News HIV/AIDS News & Information - Part 183

03 Apr

Herpes simplex virus

TEM micrograph of a herpes simplex virus.

Chronic persistent infection with herpes simplex virus (HSV) is common in patients with advanced HIV disease and is a Centers for Disease Control (CDC)-defined index infection in establishing an AIDS diagnosis.

Lesions may appear as grouped blisters that rupture, crust, and heal in 7 to 10 days. Once severely immunosuppressed, HIV-infected persons often experience chronic lesions that continue to expand and form large, painful ulcers and crusted erosions, 2 to 10 cm or larger.

Periungual infection is another characteristic manifestation of HSV-2 infection in the HIV-infected patient; all paronychial lesions should be cultured for HSV.

Fluorescent antibody testing or viral culture of fresh lesions are diagnostic.

Treatment

Acyclovir (200 to 400 mg orally 5 times daily) should be prescribed until the ulcers heal, which may take several weeks. Chronic suppressive therapy may be instituted with acyclovir (400 mg orally twice daily) to reduce recurrences. Famciclovir ( Famvir, 250 mg 3 times daily) and valacyclovir ( Valtrex, 100 mg twice daily) have higher bioavailability and require less frequent dosing.

Acyclovir-Resistant HSV Infection. Large chronic perianal, perioral, or periungual ulcers that fail to heal with acyclovir are often caused by acyclovir-resistant HSV-2. Treatment with foscarnet and continuous-infusion acyclovir is beneficial. Trifluridine ophthalmic solution may be effective for lesions that do not respond to acyclovir and foscarnet.

Images:

Click on any of the Herpes images below to enlarge.

Herpes Simplex Virus Herpes Simplex Virus (HSV)HSV

 

02 Apr

Bacillary angiomatosis

Bacillary AngiomatosisBacillary angiomatosis

Bacillary angiomatosis is an infection caused by two species of Bartonella – B. henselae and B. quintana. These bacteria are extremely difficult to culture. One of the agents causing bacillary angiomatosis, B. henselae, is associated with cat scratch disease. Cat exposure and cat scratches are risk factors for acquiring bacillary angiomatosis.

Visceral disease may include osseous lesions, hepatic and splenic involvement, lymph node disease, pulmonary lesions, brain lesions, and widespread fatal systemic involvement.

Clinical Features

Bacillary angiomatosis is characterized by pyogenic granulomas — fleshy, friable, protuberant papules-to-nodules that tend to bleed very easily. In addition, deep cellulitic plaques and subcutaneous nodules may occur. Lesions number from a few to hundreds. Diagnosis is confirmed by biopsy.

Fever, night sweats, and anemia are common. Involvement of the liver and spleen is the most commonly diagnosed form of visceral disease. These patients present with abdominal pain, fevers, elevated levels on liver function tests, and hepatosplenomegaly.

Treatment.  (500 mg orally 4 times daily) or (100 mg orally twice daily) is effective. Therapy should continue for 8 weeks. Patients with visceral disease should receive 4 months of therapy.

01 Apr

Dermatologic Manifestations of HIV Infection – part 1

Infectious cutaneous conditions

Staphylococcus aureus infections

Staphylococcus aureus is the most common bacterial skin infection in persons with HIV disease.

Bullous impetigo. Bullous impetigo is most common in hot, humid weather, presenting as very superficial blisters or erosions, most commonly seen in the groin or axilla.

Ecthyma is an eroded or superficially ulcerated lesion with an adherent crust. Purulent material is present under this crust.

FolliculitisFolliculitis

Folliculitis due to S. aureus occurs most commonly in the hairy areas of the trunk, groin, axilla, or face. Gram’s stain and culture of pustules confirms the diagnosis.

Often the follicular lesions of the trunk are intensely pruritic and may be mistaken for scabies. About 50% of HIV-infected persons with scabies have coexistent S. aureus folliculitis.

Treatment of cutaneous staphylococcal lesions

Very superficial lesions, like bullous impetigo, often respond to an antistaphylococcal antibiotic, such as dicloxacillin (500 mg given PO qid) or 7-10 days. Combinations, especially a dicloxacillin or cephalexin plus rifampin (600 mg once daily), are often necessary.

Washing the infected area once daily or every other day with an antibacterial agent (Hibiclens, Betadine) helps remove crusts, dries lesions, and decreases surface bacterial concentration. Topical (1% or 2% solutions) applied twice daily may be used.

Loculated abscesses must be incised and drained when fluctuant. Intravenous antibiotics are required when significant cellulitis of or symptoms of bacteremia are present, appropriate. Intranasal mupirocin may reduce carriage rate and prevent relapses. Chronic oral may be required to prevent relapse.

26 Mar

Antiretroviral Therapy – Changing Therapy – part4

Criteria for Changing Therapy

  • Less than a 0.5–0.75 log reduction in plasma HIV RNA by 4 weeks following initiation of therapy, or less than a 1 log reduction by 8 weeks;
  • Failure to suppress plasma HIV RNA to undetectable levels within 4–6 months of initiating therapy.
  • Repeated detection of virus in plasma after initial suppression to undetectable levels, suggesting the development of resistance.
  • Any reproducible significant increase, defined as 3-fold or greater, from the nadir of plasma HIV RNA not attributable to intercurrent infection, vaccination, or test methodology except as noted above;
  • Persistently declining CD4 + T cell numbers, as measured on at least two separate occasions;
  • Clinical deterioration (Dlll). In this regard, a new AIDS-defining diagnosis that was acquired after the time treatment was initiated suggests clinical deterioration but may or may not suggest failure of antiretroviral therapy.

Therapeutic Options When Changing Antiretroviral Therapy

Table XIV summarizes some of the most important guidelines to follow when changing a patient’s antiretroviral therapy. Table XV outlines some of the treatment options available when a decision has been made to change the antiretroviral regimen. A change in regimen because of treatment failure should ideally involve complete replacement of the regimen with to which the patient is naïve and to which cross-resistance is not anticipated. This typically would include the use of 2 new NRTIs and one new PI or NNRTI, two PIs with one or two new NRTIs, or a PI combined with an NNRTI. Dose modifications may be required to account for  interactions when using combinations of PIs or a PI and NNRTI (Table XII).

Table 15. Possible Regimens For Patients Who Have Failed Antiretroviral Therapy

 

Prior Regimen New Regimen (Not listed in priority order)
2 NRTIs + 2 new NRTIs +

Nelfinavir (NFV)

RTV; or IDV; or SQV + RTV; or NNRTI## +
RTV; or NNRTI + IDV**

Ritonavir (RTV)

SQV + RTV**; NFV + NNRTI; or NFV + SQV

Indinavir (IDV)

SQV + RTV; NFV + NNRTI; or NFV + SQV

Saquinavir (SQV)

RTV + SQV; or NNRTI + IDV
2 NRTIs + NNRTI 2 new NRTIs + a protease inhibitor
2 NRTIs 2 new NRTIs + a protease inhibitor
2 new NRTIs + RTV + SQV
1 new NRTI
+ 1 NNRTI + a protease inhibitor
2 protease inhibitors + NNRTI
1 NRTI 2 new NRTIs + a protease inhibitor
2 new NRTIs + NNRTI
1 new NRTI + 1
NNRTI + a protease inhibitor

 

* These alternative regimens have not been proven to be clinically effective and were arrived at through discussion by the panel of theoretically possible alternative treatments and the elimination of those alternatives with evidence of being ineffective. Clinical trials in this area are urgently needed.

# RTV=ritonavir, IDV=indinavir, SQV=saquinavir, NVP=nevirapine, NFV=nelfinavir, DLV=delavirdine

** There are some clinical trials with viral burden data to support this recommendation

## Nevirapine induces and delavirdine inhibits CYP450 enzymes, and this must be considered in combining these with other agents. Efavirenz is a mixed inducer/inhibitor of CYP450 enzymes; concentration of concomitantly administered can be increased or decreased depending upon the specific enzyme pathway involved.

Treatment Regimen for Primary HIV Infection

The therapeutic regimen for acute HIV infection should include a combination of two nucleoside reverse transcriptase inhibitors and one potent protease inhibitor. Although most experience to date with protease inhibitors in the setting of acute HIV infection has been with ritonavir, indinavir or nelfinavir. Potential combinations of agents available are much the same as those used in established infection, listed in Table VI.

Duration of Therapy for Primary HIV Infection

Once therapy is initiated many experts would continue to treat the patient with agents indefinitely because viremia has been documented to reappear or increase after discontinuation of therapy (CII). The optimal duration and composition of therapy are unknown and ongoing clinical trials are expected to provide data relevant to these issues. The difficulties inherent in determining the optimal duration and composition of therapy initiated for acute infection should be considered when first counseling the patient regarding therapy. Buy antiviral drugs.

24 Mar

Antiretroviral Therapy – inhibitors – part3

Table 7. Characteristics of nucleoside reverse transcriptase inhibitors (NRTIs)

Initiating Therapy in Advanced HIV Disease

All patients diagnosed with advanced HIV disease, which is defined as any AIDS-defining condition should be treated with antiretroviral agents regardless of plasma viral levels. All patients with symptomatic HIV infection without AIDS, defined as the presence of thrush or unexplained fever, should also be treated.

Special Considerations in the Patient with Advanced Stage Disease

Some patients present with opportunistic infections, wasting, dementia or malignancy and are first diagnosed with HIV infection at this advanced stage of disease. All patients with advanced HIV disease should be treated with antiretroviral therapy. When the patient is acutely ill with an OI or other complication of HIV infection, the clinician should consider clinical issues such as drug toxicity, ability to adhere to treatment regimens, and laboratory abnormalities when determining the timing of initiation of antiretroviral therapy. Once therapy is initiated, a maximally suppressive regimen, such as 2 NRTIs and a protease inhibitor, should be used, as indicated in Table VI. Advanced stage patients being maintained on an antiretroviral regimen should not have the therapy discontinued during an acute opportunistic infection or malignancy, unless there are concerns regarding drug toxicity, intolerance, or drug interactions.

Class Adverse Events

Several class-related adverse events have been recognized with antiretroviral during the post-marketing period. For nucleoside analogue reverse transcriptase inhibitors (NRTIs), lactic acidosis with hepatomegaly and hepatic steatosis has been reported. For protease inhibitors reports of hyperglycemia/diabetes mellitus, increased bleeding episodes in patients, and fat redistribution with and without serum lipid abnormalities have been received.

Table 8. Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Table 9. Characteristics of protease inhibitors (PIs) 

Table. 10 Drugs that should not be used with protease inhibitors

Table 11. Drug interactions between protease inhibitors and other drugs; drug interactions requiring dose modifications

Table 13. Drugs Available Through Treatment Investigational New Drug Protocols 

20 Mar

Antiretroviral Therapy – Introduction – part2

Initiating Therapy in the Patient with Asymptomatic HIV Infection

Tables V and VI summarize the recommendations regarding when to initiate therapy and what regimens to use. In general, any patient with less than 500 CD4 + T cells/mm3 or greater than 10,000 (bDNA) or 20,000 (RT-PCR) copies of HIV RNA/ml of plasma should be offered therapy.

Table 5. Indications for the initiation of antiretroviral therapy in the chronically HIV-infected patient

Clinical Category

 

CD4+ T Cell Count and HIV RNA

 

Recommendation

 

Symptomatic (AIDS, thrush, unexplained fever) Any value Treat
Asymptomatic CD4+ T Cells <500/mm3
or

HIV RNA >10,000 (bDNA) or >20,000 (RT-PCR)
Treatment should be offered. Strength of recommendation is based on prognosis for disease-free survival as shown in Table IV and willingness of the patient to accept therapy.*
Asymptomatic CD4+ T Cells >500/mm3
and

HIV RNA <10,000 (bDNA) or <20,000 (RT-PCR)
Many experts would delay therapy and observe; however, some experts would treat

* Some experts would observe patients with CD4+ T cell counts between 350-500/mm3 and HIV RNA levels <10,000 (bDNA) or <20,000 (RT-PCR).

Table 6. Recommended  for treatment of established HIV infection

Preferred: Strong evidence of clinical benefit and/or sustained suppression of plasma viral load (2,42,43) One choice each from column A and column B. Drugs are listed in random, not priority, order:

Column A Column B
(AI) ZDV + ddI (AI)
Nelfinavir (AII) d4T + ddI (AII)
Ritonavir (AI) ZDV + ddC (AI)
SGC* (AII) ZDV + 3TC# (AI)
Ritonavir +
Saquinavir SGC or HGC (BII)
d4T + 3TC# (AII)
Efavirenz (AII)
Alternative: Less likely to provide sustained virus suppression or data inadequate (44,45).

Nevirapine or delavirdine + 2 NRTIs (Column B, above)***(BII)

Not generally recommended: Strong evidence of clinical benefit but initial virus suppression is not sustained in most patients (46-49).

2 NRTIs (Column B, above)(CI) Saquinavir-HGC + 2 NRTIS (Column B, above)II(CI)

Not recommended: Evidence against use, virologically undesirable, or overlapping toxicities

All monotherapies ##(DI)
d4T + ZDV (DI)
ddC +ddI ### (DII)
ddC +d4T ### (DII)
ddC + 3TC (DII)

* Virologic data and clinical experience with saquinavir-SGC (Fortovase) are limited in comparison with other protease inhibitors.

** Use of ritonavir 400 mg b.i.d. with saquinavir-SGC (Fortovase) 400 mg b.i.d. results in similar drug exposure and activity as when using 400 mg b.i.d. of saquinavir-HGC (Invirase) in combination with ritonavir. However, this combination with Fortovase has not been extensively studied, and gastrointestinal toxicity may be greater when using Fortovase. 

*** The combination of any of the 3 available NNRTIs + 2 NRTIs can suppress viremia to undetectable levels in the majority of patients remaining on treatment for > 28 weeks. An efavirenz- containing regimen has been shown to compare favorably to a PI-containing regimen with regard to suppression of viremia through 36 weeks; such head-to-head comparative trials have not been performed with nevirapine or delavirdine. Of note, use of efavirenz, nevirapine or delavirdine may result in resistance that precludes efficacy of any other member of this drug class. 

# High-level resistance to 3TC develops within 2- 4 weeks in partially suppressive regimens; optional use is in 3-drug antiretroviral combinations that reduce viral load to undetectable levels. P Use of saquinavir-HGC (Invirase) is generally not recommended, except in combination with ritonavir. 

## Zidovudine monotherapy may be considered for prophylactic use in pregnant women with low viral load and high CD4 + T cell counts to prevent perinatal transmission, as discussed under 

### This combination of NRTIs is not recommended based on lack of clinical data using the combination and/or overlapping toxicities.

Comparison of the results obtained from the RT-PCR and bDNA assays using the manufacturer’s controls consistently indicate that the HIV-1 RNA values obtained by RT-PCR are approximately two times higher than those obtained by the bDNA assay (12). Thus, the MACS values must be multiplied by approximately 2 to be consistent with current RT-PCR values. A third test for HIV RNA, the Nucleic-Acid Sequence Based Amplification (NASBA), is currently used in some clinical settings.

When initiating therapy in the patient naïve to antiretroviral therapy, one should begin with a regimen that is expected to reduce viral replication to undetectable levels. Based on the weight of experience, the preferred regimen to accomplish this is 2 nucleoside analogues (NRTIs) and one potent protease inhibitor (Pl); however, recent data with the use of efavirenz (an NNRTI) in place of the PI may support such a substitution (Table VI). Alternative regimens have been employed; these include ritonavir and saquinavir (with one or two nucleoside analogues) or nevirapine as a substitute for the protease inhibitor. Ritonavir and saquinavir (hard gel capsule) dual PI therapy (without an NRTI) appears to be potent in suppressing viremia below detectable levels, and has convenient BID dosing. At least one additional NRTI be used when the physician elects to use 2 PIs as initial therapy. Using 2 NRTIs alone does not achieve the goal of suppressing viremia to below detectable levels as consistently as does combination treatment with 2 NRTIs and a PI and should be used only if more potent treatment is not possible.  Online Canadian Pharmacy

18 Mar

Antiretroviral Therapy – Introduction – part1

Antiretroviral treatment should be offered to all patients with the acute HIV syndrome, those within six months of seroconversion, and all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy in asymptomatic patients depend on virologic and immunologic factors. In general, treatment should be offered to individuals with fewer than 300 CD4 + T cells/mm3 or plasma HIV RNA levels exceeding 10,000 copies/ml (bDNA assay) or 20,000 copies/ml (RT-PCR assay). Once the decision has been made to initiate antiretroviral therapy, the goal is maximum viral suppression for as long as possible. Results of clinical trials to date indicate that this may currently be best achieved with a potent protease inhibitor (PI) in combination with two nucleoside analogue reverse transcriptase inhibitors (NRTIs). Another option is the combination of saquinavir plus ritonavir combined with one or two NRTIs. Results of therapy are evaluated primarily with plasma HIV RNA levels; these are expected to show a one log (10 fold) decrease at eight weeks and no detectable virus (<500 copies/ml) at 4-6 months after initiation of treatment. Failure of therapy (i.e., plasma HIV RNA levels exceeding 500 copies/ml) at 4-6 months may be ascribed to non-adherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, or resistance Patients whose therapy fails should change to at least two new agents that are not likely to show cross-resistance with drugs given previously; ideally, the regimen should be changed to a completely new regimen devoid of anticipated cross-resistance and with clinical trial data supporting a high probability of viral response.

Introduction

Use of Testing for Plasma HIV RNA Levels and CD4 + T Cell Count in Guiding Decisions for Therapy

Decisions regarding initiation or changes in antiretroviral therapy should be guided by monitoring the laboratory parameters of plasma HIV RNA (viral load) and CD4 + T cell count, as well as the clinical condition of the patient. Measurement of plasma HIV RNA levels (viral load), using quantitative methods, should be performed at the time of diagnosis and every 3–4 months thereafter. Plasma HIV RNA levels should also be measured immediately prior to and again at 2–8 weeks after initiation of antiretroviral therapy. This second time point allows the clinician to evaluate the initial effectiveness of therapy, since in most patients adherence to a regimen of potent antiretroviral agents should result in a large decrease (~0.5 to 0.75 log10) in viral load by 2–8 weeks.

Once the patient is on therapy, HIV RNA testing should be repeated every 3–4 months to evaluate the continuing effectiveness of therapy. With optimal therapy viral levels in plasma at 6 months should be undetectable, that is, below 500 copies of HIV RNA per ml of plasma. If HIV RNA remains detectable in plasma after 6 months of therapy, the plasma HIV RNA test should be repeated to confirm the result and a change in therapy should be considered. Plasma HIV RNA levels should not be measured during or within four weeks after successful treatment of any intercurrent infection, resolution of symptomatic illness, or immunization. Because there are differences among commercially available tests, confirmatory plasma HIV RNA levels should be measured by the same laboratory using the same technique in order to ensure consistent results. Buy Generic Viagra

A minimally significant change in plasma viremia is considered to be a 3-fold or 0.5 log10 increase or decrease. A significant decrease in CD4 + T lymphocyte count is a decrease of >30% from baseline for absolute cell numbers and a decrease of >3% from baseline in percentages of cells.

Established Infection

Patients with symptomatic disease (wasting, thrush or unexplained fever for > 2 weeks) including AIDS should be offered antiretroviral therapy.

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