Highly Active Antiretroviral Therapy Regimen Research Articles

HIV Infection, Antiretroviral Therapy and Cardiovascular Risk.

In the last 15 years, highly active antiretroviral therapy (HAART) has determined a dramatic reduction of both morbidity and mortality in human immunodeficiency virus (HIV)-infected subjects, transforming this infection in a chronic and manageable disease. Patients surviving with HIV in the developed world, in larger number men, are becoming aged. As it would be expected for a population of comparable age, many HIV-infected individuals report a family history of cardiovascular disease, a small proportion have already experienced a cardiovascular event and an increasing proportion has diabetes mellitus. Smoking rate is very high while an increasing proportion of HIV-infected individuals have dyslipidaemia. Studies suggest that these traditional risk factors could play an important role in the development of cardiovascular disease in these patients as they do in the general population. Thus, whilst the predicted 10-year cardiovascular disease risk remains relatively low at present, it will likely increase in relation to the progressive aging of this patient population. Thus, the long-term follow-up of HIV infected patients has to include co-morbidity management such as cardiovascular disease prevention and treatment. Two intriguing aspects related to the cardiovascular risk in patients with HIV infection are the matter of current investigation: 1) while these subjects share many cardiovascular risk factors with the general population, HIV infection itself increases cardiovascular risk; 2) some HAART regimens too influence atherosclerotic profile, partly due to lipid changes. Although the mechanisms involved in the development of cardiovascular complications in HIV-infected patients remain to be fully elucidated, treatment guidelines recommending interventions to prevent cardiovascular disease in these individuals are already available; however, their application is still limited.

Maternal or Infant Antiretroviral Drugs to Reduce HIV-1 Transmission

There is a critical need for effective highly active antiretroviral therapy (HAART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in low-resource areas of the world where replacement feeding is not feasible. The most effective HAART regimen to prevent HIV transmission during breast-feeding is unknown. This study compared different HAART regimens to determine whether they differ with respect to virologic suppression during pregnancy and breast-feeding, pregnancy outcomes, and adverse effects in mothers and infants. The participants—560 pregnant HIV-1 infected women with CD4+ cell counts of ≥200—were randomly assigned to receive either a coformulation of abacavir, zidovudine, and lamivudine (the nucleoside reverse-transcriptase inhibitor [NRTI] group) or a coformulation of lopinavir-ritonavir plus zidovudine-lamivudine (the protease inhibitor group). Both the regimens were administered between 26 and 34 weeks' gestation and were continued through planned weaning by 6 months postpartum. The observational group—170 women with CD4+ cell counts <200 cells—received standard-of-care treatment (nevirapine plus zidovudine-lamivudine). Infants were given single-dose nevirapine at birth and zidovudine from birth through 4 weeks. There was no significant difference between any of the 3 regimens in the rate of virologic suppression (decrease in plasma HIV-1 RNA level) to less than 400 copies per mL both at delivery (96% in the NRTI group, 93% in the protease inhibitor group, and 94% in the observational group) and throughout the breast-feeding period (92% in the NRTI group, 93% in the protease inhibitor group, and 95% in the observational group). At 6 months, the rates of mother-to-child transmission were low; only 1.1% (8/709) of live-born infants were infected (95% confidence interval, 0.5–2.2). Of the 8 infants infected at 6 months, 6 were infected in utero (4 in the NRTI group, 1 in the protease inhibitor group, and 1 in the observational group) and 2 infants were infected through late breast-feeding transmission (both in the NRTI group). Adverse events required modification of the HAART regimen in 2% of both intervention groups and 11% in the observational group. These findings show that all HAART regimens are highly effective for virologic suppression at delivery and throughout breast-feeding, with an overall rate of mother-to-child HIV transmission of 1.1% at 6 months.

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.

Safety and Efficacy of Fosamprenavir in Human Immunodeficiency Virus-infected Pregnant Women

To the Editors: In the United States, highly active antiretroviral therapy (HAART) is recommended during pregnancy to reduce the risk of perinatal transmission of human immunodeficiency virus (HIV) and to improve the health of the mother.1 Many HAART regimens used during pregnancy include a protease inhibitor.1 Although the protease inhibitor fosamprenavir has been available since 2003, no prospective data to date have been presented regarding its safety and efficacy when used during pregnancy. COL108577 was a retrospective, observational case series evaluating mother and infant outcomes for all HIV-positive pregnant women, from one clinical practice, who delivered while taking fosamprenavir. Patients' charts dating from October 2003 to date were reviewed. Given the expected sample size of approximately 10 mother-infant pairs, no statistical testing was planned, and results of abstracted data were intended to be descriptive. Baseline was defined as the last observation before fosamprenavir initiation, whereas the delivery value was the observation at or closest to delivery. Data were available for 9 mother-infant pairs. Median baseline age of the mothers was 33 years (range, 20–43). Six women were naive to HAART at baseline. In addition to fosamprenavir, HAART regimens included boosting with ritonavir (n = 7) and initial nucleoside reverse transcription inhibitor backbones of zidovudine/lamivudine (n = 6), tenofovir/emtricitabine (n = 1), didanosine/emtricitabine (n = 1), and abacavir/lamivudine (n = 1). During the observation period, 1 woman switched her zidovudine/lamivudine backbone to tenofovir/emtricitabine. Improvements were observed both in viral load and in CD4+ T-cell count consistently across the study cohort (Table 1). Compared with baseline, delivery viral loads decreased for each of the 8 women who had started with a detectable level; and for the 1 woman with an undetectable viral load (<50 copies/mL) at baseline, her viral load remained undetectable at delivery. Additionally, CD4+ T-cell counts increased for all 9 women. No hepatic, renal, or pancreatic abnormalities were seen in the mothers. The regimens were well-tolerated. Delivery modes were as follows: 4 vaginal, 4 scheduled c-section, and 1 emergent c-section. Median gestational age was 37 6/7 weeks (range, 35 4/7–42).TABLE 1: Maternal Characteristics and Outcomes (n = 9)For infants outcomes, the median of the 3 APGAR score readings was 8.67 (range, 7.33–9.00). Median birth weight and height were 3041 g (range, 2175–4216) and 51 cm (range, 43.8–58.4), respectively. CNS abnormalities, sometimes of concern with sulfonamide-containing products, were not observed in the infants, nor were any adverse events attributed to fosamprenavir. To date, all infants (n = 9) have tested negative for HIV by polymerase chain reaction. In conclusion, this small study showed that fosamprenavir-based HAART was well-tolerated in a cohort of pregnant women, with most of the women achieving favorable immunologic and virologic responses comparable to those reported with other protease inhibitor-based regimens administered during pregnancy.2–5 In infants, good birth outcomes and no significant adverse events were reported, and no mother-to-child transmission of HIV was detected. Claudia Martorell, MD, MPH, FACP The Research Institute [email protected] Eileen Theroux, RN, BSN Department of Pediatrics Baystate Medical Center Arlene Bermudez, AS The Research Institute Springfield, MA Jane Garb, MS Health Geographics Program Baystate Medical Center Springfield, MA Debra Kronschnabel, PharmD ViiV Healthcare Research Triangle Park, NC Katrina Oie, PhD GlaxoSmithKline Research Triangle Park, NC

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.

The use of cell-delivered gene therapy for the treatment of HIV/AIDS

HIV/AIDS is a disease that impairs immune function, primarily by decreasing T-lymphocyte count. Its progression can be contained by highly active antiretroviral therapy (HAART), but there are side effects that can be severe, and the development of resistance often forces the physician to modify the HAART regimen. There are no vaccines available for HIV. An alternative approach that could provide a path to a curative therapy is the use of cell-delivered gene therapy in which an anti-HIV gene(s) is introduced into hematopoietic cells to produce a population that is protected from the effects of HIV. In this paper, we review the field and discuss an approach using a short hairpin RNA to CCR5, an important co-receptor for HIV.

How Long Is the Right Interval for Assessing Antiretroviral Pharmacy Refill Adherence?

How Long Is the Right Interval for Assessing Antiretroviral Pharmacy Refill Adherence?

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.

Measures of site resourcing predict virologic suppression, immunologic response and HIV disease progression following highly active antiretroviral therapy (HAART) in the TREAT Asia HIV Observational Database (TAHOD).

Surrogate markers of HIV disease progression are HIV RNA in plasma viral load (VL) and CD4 cell count (immune function). Despite improved international access to antiretrovirals, surrogate marker diagnostics are not routinely available in resource-limited settings. Therefore, the objective was to assess effects of economic and diagnostic resourcing on patient treatment outcomes. Analyses were based on 2333 patients initiating highly active antiretroviral therapy (HAART) from 2000 onwards. Sites were categorized by World Bank country income criteria (high/low) and annual frequency of VL (> or = 3, 1-2 or <1) or CD4 (> or = 3 or <3) testing. Endpoints were time to AIDS/death and change in CD4 cell count and VL suppression (<400 HIV-1 RNA copies/mL) at 12 months. Demographics, Centers for Disease Control and Prevention (CDC) classification, baseline VL/CD4 cell counts, hepatitis B/C coinfections and HAART regimen were covariates. Time to AIDS/death was analysed by proportional hazards models. CD4 and VL endpoints were analysed using linear and logistic regression, respectively. Increased disease progression was associated with site-reported VL testing less than once per year [hazard ratio (HR)=1.4; P=0.032], severely symptomatic HIV infection (HR=1.4; P=0.003) and hepatitis C virus coinfection (HR=1.8; P=0.011). A total of 1120 patients (48.2%) had change in CD4 cell count data. Smaller increases were associated with older age (P<0.001) and 'Other' HIV source exposures, including injecting drug use and blood products (P=0.043). A total of 785 patients (33.7%) contributed to the VL suppression analyses. Patients from sites with VL testing less than once per year [odds ratio (OR)=0.30; P<0.001] and reporting 'Other' HIV exposures experienced reduced suppression (OR=0.28; P<0.001). Low measures of site resourcing were associated with less favourable patient outcomes, including a 35% increase in disease progression in patients from sites with VL testing less than once per year.

Viral Decay Kinetics in the Highly Active Antiretroviral Therapy-Treated Rhesus Macaque Model of AIDS

To prevent progression to AIDS, persons infected with human immunodeficiency virus type 1 (HIV-1) must remain on highly active antiretroviral therapy (HAART) indefinitely since this modality does not eradicate the virus. The mechanisms involved in viral persistence during HAART are poorly understood, but an animal model of HAART could help elucidate these mechanisms and enable studies of HIV-1 eradication strategies. Due to the specificity of non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for HIV-1, we have used RT-SHIV, a chimeric virus of simian immunodeficiency virus with RT from HIV-1. This virus is susceptible to NNRTIs and causes an AIDS-like disease in rhesus macaques. In this study, two groups of HAART-treated, RT-SHIV-infected macaques were analyzed to determine viral decay kinetics. In the first group, viral loads were monitored with a standard TaqMan RT-PCR assay with a limit of detection of 50 viral RNA copies per mL. Upon initiation of HAART, viremia decayed in a bi-phasic manner with half-lives of 1.7 and 8.5 days, respectively. A third phase was observed with little further decay. In the second group, the macaques were followed longitudinally with a more sensitive assay utilizing ultracentrifugation to concentrate virus from plasma. Bi-phasic decay of viral RNA was also observed in these animals with half-lives of 1.8 and 5.8 days. Viral loads in these animals during a third phase ranged from 2–58 RNA copies/mL, with little decay over time. The viral decay kinetics observed in these macaques are similar to those reported for HIV-1 infected humans. These results demonstrate that low-level viremia persists in RT-SHIV-infected macaques despite a HAART regimen commonly used in humans.

Impact of maternal HAART on the prevention of mother-to-child transmission of HIV: results of an 18-month follow-up study in Ouagadougou, Burkina Faso

Mother-to-child transmission remains the main cause of global pediatric HIV infections, especially in sub-Saharan Africa. Many interventions based on single-dose antiretroviral therapy have been implemented to reduce the mother-to-child transmission of HIV. In resource-limited settings, highly active antiretroviral therapy (HAART) has only been recommended for HIV-infected pregnant women requiring treatment for their own health. Here, we assessed the efficacy over 18 months of maternal HAART versus peripartum short-course antiretroviral therapy (SCART) regimens for the prevention of mother-to-child transmission (PMTCT) of HIV. We conducted a retrospective cohort study of patients from two medical centers in Ouagadougou, Burkina Faso. The PMTCT files and registers from 1 January 2003 to 31 December 2006 were obtained from routine data collected at these sites. The main assessment criterion was the rate of HIV-1 positivity in children born to HIV-positive mothers as measured with HIV-1 rapid tests at 18 months. A total of 586 pregnant HIV-1-infected women in PMTCT programs were selected. Among these women, 260 were undergoing HAART and 326 received single-dose nevirapine (91.3%) or single-dose zidovudine (8.7%) at delivery. HIV-1 serological tests were performed on 454 children at 18 months old. The rate of HIV-1 vertical transmission was 0% (0/195) in the HAART group and 4.6% (12/259) in the single-dose monotherapy group (P<0.01). Eight infants in the HAART cohort and 30 in the SCART cohort were breastfed; three in the SCART group were HIV-positive. A total of 62 children died, 19 in the HAART group and 43 in the single-dose monotherapy group. Our study confirms that HAART for mothers effectively reduces the risk of infant HIV infection while preserving the breastfeeding option for mothers.

Successful Immunologic and Virologic Outcomes in Elderly HIV-Infected Patients

Successful Immunologic and Virologic Outcomes in Elderly HIV-Infected Patients

Poor health-related quality of life and abnormal psychosocial adjustment in Italian children with perinatal HIV infection receiving highly active antiretroviral treatment

To evaluate health-related quality of life (HRQL), social competence, and behavioral problems in children with perinatal HIV infection receiving highly active antiretroviral therapy (HAART), a cross-sectional study was performed at the Department of Pediatrics, University of Brescia. We evaluated HRQL, social competence, and behavioral problems in 27 HIV-infected children compared with age and sex-matched control subjects using the Pediatric Quality of Life Inventory (PedsQL) and the Child Behavior Checklist (CBCL), respectively. On the PedsQL 4.0 Generic Core Scale, HIV-infected subjects displayed significantly reduced physical (p=0.043) and psychosocial health (p=0.021) functioning, particularly at school (p=0.000), compared with healthy subjects, resulting in a significantly reduced total score (p=0.013). Assessment of social competence and the behavioral features of HIV-infected children by means of the CBCL revealed severe limitations of functioning in HIV-infected children who had impaired social ability. Children with HIV-RNA above the threshold level of 50 had higher scores on the CBCL delinquent behavior (p=0.021) and school competence (p=0.025) subsets. Although the introduction of HAART regimens has prolonged the survival of HIV-infected children, other factors, including disease morbidity and familial and environmental conditions, negatively affect their quality of life, thereby contributing to increased risk for behavioral problems.

Evaluation of the effectiveness and safety of chemoprophylaxis for vertical HIV transmission, by using the regimens of monotherapy and highly active antiretroviral therapy

The study including 69 pregnant women diagnosed as having HIV infection who received chemoprophylaxis for vertical HIV infection evaluated the effectiveness and safety of the regimens of monotherapy and highly active antiretroviral therapy (HAART) used during pregnancy. There was a significant reduction in the levels of HIV RNA and an increase in the CD4 lymphocyte count in the patients receiving both chemoprophylaxis regimens. The efficiency of HAART regimens to prevent vertical HIV transmission was significantly higher than that of monoprophylaxis. The use of antiretroviral drugs was safe as monotherapy and in the HAART regimens during pregnancy.

Increased Levels of Platelet Microparticles in HIV-Infected Patients With Good Response to Highly Active Antiretroviral Therapy

Increased Levels of Platelet Microparticles in HIV-Infected Patients With Good Response to Highly Active Antiretroviral Therapy

Management and outcome of HIV in pregnancy

IntroductionAt the end of 2008, 1 in 486 pregnant women in the UK were infected with HIV. Prior to widespread use of Highly Active Anti-Retroviral Therapy (HAART), Caesarean section was...

Effects of highly active antiretroviral therapy duration and regimen on risk for mother-to-child transmission of HIV in Johannesburg, South Africa.

Limited information exists about effects of different highly active antiretroviral therapy (HAART) regimens and duration of regimens on mother-to-child transmission (MTCT) of HIV among women in Africa who start treatment for advanced immunosuppression. Between January 2004 to August 2008, 1142 women were followed at antenatal antiretroviral clinics in Johannesburg. Predictors of MTCT (positive infant HIV DNA polymerase chain reaction at 4-6 weeks) were assessed with multivariate logistic regression. Mean age was 30.2 years (SD = 5.0) and median baseline CD4 count was 161 cells per cubic millimeter (SD = 84.3). HAART duration at time of delivery was a mean 10.7 weeks (SD = 7.4) for the 85% of women who initiated treatment during pregnancy and 93.4 weeks (SD = 37.7) for those who became pregnant on HAART. Overall MTCT rate was 4.9% (43 of 874), with no differences detected between HAART regimens. MTCT rates were lower in women who became pregnant on HAART than those initiating HAART during pregnancy (0.7% versus 5.7%; P = 0.01). In the latter group, each additional week of treatment reduced odds of transmission by 8% (95% confidence interval: 0.87 to 0.99, P = 0.02). Late initiation of HAART is associated with increased risk of MTCT. Strategies are needed to facilitate earlier identification of HIV-infected women.

Effects of long‐term use of HAART on oral health status of HIV‐infected subjects

The aim of this study was to determine the effects of long-term use of highly active antiretroviral therapy (HAART) on oral health status of HIV-infected subjects. Oral examination and measurement of saliva flow rate of both unstimulated and wax-stimulated whole saliva were performed in HIV-infected subjects with and without HAART, and in non-HIV individuals. The following data were recorded; duration and risk of HIV infection, type and duration of HAART, CD4 cell count, viral load, presence of orofacial pain, oral dryness, oral burning sensation, oral lesions, cervical caries, and periodontal pocket. Multiple logistic regression analysis was performed to determine the effects of long-term use of HAART on oral health status of HIV-infected subjects. One hundred and fifty-seven HIV-infected subjects - 99 on HAART (age range 23-57 years, mean 39 years) and 58 not on HAART (age range 20-59 years, mean 34 years) - and 50 non-HIV controls (age range 19-59 years, mean 36 years) were enrolled. The most common HAART regimen was 2 NRTI + 2 NNRTI. HIV-infected subjects without HAART showed greater risks of having orofacial pain, oral dryness, oral lesions, and periodontal pockets than those with short-term HAART (P < 0.01). The subjects with long-term HAART were found to have a greater risk of having oral lesions than those with short-term HAART (P < 0.05). The unstimulated and stimulated salivary flow rates of the subjects with HAART were significantly lower than in those without HAART (P < 0.05). We conclude that long-term HAART has adverse effects on oral health status of HIV-infected subjects.

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.

Enhanced HIV Testing, Treatment, and Support for HIV-Infected Substance Users

Enhanced HIV Testing, Treatment, and Support for HIV-Infected Substance Users