First-line Highly Active Antiretroviral Therapy Research Articles

The association of CD4 lymphocyte count with drug hypersensitivity reaction to highly active antiretroviral therapy, trimethoprim sulfamethoxazole, and antitubercular agents in human immunodeficiency virus patients.

BackgroundThe introduction of highly active antiretroviral therapy (HAART) and antibiotic regimens for the treatment of human immunodeficiency virus (HIV) and its concomitant opportunistic infections, respectively, significantly improve the morbidity and mortality of the infected patients. However, these drugs commonly cause drug hypersensitivity reactions (DHRs) in patients with acquired immunodeficiency syndrome. The reason proposed are multifactorial, which includes immune hyperactivation, changes in drug metabolism, patient cytokine profiles, oxidative stress, genetic predisposition, and the principal target in HIV patients, the CD4+ lymphocytes.ObjectiveThis study determined the association of CD4 count and DHRs to first-line HAART, trimethoprim sulfamethoxazole, and antitubercular agents among HIV patients.MethodsThis is a retrospective analytical study. Review of charts were done. The demographic and clinical profile used a descriptive statistics such as mean and standard deviation for quantitative data and frequency and percent for categorical data. Chi-square and Fisher exact tests were used to measure the degree of the relationship of CD4 count and DHRs.ResultsA total of 337 eligible patients were included. There was a 25% incidence of hypersensitivity reactions. However, the prevalence of DHRs across the different CD4 groups was not statistically significant (p = 0.167). Likewise, the study found no significant association between the CD4 count and DHRs to first-line HAART, trimethoprim sulfamethoxazole, and antitubercular agents (p = 0.311). The most common DHR was morbilliform rash, and nevirapine was the most reported antiretroviral drug causing DHR.ConclusionThere was no association in the CD4 count and DHRs to first-line HAART, trimethoprim sulfamethoxazole, and antitubercular agents. Hence, regardless of the baseline CD4 lymphocyte count, the physician should be vigilant in monitoring hypersensitivity reactions. Patient education on common DHRs is very important upon diagnosis of HIV and/or initiation of treatment.

Thyroid dysfunction in patients on antiretroviral therapy: A perspective from southern India.

Thyroid dysfunction in patients with human retroviral infection has been reported but the prevalence of thyroid function abnormalities in patients on highly active antiretroviral therapy (HAART) has not been studied. We aimed to assess the prevalence of thyroid dysfunction and autoimmunity (antithyroid peroxidase auto-antibodies [TPO-Ab]) in patients on first-line HAART, identify risk factors for thyroid dysfunction and determine any association of thyroid dysfunction with HAART. We screened and enrolled consecutive patients from the outpatient department if they were (i) diagnosed with HIV infection (enzyme-linked immunosorbent assay); (ii) aged more than 18 years; (iii) on HAART for 1 year or more; and (iv) clinically stable with no evidence of any acute illness in the past 2 months. We excluded patients who were on drugs that affect thyroid function. Thyroid function tests and CD4 counts were done. A total of 159 patients on firstline HAART were included in the study. Their mean (SD) age was 43.3 (10) years and duration of HAART was 44.4 (33.54) months. The mean CD4 count was 502.8 (274.45). Forty-seven patients (29.6%) had thyroid dysfunction. TPO-Ab positivity was noted in 6 patients. No association was seen between thyroid dysfunction and any type of regimen or drug. There was a significant negative correlation between CD4 counts and thyroid-stimulating harmone (TSH) suggesting that thyroid dysfunction may be more prevalent when immunity is low. There is a high prevalence of thyroid dysfunction, predominantly subclinical hypothyroidism, in patients on HAART. Thyroid autoimmunity is low in this subset of patients. Lower immunity is associated with higher TSH levels. Larger longitudinal studies are required to determine the course of hypothyroidism in patients on HAART.

Characterization of HIV-1 Near Full-Length Proviral Genome Quasispecies from Patients with Undetectable Viral Load Undergoing First-Line HAART Therapy.

Increased access to highly active antiretroviral therapy (HAART) by human immunodeficiency virus postive (HIV+) individuals has become a reality worldwide. In Brazil, HAART currently reaches over half of HIV-infected subjects. In the context of a remarkable HIV-1 genetic variability, highly related variants, called quasispecies, are generated. HIV quasispecies generated during infection can influence virus persistence and pathogenicity, representing a challenge to treatment. However, the clinical relevance of minority quasispecies is still uncertain. In this study, we have determined the archived proviral sequences, viral subtype and drug resistance mutations from a cohort of HIV+ patients with undetectable viral load undergoing HAART as first-line therapy using next-generation sequencing for near full-length virus genome (NFLG) assembly. HIV-1 consensus sequences representing NFLG were obtained for eleven patients, while for another twelve varying genome coverage rates were obtained. Phylogenetic analysis showed the predominance of subtype B (83%; 19/23). Considering the minority variants, 18 patients carried archived virus harboring at least one mutation conferring antiretroviral resistance; for six patients, the mutations correlated with the current ARVs used. These data highlight the importance of monitoring HIV minority drug resistant variants and their clinical impact, to guide future regimen switches and improve HIV treatment success.

Prevalence of Hypertension in HIV/AIDS Patients on Highly Active Antiretroviral Therapy (HAART) Compared with HAART-Naïve Patients at the Limbe Regional Hospital, Cameroon

BackgroundHighly active antiretroviral therapy (HAART) has greatly reduced the morbidity and mortality of HIV/AIDS patients but has also been associated with increased metabolic complications and cardiovascular diseases. Data on the association between HAART and hypertension (HTN) in Africa are scarce.ObjectivesPrimarily to compare the prevalence of HTN in HIV/AIDS patients on HAART and HAART-naïve patients in Limbe, Cameroon; and secondarily to assess other socio-demographic and clinical factors associated with HTN in this population.MethodsA cross-sectional study was conducted at the Limbe Regional Hospital HIV treatment center between April and June 2013, involving 200 HIV/AIDS patients (100 on first-line HAART regimens for at least 12 months matched by age and sex to 100 HAART-naïve patients). HTN was defined as a systolic blood pressure (BP) ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg.ResultsThe prevalence of HTN in patients on HAART was twice (38%; 95% CI: 28.5–48.3) that of the HAART-naïve patients (19%; 95% CI, 11.8–28.1), p = 0.003. In multivariate analyses adjusted for age, gender, smoking, family history of HTN, and BMI-defined overweight, HAART was associated with HTN, the adjusted odds ratio of the HAART-treated versus HAART-naïve group was 2.20 (95% CI: 1.07–4.52), p = 0.032. HTN was associated with older age and male gender, in the HAART group and with BMI-defined overweight in the HAART-naïve group.ConclusionThe prevalence of hypertension in HIV/AIDS patients in Limbe stands out to be elevated, higher in patients on HAART compared to those not on treatment. Blood pressure and cardiovascular risk factors should be routinely monitored. Other factors such as diet, weight control and physical exercise should also be considered.

Dysregulated Immune Activation in Second-Line HAART HIV+ Patients Is Similar to That of Untreated Patients.

BackgroundSuccessful highly active antiretroviral therapy (HAART) has changed the outcome of AIDS patients worldwide because the complete suppression of viremia improves health and prolongs life expectancy of HIV-1+ patients. However, little attention has been given to the immunological profile of patients under distinct HAART regimens. This work aimed to investigate the differences in the immunological pattern of HIV-1+ patients under the first- or second-line HAART in Brazil.MethodsCD4+ T cell counts, Viral load, and plasma concentration of sCD14, sCD163, MCP-1, RANTES, IP-10, IL-1β, IL-6, TNF-α, IL-12, IFN-α, IFN-γ, IL-4, IL-5, and IL-10 were assessed for immunological characterization of the following clinical groups: Non-infected individuals (NI; n = 66), HIV-1+ untreated (HIV; n = 46), HIV-1+ treated with first-line HAART (HAART 1; n = 15); and HIV-1+ treated with second-line HAART (HAART 2; n = 15).ResultsWe found that the immunological biosignature pattern of HAART 1 is similar to that of NI individuals, especially in patients presenting slow progression of the disease, while patients under HAART 2 remain in a moderate inflammatory state, which is similar to that of untreated HIV patients pattern. Network correlations revealed that differences in IP-10, TNF-α, IL-6, IFN-α, and IL-10 interactions were primordial in HIV disease and treatment. Heat map and decision tree analysis identified that IP-10>TNF-α>IFN-α were the best respective HAART segregation biomarkers.ConclusionHIV patients in different HAART regimens develop distinct immunological biosignature, introducing a novel perspective into disease outcome and potential new therapies that consider HAART patients as a heterogeneous group.

Association of Helicobacter pylori infection with the metabolic syndrome among HIV-infected black Africans receiving highly active antiretroviral therapy.

SummaryIntroductionThe metabolic syndrome (MetS) is common in human immune deficiency virus (HIV)-infected individuals receiving highly active antiretroviral therapy (HAART). Immune deficiencies caused by HIV give rise to numerous opportunistic gastrointestinal pathogens such as Helicobacter pylori, the commonest cause of chronic gastritis. The study sought to determine the relationship between H pylori infection and the MetS among HIV-infected clinic attendees.MethodsThis cross-sectional study was carried out in a specialised heart clinic in Kinshasa, DR Congo. Between January 2004 and December 2008, 116 HIV-infected patients (61 with MetS and 55 without MetS) who underwent upper gastrointestinal endoscopy for dyspeptic symptoms were included in the study following an informed consent. Univariate associations were determined by odds ratios (OR), while multivariate logistic regression analysis was used to identify factors associated with the MetS.ResultsH pylori infection (OR = 13.5, 95% CI: 10.3–17.6; p < 0.0001) and peripheral obesity (median hip circumference ≥ 97 cm) (OR = 4.7, 95% CI: 1.2–18.8; p = 0.029) were identified as MetS-related factors in HIV-infected patients. Higher rates of the MetS were associated with increased incidence of HIV-related immunocompromise using World Health Organisation (WHO) staging criteria. There was a univariate significant difference in the prevalence of the MetS between antiretroviral therapy (ART)-naïve patients and patients treated by means of a first-line HAART regimen of stavudine (d4T), lamivudine (3TC) and nevirapine (NVP). However, this difference was not significant in multivariate logistic analysis.ConclusionH pylori infection was significantly associated with the MetS in HIV-infected patients.

Safety and Effectiveness of Highly Active Antiretroviral Therapy in Treatment-Naïve HIV Patients: Preliminary Findings of a Cohort Event Monitoring Study in Belarus.

Antiretroviral drugs have well-documented evidence-based favorable benefit-risk ratios. Although various studies have investigated and characterized the safety profile of antiretroviral medicines, there are a limited number of studies evaluating the safety of first-line antiretroviral therapy (ART) in patients with a specific co-morbidity. A cohort event monitoring (CEM) study of the safety and effectiveness of antiretroviral medicines in a target population that has a significant level of co-morbidities (chronic infectious diseases, peripheral blood cytopenias) was implemented. The aim was to evaluate the safety profile of the highly active ART (HAART) in the target population and subpopulations with risk factors, to optimize the monitoring and decision-making procedure for subgroups of patients with specific types of co-morbidity, and to implement a more vigilant approach to therapy management in risk groups of patients. Prospective observational CEM was implemented among HAART-naïve HIV-positive patients at four clinical sites from December 2012. Eligible patients were those starting first-line HAART. Close medical supervision of all enrolled patients, with regular clinical and laboratory monitoring, was provided by healthcare professionals within 1 year after commencement of therapy. Standardized forms were used for data collection on initial and subsequent visits. All objective or subjective deviations in condition (events) were assessed for a causal relationship with ART, and for severity, seriousness, reversibility, preventability, and pre-existing risk factors in the case of adverse drug reactions (ADRs). A total of 518 HAART-naïve HIV-positive patients were enrolled in the CEM study. Of these patients, 65% (337) experienced one or several ADRs related to one or more components of HAART. Most of the ADRs reported were non-serious, expected, common (very common), transient (correctable), or reversible. The most common were hematotoxic, hepatotoxic, and neurotoxic adverse reactions. In several cases, some types of toxicities, associated with zidovudine, efavirenz, and nevirapine, had a high level of severity, necessitating hospitalization and drug regimen or single-agent substitution. Severe cases of hematological, hepatobiliary, and psychiatric toxicities were associated with pre-existing risk factors. CEM is an effective tool for safety and effectiveness monitoring and could be successfully implemented for intensive study of important safety issues and for overcoming knowledge gaps regarding safety. In order to achieve a favorable benefit-risk ratio for HAART in the specific sections of the population with pre-existing risk factors for development of ART toxicities, more vigilant consideration and careful assessment before therapy is commenced and further regular monitoring of key laboratory parameters is required.

Risk of first-line antiretroviral therapy failure in HIV-infected Thai children and adolescents.

Adolescence may affect adherence and response to highly active antiretroviral therapy (HAART). Limited data are available regarding the long-term treatment outcomes of perinatal HIV-infected adolescents. Data from perinatally acquired HIV-infected Thai children who started first-line nonnucleoside analog-based HAART before 18 years of age and treated for ≥24 weeks were analyzed. Children were categorized by age at HAART initiation; age<3 years, 3-9 years, early adolescence (10-13 years) and middle adolescence (14-16 years). CD4 and HIV-RNA were monitored every 6-12 months. Virologic failure (VF) was defined as HIV-RNA≥1000 copies/mL after ≥24 weeks of HAART. Of 840 children, 68% were in pre-adolescence. Median baseline CD4% was 7.9%. Use of nevirapine versus efavirenz was 77:23%. Median duration of nonnucleoside reverse transcriptase inhibitor-based HAART was 5.6 years. No differences between groups were observed for rate of HIV-RNA<50 copies/mL (68%, P=0.18) and rate of VF (28%, P=0.82), median time to VF (22 months, P=0.13). Incidence of VF per 100 child-year in children age<3 years, 3-9 years, early adolescence and middle adolescence were 7.9, 4.7, 7.4 and 10.8, respectively (P=0.012). Median adherence by pill count was 97.3% (P=0.23). By multivariate analysis, predictors for VF were age at HAART initiation of <3 years (HR: 1.73, 95% CI: 1.18-2.55), age 10-16 years (HR: 1.47, 95% CI: 1.09-1.97), and nevirapine use (HR: 1.63, 95% CI: 1.14-2.32). VF rates were observed in one-third of long-term treated Thai children on first-line HAART. Age 3-9 years at HAART initiation was associated with less VF compared with those younger or older, whereas children who used nevirapine had higher VF.

Emerging trends of HIV drug resistance in Chinese HIV-infected patients receiving first-line highly active antiretroviral therapy: a systematic review and meta-analysis.

Highly active antiretroviral therapy (HAART) has led to a dramatic decrease in AIDS-related morbidity and mortality through sustained suppression of human immunodeficiency virus (HIV) replication and reconstitution of the immune response. Settings like China that experienced rapid HAART rollout and relatively limited drug selection face considerable challenges in controlling HIV drug resistance (DR). We conducted a systematic review and meta-analysis to describe trends in emergent HIV DR to first-line HAART among Chinese HIV-infected patients, as reflected in the point prevalence of HIV DR at key points and fixed intervals after treatment initiation, using data from cohort studies and cross-sectional studies respectively. Pooled prevalence of HIV DR from longitudinal cohorts studies was 10.79% (95% confidence interval [CI], 5.85%-19.07%) after 12 months of HAART and 80.58% (95% CI, 76.6%-84.02%) after 72 months of HAART. The HIV DR prevalence from cross-sectional studies was measured in treatment intervals; during the 0-12-month HAART treatment interval, the pooled prevalence of HIV DR was 11.1% (95% CI, 7.49%-16.14%), which increased to 22.92% at 61-72 months (95% CI, 9.45%-45.86%). Stratified analyses showed that patients receiving a didanosine-based regimen had higher HIV DR prevalence than those not taking didanosine (15.82% vs 4.97%). Patients infected through former plasma donation and those receiving AIDS treatment at village clinics had higher HIV DR prevalence than those infected through sexual transmission or treated at a county-level hospital. Our findings indicate higher prevalence of HIV DR for patients with longer cumulative HAART exposure, highlighting important subgroups for future HIV DR surveillance and control.

Cost analysis of initial highly active antiretroviral therapy regimens for managing human immunodeficiency virus-infected patients according to clinical practice in a hospital setting

ObjectiveIn the study reported here, single-tablet regimen (STR) versus (vs) multi-tablet regimen (MTR) strategies were evaluated through a cost analysis in a large cohort of patients starting their first highly active antiretroviral therapy (HAART). Adult human immunodeficiency virus (HIV) 1-naïve patients, followed at the San Raffaele Hospital, Milan, Italy, starting their first-line regimen from June 2008 to April 2012 were included in the analysis.MethodsThe most frequently used first-line HAART regimens (>10%) were grouped into two classes: 1) STR of tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + efavirenz (EFV) and 2) MTR including TDF + FTC + EFV, TDF + FTC + atazanavir/ritonavir (ATV/r), TDF + FTC + darunavir/ritonavir (DRV/r), and TDF + FTC + lopinavir/ritoavir (LPV/r). Data were analyzed from the point of view of the Lombardy Regional Health Service. HAART, hospitalizations, visits, medical examinations, and other concomitant non-HAART drug costs were evaluated and price variations included. Descriptive statistics were calculated for baseline demographic, clinical, and laboratory characteristics; associations between categorical variables and type of antiretroviral strategy (STR vs MTR) were examined using chi-square or Fisher’s exact tests. At multivariate analysis, the generalized linear model was used to identify the predictive factors of the overall costs of the first-line HAART regimens.ResultsA total of 474 naïve patients (90% male, mean age 42.2 years, mean baseline HIV-RNA 4.50 log 10 copies/mL, and cluster of differentiation 4 [CD4+] count of 310 cells/μL, with a mean follow-up of 28 months) were included. Patients starting an STR treatment were less frequently antibody-hepatitis C virus positive (4% vs 11%, P=0.040), and had higher mean CD4+ values (351 vs 297 cells/μL, P=0.004) than MTR patients. The mean annual cost per patient in the STR group was €9,213.00 (range: €6,574.71–€33,570.00) and €14,277.00 (range: €5,908.89–€82,310.30) among MTR patients. At multivariate analysis, after adjustment for age, sex, antibody-hepatitis C virus status, HIV risk factors, baseline CD4+, and HIV-RNA, the cost analysis was significantly lower among patients starting an STR treatment than those starting an MTR (adjusted mean: €12,096.00 vs €16,106.00, P=0.0001).ConclusionSTR was associated with a lower annual cost per patient than MTR, thus can be considered a cost-saving strategy in the treatment of HIV patients. This analysis is an important tool for policy makers and health care professionals to make short- and long-term cost projections and thus assess the impact of these on available budgets.

HIV-1 coreceptor switch during 2 years of structured treatment interruptions

The purpose of this investigation was to determine the impact on human immunodeficiency virus (HIV) tropism of uncontrolled virus exposure during 2 years of intermittent highly active antiretroviral therapy (HAART). The Istituto Superiore di Sanità-Pulsed Antiretroviral Therapy (ISS-PART) randomized study compared the outcome of 2 years of structured treatment interruptions (STIs) versus standard continuous treatment in first-line HAART responder subjects. The STI schedule consisted of five STIs of 1, 1, 2, 2, and 3 months, respectively, separated by four periods of 3-month therapy. In the present study, coreceptor tropism was assessed in 12 patients of the STI arm at different time points over a period of 2 years. Tropism was determined on DNA and RNA by V3 loop region sequencing. The Geno2pheno algorithm (false-positive rate, FPR: 20%) was used for data interpretation. At baseline, 9/12 subjects (75.0%) had CCR5-tropic viruses in their HIV. Three had a CXCR4-tropic virus. Ten patients maintained the same coreceptor in DNA after 2 years, whereas in two patients, a shift occurred (one R5-X4, one X4-R5). In a patient with an R5 virus at baseline, a transient change to X4 tropism was seen in the rebounding virus during STI. Changes in tropism were not associated with the amplitude and duration of virus exposure during STIs, residual viremia at baseline, or the development of resistance mutations in the RT region. Our preliminary results suggest that viral replication, observed after short periods of treatment interruption, is not enough to drive the evolution of HIV tropism.

Hepatitis B virus in HIV-infected patients in north-eastern South Africa: Prevalence, exposure, protection and response to HAART

Hepatitis B virus (HBV) and HIV are endemic infections in many African countries. The objectives of this study were to determine the levels of exposure to, and protection from, HBV, as well as the prevalence of HIV/HBV co-infection and the response of HBV to highly active anti-retroviral therapy (HAART) in a cross-section of HIV-infected patients in north-eastern South Africa. This was a laboratory-based, unmatched study. Three hundred and eighty patients were screened by ELISA for HBsAg, anti-HBc and anti-HBs. Samples non-reactive for HBsAg but reactive for anti-HBc were examined for occult HBV infection. Response to HAART was assessed by measuring HBV viral loads, seroconversion from HBeAg to anti-HBe, and levels of aminotransferase. Of the study population of 380, 60% (95% CI 54.8 - 64.9) were exposed to HBV based on HBsAg, anti-HBs or anti-HBc; 20% (95% CI 16.1 - 24.4) had active HBV infection, based on HBsAg serology, and 30% (95% CI 25.2 - 35.2) were protected, based on anti-HBs levels > or = 10 IU/l. Of 181 HBsAg-negative individuals, 61 had HBV occult infection (33.7%, 95% CI 26.9 - 41.1). The differences in prevalence were not statistically significant when gender, marital status and CD4+ cell counts were considered. Of 21 patients analysed, 80% showed adequate response to the first-line HAART regimen (stavudine/lamivudine/efavirenz or nevirapine) after 12 months of use. The study confirms the higher level (60%) of exposure to HBV in HIV patients in Limpopo Province, as well as the high (20%) prevalence of HBsAg positivity and occult hepatitis B (33.7%). However, further studies are warranted to corroborate the benefit of lamivudine-containing HAART regimens, as HIV/HBV co-infected patients have a higher liver-related mortality if hepatitis B is not treated.

HIV-1 Drug Resistance and Associated Factors Among Adults Failing First-Line Highly Active Antiretroviral Therapy in Ho Chi Minh City, Vietnam

Background & Objectives: Little is known about HIV-1 drug resistance (HIVDR) in people failing first-line highly active antiretroviral therapy (HAART) in Vietnam. The aim of this study was to investigate the frequency of HIV-1 drug resistance mutations (DRMs) and determine correlates of acquiring genotypic HIVDR among Vietnamese adults (age ≥18) who met the immunological or clinical criteria of first-line HAART failure according to the guidelines of the World Health Organization (WHO). Methods: A total of 138 individuals participated in a descriptive study in Ho Chi Minh City between 2006 and 2009. Blood samples were collected for performing HIV-1 viral load (VL) and genotyping for specimens with VL ≥1,000 copies/mL. Stanford algorithm was used to interpret DRMs and multivariate analyses were performed to investigate predictors of HIVDR acquisition. Results: Of the study population, most participants failed either stavudine/lamivudine/nevirapine or stavudine/lamivudine/efavirenz (116 individuals). Up to 51 people obtained a VL <1,000 copies/mL. Among 87 participating individuals with VL ≥1,000 copies/mL, 11 people still harbored a wild-type strain, while 76 participants harbored a HIV-1 drug-resistant strain (2 of which were against protease inhibitors); common DRMs were M184I/V (74%), Y181I/C/V (39%), G190A/S (32%), T215Y/F (32%), and K103N (31%). The proportions of K65R, Q151M, and T69 insertion were 13%, 11%, and 5%, respectively. Being antiretroviral-exposed before initiating first-line HAART in a public and free-of-charge outpatient clinic, having nonadherence to first-line HAART, per 12-month increase of duration on first-line HAART, and having clinical failure criteria were significantly associated with a genotypic HIVDR acquisition. Conclusions: In the absence of VL for the population with WHO immunological/ clinical treatment failure criteria, a large proportion of people still achieved a VL <1,000 copies/mL, while a high prevalence of HIVDR was observed in those with VL ≥1,000 copies/mL. Thus, VL monitoring should be implemented now for the HAART-treated population in Vietnam.

Prevalence of dyslipidemia among HIV-infected patients using first-line highly active antiretroviral therapy in Southern Ethiopia: a cross-sectional comparative group study

BackgroundData on lipid profile abnormalities among patients receiving highly active antiretroviral treatment in Ethiopia are very limited. The aim of this study was to determine the prevalence of dyslipidemia and characteristics of lipid profiles among patients living with human immunodeficiency virus (HIV) using first-line highly active antiretroviral therapy (HAART) in Southern Ethiopia.MethodsThis cross sectional comparative group study was conducted between March and May 2012, and included 113 HIV infected patients treated for a minimum of one year with first-line HAART regimens that included Efavirenz and Nevirapine (HAART group) and others 113 who had never received HAART (pre-HAART group). Serum lipid profiles were determined after overnight fasting and dyslipidemia was assessed according to the United State National Cholesterol Education program-III guideline. For statistical analysis Chi-square, student’s t-test, and logistic regression were used using Statistical Package for Social Sciences (SPSS) Version 20.ResultNinety-three (82.3%) of HAART and 87 (76.9%) pre-HAART patients had at least one laboratory abnormality, which is compatible with a diagnosis of dyslipidemia. Total cholesterol ≥ 200 mg/dl occurred in 43.4% of HAART and 15.9% pre-HAART patients (p=<0.0001), whereas HDL-cholesterol below 40 mg/dl occurred in 43.4% and in 63.7% respectively, (p=0.002). The LDL-cholesterol ≥ 130 mg/dl occurred in 33.6% of HAART and 15% pre-HAART patients (p=0.001), while triglycerides ≥ 150 mg/dl occurred in 55.8% and 31.0% respectively, (p=0.001). Receiving of HAART was significantly and positively associated with raised total cholesterol, LDL-cholesterol, and triglycerides. The adjusted odds ratio (95% CI) of HAART-treated vs. pre-HAART was 3.80 (1.34-6.55) for total cholesterol ≥ 200 mg/dl; 2.64 (1.31-5.32) for LDL- cholesterol ≥ 130 mg/dl and 2.50 (1.41-4.42) for triglycerides ≥150 mg/dl.ConclusionUse of first-line antiretroviral therapy regimens that contain Efavirenz and Nevirapine were associated with raised total cholesterol, LDL-cholesterol, and triglycerides, an established atherogenic lipid profiles. Lipid profiles should be performed at baseline before commencement of antiretroviral therapy and then periodically through treatment follow-up to monitor any rising trends.

The cost effectiveness of home-based provision of antiretroviral therapy in rural Uganda.

Highly active antiretroviral therapy (HAART) provides dramatic health benefits for HIV-infected individuals in Africa, and widespread implementation of HAART is proceeding rapidly. Little is known about the cost and cost effectiveness of HAART programmes. To determine the incremental cost effectiveness of a home-based HAART programme in rural Uganda. A computer-based, deterministic cost-effectiveness model was used to assess a broad range of economic inputs and health outcomes. From the societal perspective, the cost effectiveness of HAART and cotrimoxazole prophylaxis was compared with cotrimoxazole alone, and with the period before either intervention. Data for 24 months were derived from a trial of home-based HAART in 1045 patients in the Tororo District in eastern Uganda. Costs and outcomes were projected out to 15 years. All costs are in year 2004 values. The main outcome measures were HAART programme costs, health benefits accruing to HAART recipients, averted HIV infections in adults and children and the resulting effects on medical care costs. The first-line HAART regimen consisted of standard doses of stavudine, lamivudine, and either nevirapine or, for patients with active tuberculosis, efavirenz. Second-line therapy consisted of tenofovir, didanosine and lopinavir/ritonavir. For children, first-line HAART consisted of zidovudine, lamivudine and nevirapine syrup; second-line therapy was stavudine, didanosine and lopinavir/ritonavir. The HAART programme, standardized for 1000 patients, cost an incremental $US1.39 million in its first 2 years. Compared with cotrimoxazole prophylaxis alone, the programme reduced mortality by 87%, and averted 6861 incremental disability-adjusted life-years (DALYs). Benefits were accrued from reduced mortality in HIV-infected adults (67.5% of all benefits), prevention of death in HIV-negative children (20.7%), averted HIV infections in adults (9.1%) and children (1.0%), and improved health status (1.7%). The net programme cost, including the medical cost implications of these health benefits, was $US4.10 million. The net cost per DALY averted was $US597 compared with cotrimoxazole alone. Many HIV interventions have a cost-effectiveness ratio in the range of $US1-150 per DALY averted. This study suggests that a home-based HAART programme in rural Africa may be more cost effective than most previous estimates for facility-based HAART programmes, but remains less cost effective than many HIV prevention and care interventions, including cotrimoxazole prophylaxis.

Assessing the effectiveness of antiretroviral regimens in cohort studies involving HIV-positive injection drug users

We compared the effectiveness of different highly active antiretroviral therapy (HAART) regimens considering, separately, history of injection drug use (IDU) (yes/no). DESIGN, METHODS: A total of 1163 HIV-infected patients initiated HAART between 1 January 2000 and 28 February 2009 in British Columbia, Canada, and were followed until 28 February 2010. HAART effectiveness was measured by the ability to achieve viral suppression below 50 copies/ml at 6 months. We compared HAART regimens containing efavirenz and boosted atazanavir. We developed logistic regression models using different techniques to control for potential confounders. Among the 1163 patients, 796 (68%) achieved viral suppression at 6 months (32% reporting a history of IDU). Different confounding models yielded very similar odds ratios for achieving viral suppression. Boosted atazanavir-based HAART demonstrated to be the most effective regimen, showing a surprisingly higher benefit for patients with a history of IDU (odds ratios from different models ranged from 1.74-1.95 to 1.45-1.51). The literature has conflicting results regarding the effectiveness of HAART to treat HIV infection among those with a history of IDU. We have shown that most patients, with and without a history of IDU, were able to achieve viral suppression at 6 months. Boosted atazanavir-based HAART was the most resilient regimen and it was more effective than efavirenz-based HAART among IDUs. Given the limited inclusion of IDU in clinical trials of HAART's efficacy, a randomized clinical trial comparing different first-line HAART regimens among IDU is warranted based on these results.

Cost-Effectiveness of Antiretroviral Therapy for Multidrug-Resistant HIV: Past, Present, and Future

In the early years of the highly active antiretroviral therapy (HAART) era, HIV with resistance to two or more agents in different antiretroviral classes posed a significant clinical challenge. Multidrug-resistant (MDR) HIV was an important cause of treatment failure, morbidity, and mortality. Treatment options at the time were limited; multiple drug regimens with or without enfuvirtide were used with some success but proved to be difficult to sustain for reasons of tolerability, toxicity, and cost. Starting in 2006, data began to emerge supporting the use of new drugs from the original antiretroviral classes (tipranavir, darunavir, and etravirine) and drugs from new classes (raltegravir and maraviroc) for the treatment of MDR HIV. Their availability has enabled patients with MDR HIV to achieve full and durable viral suppression with more compact and cost-effective regimens including at least two and often three fully active agents. The emergence of drug-resistant HIV is expected to continue to become less frequent in the future, driven by improvements in the convenience, tolerability, efficacy, and durability of first-line HAART regimens. To continue this trend, the optimal rollout of HAART in both rich and resource-limited settings will require careful planning and strategic use of antiretroviral drugs and monitoring technologies.

Effects of Highly Active Antiretroviral Therapy on Platelet Activating Factor Metabolism in Naïve HIV-Infected Patients: II) Study of the Abacavir/Lamivudine/Efavirenz Haart Regimen

Human Immunodeficiency Virus (HIV)-infected patients are at increased risk for cardiovascular diseases partly due to chronic inflammation. Some antiretroviral drugs and Highly Active Anti-Retroviral Therapy (HAART) regimens seem to be related and amplify this increased risk, especially the ones containing abacavir. Platelet-Activating-Factor (PAF) is a potent inflammatory mediator that is implicated in both cardiovascular diseases and HIV-related manifestations. Our objective is to study the in vivo effect of the abacavir/lamivudine/efavirenz first-line HAART regimen on PAF metabolism in HIV-infected patients. The specific activities of PAF basic biosynthetic enzymes in leukocytes and platelets, PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (Lyso-PAF-AT), but also those of PAF-basic catabolic enzymes, PAF acetylhydrolase (PAF-AH) in leukocytes and platelets and Lipoprotein-associated-Phospholipase-A2 (LpPLA2) in plasma, were measured in blood samples of 10 asymptomatic naïve male HIV-infected patients just before and after 1, 3 and 6 months of treatment. CD4 cell counts, viral load and several biochemical markers were also measured in the same blood samples of these patients. The repeated ANOVA measures and the Pearson r criterion were used for studying statistical differences and correlations - partial correlations respectively. Even though viral load was decreased and CD4 cell counts were beneficially increased after treatment with the abacavir/lamivudine/efavirenz regimen, the main enzyme of the remodelling PAF-synthesis that is implicated in pro-atherogenic inflammatory procedures, Lyso-PAF-AT activity, was increased at 3 months of treatment in both leukocytes and platelets, while the main enzyme of PAF-degradation, PAF-AH, was increased as a response only in leukocytes at the 3rd month. Although the abacavir/lamivudine/efavirenz HAART regimen exhibits very efficient antiretroviral activities, on the other hand it induces an in vivo transient increase in the inflammation-related remodeling PAF-biosynthetic pathway. This finding supports the hypothesis of inflammation-mediated increased cardiovascular risk in HIV-infected patients during the first months of abacavir-containing HAART.

Adverse Events in HIV- infected Children on Antiretroviral Therapy at a Teaching Hospital in Lagos, Nigeria: A Retrospective Study

Background: Highly active antiretroviral therapy (HAART) program requires adequate monitoring of the potential adverse events to the antiretroviral (ARV) drugs. We investigated the ARV drug combinations prescribed for HIV- infected children and their suspected adverse events. Methods: This is a retrospective and descriptive study involving HIV- infected children less than 15 years old who received treatment at the APIN clinic, Lagos University Teaching Hospital (LUTH) in Nigeria. The case files of 80 patients initiated on HAART, between January 2008 and December 2009, were reviewed. Their demographics, clinical details and medication use, the prescribed HAART regimen, and the suspected clinical and laboratory adverse events were extracted. Results: The patients were female (46; 57.5%) preponderant with a median age of 3 (IQR: 1.1-6.0) years. Zidovudine- lamivudine- nevirapine (AZT-3TC-NVP) combination (74; 92.5%) was the most frequently prescribed first-line regimen. Thirty three patients changed their first-line HAART to abacavir-lamivudine-lopinavir boosted with ritonavir (ABC-3TC-LVP/r) (11; 33.3%), and zidovudine- lamivudine- abacavir- lopinavir boosted with ritonavir (AZT-3TC-ABC-LVP/r) (8; 24.2%) combinations. Of the 80 patients included in the study, 38(47.7%) experienced 142 adverse events. The most frequently experienced clinical adverse events were nevirapine-induced skin rashes (93; 65.5%), vomiting (19; 13.4%), and pallor (12; 8.5%). Macrocytosis (22/72; 30.6%), anaemia (6/72; 8.3%), and thrombocytopenia (2/72; 2.8%) were the commonest haematological adverse events associated with zidovudine. Conclusions: The HAART regimens used for HIV-infected children in this study have a good safety profile. Their few adverse events suggest a need for prospective pharmacovigilance to effectively monitor the toxicities of ARV drugs.

HIV and hepatitis C co-infection

Highly active antiretroviral therapy (HAART)-related hepatotoxicity, a relevant side effect in HIV/hepatitis C virus (HCV) co-infected patients, has evolved over time. Antiretroviral therapy might have a positive effect on the liver of HIV/HCV co-infected patients, but data are conflicting. HIV treatments have evolved and we have currently a drug armamentarium with a good liver safety profile. Most of the current first-line HAART regimens recommended by guidelines fit well to HIV/HCV co-infected patients. There are now multiple retrospective studies that suggest a possible benefit of HIV control and protection of CD4 cell counts to the liver of HIV/HCV co-infected patients. However, data are conflicting at times. This factor along with the methodological limitations of these studies prevent us from drawing definitive conclusions. Even assuming a positive effect, HAART does not appear to fully correct the adverse effect of HIV infection on HCV-related outcomes. In the era of HCV direct antiviral agents, the timing of HIV and HCV therapies has to be individualized in HIV/HCV co-infected patients given the variety of scenarios. With current HIV drug armamentarium it is possible to construct HAART regimens with optimal liver safety profile for HCV co-infected patients. The possible positive effect of HAART on the HCV-infected liver should not distract from the main intervention, which is HCV eradication with specific treatment.