References

Pallela FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatients Study Investigators. N Engl J Med 1998 338 853-860. 2. Shevitz A, Wanke CA, Falutz J, Kotler DP. Clinical perspectives on HIV-associ-ated lipodystrophy syndrome an update. AIDS 2001 15 1917-1930. 3. Carr A, Samaras K, Burton S, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients...

Mitochondrial Toxicity In Children

Hyperlactatemia does occur in the pediatric population (reviewed in ref. 104). There are several concerning reports regarding HIV-exposed but uninfected infants who developed hyperlactatemia from in utero exposure to HAART. One prospective study examined serial lactate levels in 25 infants born to HAART-treated mothers and reported that 92 of infants had elevated lactate levels, with 35 of the cohort demonstrating levels greater than 5 mmol L (105). Only one infant was symptomatic. All of the...

Basic Understanding Of Mitochondria

The most important and critical mitochondrial function is oxidative phos-phorylation, a mechanism by which the energy derived from metabolism of nutrients in the presence of oxygen is transformed into adenosine triphosphate (ATP). Figure 1 describes the mitochondrial oxidative energy metabolism. The system of oxidative phosphorylation includes five multienzyme complexes, designated as electron-transport chain complexes I through V. These enzymes are encoded by either mitochondrial or nuclear...

What Laboratory Studies Are Needed For Initiation In Monitoring Of Therapy In Developing Countries

Laboratory tests in Western countries costing between 1000 and 2000 annually are used to provide serial CD4 counts, viral loads, occasional resistance tests, and other laboratory tests for initiating and monitoring HIV care. In many countries in Africa, few laboratory studies are available and most patients have no resources to pay for laboratory studies. As a result, the majority of patients are treated without Western-type laboratory support. Several initiatives need to urgently be taken....

Management Of Neuropathy Associated With Nucleoside Reverse Transcriptase Inhibitor Therapy

Complaints of pain or paresthesias in the lower extremities of a patient taking ddI, ddC, or d4T suggests the possibility of a toxic neuropathy and warrants detailed evaluation. Compared with HIV-associated DSP, toxic neuropathies appear more abruptly and progress more quickly, thus, an individual who develops such progressive symptoms within several months after the introduction of a potentially neurotoxic antinucleoside agent is more likely to have a toxic neuropathy. The diagnosis, however,...

The Role Of Delavirdine In Clinical Practice Table

According to its package insert, delavirdine is indicated for the treatment of HIV infection in combination with at least two other agents when antiretroviral therapy is warranted from a clinical perspective. Of seven women who became pregnant while receiving delavirdine as part of a clinical trial, three had ectopic pregnancies, one delivered an infant with a small muscular ventricular septal defect, and three had normal deliveries. In light of this (along with limited animal data suggesting...

Index

Abacavir, 33-35, 56-67, 100, 101, 188192, 203-205, 214, 217, 218, 222-227, 442 arm, 63-65, 139 hypersensitivity, 59, 62-64, 66 monotherapy, 59, 64, 190, 191, 193 pharmacokinetics, 58 resistance, 65 toxicity, 66 ABC See Abacavir Academic Alliance, 511 Acetyl CoA, 282 Acetyl-L-carnitine, 254, 255, 260, 271 ACTG, 37, 41, 49, 63, 64, 84, 110, 111, 113, 304, 305, 363, 364, 382, 383, 390, 391. See also AIDS Clinical Trials Group Activation, 3, 22, 94, 157, 159, 209, 210, 212, 215-217, 219-222, 224,...

Can Care Be Scaled Up Without Altering The Priority Of Prevention

In all societies, prevention initiatives, including strengthening of public health systems, is continually at odds with monies allocated to care. In most Western societies, a hugely disproportionate amount of resources is provided for care services that do little more for many patients than delay death by weeks to months. Meanwhile, public health activities are severely underfunded by most governments. In several countries, notably Thailand and Uganda, prevention has been remarkably successful...

Factors That May Influence Intracellular Phosphorylation

Because the NRTIs require intracellular activation for antiretroviral activity, influences on the enzymes responsible for activation can modulate drug activity. In vitro, cellular factors have been shown to alter antiretroviral activity. The activation state of the cell may change the relationship between drug triphos-phate and endogenous triphosphate. For instance, in activated cells, the ratios of ZDVTP to deoxythymidine triphosphate (dTTP) and of d4T triphosphate to dTTP are greater than in...

Didanosine

Didanosine (also known as ddI) is available in its original buffered formulations (Videx) and as a delayed-release formulation with enteric-coated beadlets Selected Laboratory and Hematological Abnormalities From Combination Studies of Stavudine (Pooled Data) (6)a Parameter n 467 ( of patients)c Total bilirubin (> 2.6 x ULN) 0 Neutropenia (ANC < 750 mm3) 5 Anemia (hemoglobin < 8 g dL) < 1 Thrombocytopenia (platelets < 50,000 cells mm3) 2 AST, aspartate aminotransferase ALT, alanine...

Info

NVP, nevirapine od, once daily bd, twice daily EFV, efavirenz lab, laboratory value Treatment failure defined as a less than 1 log10 copies mL decline in HIV RNA pVL in first 12 wk, two consecutive pVL levels greater than 50 copies mL from week 24 onwards, a new AIDS-defining illness or death, or a change of allocated treatment Percentage of patients with at least one grade 3 or 4 adverse events (AE) cGrade 3 or 4 elevations in AST, ALT, or total bilirubin levels Excluding isolated (-glutamic...

Nd

Vd, volume of distribution CSF, cerebrospinal fluid ND, not determined Pediatric patients (8-mo to 19-yr old) demonstrate a lower oral bioavailability (25 ), smaller Vd (28 L m2), and shorter half-life (0.8 h) (60,65) Vd, volume of distribution CSF, cerebrospinal fluid ND, not determined Pediatric patients (8-mo to 19-yr old) demonstrate a lower oral bioavailability (25 ), smaller Vd (28 L m2), and shorter half-life (0.8 h) (60,65) Buffered didanosine, the first available formulation of...

Clinical Manifestations Of Mitochondrial Toxicity

Symptomatic Forms of Hyperlactatemia Lactic acidosis is the most dramatic manifestation of NRTI-associated mitochondrial dysfunction. Lactic acidosis has been reported in HIV-infected patients since the early 1990s, but recent clusters of reports increased physicians' awareness about this potentially fatal syndrome. Fortunately, severe lactic acidosis remains a rare occurrence. The typical clinical presentation is one of precipitous occurrence of nausea, vomiting, abdominal pain, severe...

Therapeutic Interventions In The Prevention Of Vertical Hiv Transmission

The initial reports of HIV in children highlighted the fact that this emerging infection could be transmitted from an asymptomatic mother to her newborn child (51), that HIV-infected infants had faster disease progression, and that pediatric AIDS had a high mortality rate (52,53). The poor prognosis of pediatric AIDS led investigators to design strategies to reduce perinatal HIV-1 transmission. ZDV, the only Food and Drug Administration-approved antiretroviral drug in the mid-1980s, was the...

Hiv Rt Crystal Structures

The Architecture of the HIV-1 RT Heterodimer A number of crystal structures of HIV-1 RT have been published during the last 10 years mainly of the full RT heterodimer. In addition, structures of some RT domains have been determined, including the C-terminal HIV-1 RNase H (25) and N-terminal fragments from HIV-1 (26) and murine Moloney RTs (27). The HIV-1 RT heterodimer structures determined, to date, can be divided into three general categories 1. complexes containing nucleic acid, which...