use on response to highly active antiretroviral treatment in HIV-1-infected patients: A nationwide population-based cohort study

The objective of this study was to determine the effect of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients infected through injecting drug use (injecting drug users, IDUs) compared to patients infected via other routes (non-IDUs). We conducted a nationwide population-based cohort study of all HIV-infected patients who initiated HAART during the study period of 1 January 1995 to 31 December 2007. We compared changes in CD4(+) cell counts, percentage of full viral suppression (< 500 copies/ml) and mortality from start of HAART, as well as differences in initial HAART regimen. Three thousand six hundred and fifteen patients were included in the study, representing 22,804 person-y of observation. A total of 346 (9.6%) were categorized as IDUs. Of IDUs, 55% gained full viral control within the first y after HAART compared to 76% of non-IDUs (p = 0.0002). Absolute CD4(+) cell count and survival were lower for IDUs compared to non-IDUs (adjusted mortality rate ratio 3.6 (95% CI 2.9-4.3)). IDUs were more likely to receive a first regimen based on protease inhibitors (PIs) compared to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens for non-IDUs, and IDUs initiated HAART later than non-IDUs. In conclusion, more than half of the HIV-infected patients in Denmark infected through injecting drug use gained full viral suppression after initiating HAART. Absolute CD4(+) cell count was lower and mortality higher among IDUs than non-IDUs.

Associations With Virologic Treatment Failure in Adults on Antiretroviral Therapy in South Africa

Highly active antiretroviral therapy (HAART) has been available in government facilities in the Western Cape Province of South Africa since 2001. We aimed to investigate factors associated with virologic treatment failure in this setting. Case-control study, matched on facility and on starting date and duration of HAART. Cases and controls were identified from clinic registers from May 2001 to June 2006. Cases were patients who switched to second-line therapy after confirmed virologic failure (2 consecutive viral loads above 1000 copies/mL). Controls were on first-line treatment with viral load <400 copies per milliliter at the time of case incidence. One hundred thirty cases and 238 controls were selected from 8 clinics (median 16.6 months on HAART, interquartile range: 12.2-24.6). Treatment interruptions [adjusted odds ratio (AOR) 8.6, 95% confidence interval: 3.6 to 20.8], prior nevirapine-based prevention of mother-to-child transmission (PMTCT) treatment (AOR: 9.6, 95% confidence interval: 2.9 to 32.2), a baseline CD4 count less than 50 cells per microliter or from 50-150 cells per microliter (AOR: 6.6, 95% confidence interval: 2.3 to 18.8 and AOR: 5.8, 95% confidence interval: 2.1 to 16.3 compared with a baseline CD4 count of more than 150 cells/microL), and the use of nevirapine in the initial regimen (AOR: 2.5, 95% confidence interval: 1.4 to 4.7) were all independently associated with virologic treatment failure. In this setting, nevirapine in the initial HAART regimen or for PMTCT treatment is associated with virologic treatment failure, together with low CD4 count at ART initiation. Earlier initiation of HAART and access to improved triple therapy and PMTCT regimens are priorities for HIV programs in Southern Africa.

The Impact of Transmitted Drug-Resistance on Treatment Selection and Outcome of First-Line Highly Active Antiretroviral Therapy (HAART)

The study aim was to determine how resistance testing influences outcome of first-line highly active antiretroviral therapy (HAART) in routine practice in the United Kingdom. The prevalence of transmitted drug resistance and the genotypic sensitivity score (GSS) of first-line HAART regimens were determined using data from the UK Collaborative HIV Cohort(CHIC) Study. Factors associated with starting a regimen with a reduced GSS and subsequent virological responses were analyzed by logistic and Cox regression. Amongst patients tested in 1999–2006, 116 of 1175 (10%) had $1 resistance mutation; 64 patients (5.4%) had $1 mutation associated with resistance to drugs in the initial HAART regimen and 54 (4.6%) showed a GSS, 3. Factors independently associated with a GSS, 3 were starting HAART in 1999–2001 vs. 2004–2006 (odds ratio = 2.63; 95% confidence interval: 1.19 to 5.83) and use of ritonavir-boosted protease inhibitor (PI/r)–based vs. nonnucleoside reverse transcriptase inhibitor–based regimens (1.97; 1.06 to 3.64). AGSS .3 was independently associated with virological suppression(hazard ratio for GSS, 3 = 0.60; 95% confidence interval 0.41 to 0.87). Most patients starting HAART after undergoing resistance testing received regimens with a GSS $3. PI/r-based therapy was often selected in patients with resistance to the nucleoside reverse transcriptase inhibitor backbone. Low GSS predicted poor virological suppression and the association persisted after adjusting for PI/r use.

C-C2-03: Incidence-based Costs of Multiple HAART Switches Among HIV-infected Patients in an HMO

Background: Highly active antiretroviral therapy (HAART) or combination antiretroviral (ARV) therapy is associated with reduced morbidity and mortality. Yet, many HIV-infected patients endure incomplete HIV suppression from HAART or combination ARV therapy, increasing cost and limiting effectiveness. Little is known about the direct healthcare costs of HIV+ patients requiring multiple HAART regimen switches because of incomplete HIV suppression. In an HMO-based population of HIV+ patients, we examined resource and cost implications of multiple relative to single (or no) HAART switches starting from first HAART regimen. Methods: Retrospective analysis of HIV+ patients of the Northern California and Northwest regions of Kaiser Permanente during 2004. Continuous active 12-month membership and minimum 12 months of continuous HAART. Cases on third or later HAART regimen; controls on 1st or 2nd regimen. Regimen switch is combination change of two or more additions of ARV drugs to an existing HAART regimen. Cost categories drugs, outpatient, inpatient, lab, and radiology. Patients followed from first HAART regimen to death, disenrollment, or end of study up to 60 months. Results: 287 cases (19% female); 1,645 controls (12% female) followed from 1st regimen. Mean total per-patient follow-up costs were $105,132 (cases) vs. $70,004 (controls). Mean pharmacy costs were $70,672 (cases) vs. $49,668 (controls) (P <.04). Of cases mean pharmacy costs, 85% were antiretroviral-based (90% for controls). Mean dispenses of both ARV and non-ARV drugs were higher for cases (80 vs. 60 for antiretrovirals, 64 vs. 60 for non-antiretrovirals). Mean outpatient costs were $13,100 (cases) vs. $8,952 (controls) (P<.0001). Mean ER and mean non-specialty visits were both higher among cases (P <.03). Fourteen percent of cases had at least one inpatient stay vs. 10% of controls. Inpatient costs per patient with at least one stay were $101,396 (cases) vs. $72,000 (controls) (not significant). Mean radiology costs were $1,412 (cases) vs. $956 (controls) (P=.05); mean lab costs were $4,728 (cases) vs. $3,472 (controls) (P<.0001). Conclusions: HIV-infected patients on a third or later HAART regimen incurred costs in total and across most categories that greatly exceeded costs of similar patients on earlier regimens. Working to ensure success with initial HAART regimens appears to lower total cost of HIV care.

Raltegravir-Based HAART Regimen in a Patient with Large B-Cell Lymphoma

To describe the antiretroviral management of a patient diagnosed simultaneously with HIV/AIDS and diffuse large B-cell lymphoma, focusing on the drug-drug interactions between highly active antiretroviral therapy (HAART) and concomitant cancer chemotherapy. A 55-year-old white man was recently diagnosed with HIV/AIDS and presented 1 month later with complaints of nausea, vomiting, abdominal pain, double vision, right eye discomfort/swelling, and a 3.6-kg weight loss. An excisional biopsy of a right inguinal lymph node confirmed a new diagnosis of diffuse large B-cell lymphoma. HAART and a chemotherapeutic regimen, including cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with intrathecal methotrexate, was to be initiated. As the potential for multiple drug-drug interactions existed, raltegravir, abacavir, and lamivudine were chosen for the initial HAART regimen. The patient achieved and maintained an undetectable viral load throughout 6 CHOP cycles. HAART improves the chemotherapeutic response in patients with HIV and lymphoma. Multiple drug-drug interactions are possible in patients who are to receive CHOP and HAART. Cyclophosphamide and vincristine are metabolized via the CYP3A4 isoenzyme. Protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors both inhibit and induce CYP3A4, with the potential for altered chemotherapeutic and cytotoxic effects. When PIs are combined with CHOP, mortality is reduced, but increased adverse effects are demonstrated. Raltegravir, an integrase inhibitor, is eliminated via glucuronidation and results in minimal drug-drug interactions. Raltegravir improves virologic and immunologic responses in HAART-naïve patients and thus would be a suitable alternative for preventing chemotherapeutic-HAART interactions. There is limited information published regarding the potential for interactions between HAART and cancer chemotherapy. While further research is necessary, it is important for clinicians to consider the potential for drug-drug interactions when designing a HAART regimen concurrently with chemotherapy.

A novel use of AIDS surveillance data to assess the impact of initial treatment regimen on survival

The expense in time and money limit the use of randomized clinical trials (RCT) and cohort studies for evaluating long-term AIDS treatment outcomes. We conducted a case-control study to characterize predictors of AIDS mortality after the availability of highly active antiretroviral therapy (HAART) in San Francisco, in which cases were matched with controls on stage of disease, year of AIDS diagnosis and year of HAART initiation. Overall, 266 cases and 1173 controls were included, representing >90% of eligible patients. The class of initial HAART regimen was not associated with mortality. Predictors of mortality were older age ([adjusted odds ratio] AOR 1.23, 95% [confidence interval] CI: 1.13-1.35), public versus private health insurance (AOR 2.80, 95% CI: 1.77-4.42), no versus private insurance (AOR 1.45, 95% CI: 1.02-2.07) and unboosted saquinavir (AOR 2.50, 95% CI: 1.34-4.65). Survival benefit was found in following the 2004 US Department of Health and Human Services preferred treatment guidelines; borderline survival benefits were found in following the guidelines from other years. Similar predictors were found for all-cause and AIDS-specific mortality. Our findings mirrored those of RCT and multi-centre cohort studies, and may be applicable to other settings. Our findings support similar survival benefit to persons initiating HAART with non-nucleoside reverse transcriptase inhibitor- or protease inhibitor-based regimens.

The associations between age and the development of laboratory abnormalities and treatment discontinuation for reasons other than virological failure in the first year of highly active antiretroviral therapy

The aim of this study was to describe the relationship between age and the time to treatment discontinuation in the absence of virological failure as well as the development of specific laboratory abnormalities, in patients starting highly active antiretroviral therapy (HAART) for the first time. Analyses included 8708 antiretroviral-naïve patients from the UK Collaborative HIV Cohort (CHIC) study who started HAART from 1998 onwards. We considered time to the first discontinuation of any drug in the initial HAART regimen for reasons other than virological failure; the association between this and age at the start of HAART was determined using proportional hazards regression after adjustment for potential confounders. The incidence of specific laboratory abnormalities in the first year after starting HAART was compared in those of different ages using multiple logistic regression. A total of 2650 patients discontinued at least one drug in their HAART regimen in the first year for reasons other than virological failure; after controlling for confounders, those aged < 30 years at the time of starting HAART were more likely to discontinue than those aged 30-39 years [relative hazard (RH) 1.12; 95% confidence interval (CI) 1.01, 1.24] as were those aged > or = 50 years (RH 1.14; 95% CI 1.00, 1.31). There were strong associations between greater age and raised total cholesterol, decreased haemoglobin and raised triglycerides over the first year, although the latter disappeared after adjustment for pre-HAART levels, suggesting that this finding reflected higher pre-HAART triglyceride levels in older individuals. Continued attempts to improve the tolerability of HAART regimens may help to sustain the good outcomes in all age groups over the longer term.