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Journal of Cancer Research and Therapeutics
Medknow Publications on behalf of the Association of Radiation Oncologists of India (AROI)
ISSN: 0973-1482 EISSN: 1998-4138
Vol. 6, Num. 4, 2010, pp. 432-441

Journal of Cancer Research and Therapeutics, Vol. 6, No. 4, October-December, 2010, pp. 432-441

Review Article

AIDS: A radiation oncologist's perspective

Suman Mallik, Kaustav Talapatra, Jyotirup Goswami

Department of Radiation Oncology, Centre for Cancer, Kokilaben Dhirubhai Ambani Hospital and Research Institute, Four Banglows, Andheri (W), Mumbai - 400053, Maharashtra, India

Correspondence Address: Suman Mallik, Department of Radiation Oncology, Centre for Cancer, Kokilaben Dhirubhai Ambani Hospital and Research Institute, Four Banglows, Andheri (W), Mumbai - 400053, Maharashtra, India, malliksuman@gmail.com

Code Number: dv10112

PMID: 21358076

DOI: 10.4103/0973-1482.77078

Abstract

While HIV is often associated with tuberculosis and a number of opportunistic infections, the spectrum of diseases of patients with HIV infection encompasses a number of malignancies as well. Typically, these are the AIDS-defining malignancies, though other malignancies also comprise a significant caseload. Radiotherapy plays an integral part in anti-cancer treatment and its tolerance and efficacy in HIV+ patients are therefore important. The patient's level of immunity as manifested by the CD4 count has a significant bearing on treatment outcomes. In some cases, like primary central nervous system lymphoma (PCNSL), the occurrence of the malignancy itself is tied to the patient's immunity with increased incidence in patients with CD4 counts less than 50/mm ³ . The success of highly active antiretroviral therapy (HAART) has allowed administration of standard doses of radiotherapy and even chemotherapy in recent times leading to improved outcomes. In general, standard radiotherapy and concomitant chemo-radiotherapy protocols should be used wherever possible, so as not to compromise disease control. Local control and disease-specific survival rates in HIV patients are no worse than in HIV? patients, but this is only true for CD4 counts above 200/mm ³ . In certain situations like cervical intraepithelial neoplasia CIN, HAART itself is associated with disease regression. The question of increased radiosensitivity in HIV patients remains unresolved in most diseases and there are sparse data with regard to non-HIV associated malignancies in these patients. Greater caution and emphasis on good supportive care and HAART would appear to be essential when treating the malignancies in HIV+ patients with standard anti-cancer regimens.

Keywords: AIDS, malignancy, radiotherapy, toxicity

Introduction

There are 33.4 million individuals estimated to be living with HIV, (WHO, 2008, http://www.who.int/hiv/data ) of whom around 2.7 million are newly infected every year with around 2.0 million estimated deaths annually of which more than 0.28 million are below 15 years. Prevalence of adult HIV in India is 0.3% (WHO 2007, apps.who.int/globalatlas). In 2001, the estimation was that in spite of the overall prevalence of HIV being 0.5%, due to the population size, in terms of numbers, it was second only to South Africa as far as people living with HIV/AIDS were concerned.

We have explored the issues of radiotherapy and HIV related malignancies based on available evidence to answer the optimal radiotherapeutic management in HIV+ patients with malignancies, especially in AIDS related malignancies [Table - 1].

Search strategy

Data of this review were identified by searches of Medline, current contents, PubMed, Embase, Cancer Lit, Aidsline using the search terms "AIDS and radiotherapy", "HIV and malignancies", "HIV and cancer cervix", "HIV and anal and cancer", "HIV and lymphoma", "HIV and NHL", "HIV and Hodgkin′s disease", "HIV and PCNSL", "HIV and Kaposi′s sarcoma", "Kaposi′s and radiotherapy", "HIV and squamous carcinoma of conjunctiva", "HIV and leiomyosarcoma", "HIV and radiotherapy and toxicity", "HAART and radiotherapy", "HIV and radiotherapy and head-neck cancer, "HIV and breast cancer", "HIV and testicular cancer", and "HIV and lung cancer". Only papers published in English between 1974 and 2010 have been included.

Aids and Carcinoma Cervix

Incidence of cervical cancer is increasing with the incidence of HIV infection. Both HIV-1 and HIV-2 are associated with higher risk of cervical cancer. ^[2] Cervical cancer and HIV infection share similar etiology. In 1993, Centre for Disease Control (CDC) has included carcinoma cervix as an AIDS defining illness. ^[3],[4] Women with HIV-1, HIV-2, and HIV-1 and HIV-2 dual infection were all at increased risk of prevalent high grade squamous intraepithelial lesions HSIL s or invasive cervical cancer (ICC), compared with HIV women. Hawes et al. have reported that high grade squamous intraepithelial lesions are more common in HIV-2 infection compared to HIV-1, whereas low risk intraepithelial lesions are more common in HIV-1. Dual infection increases the incidence of low grade squamous intraepithelial lesion (LSIL) and HSIL significantly. ^[5] Human papilloma virus (HPV) (16, 18, 31, 33, 35, 45, 52, 53, 58 and 66) coinfection is associated with an increased risk of developing intraepithelial neoplasia and rapid progression to invasive cervical cancer. ^{[5],[6],[7],[8],[9],[10]} About 20% cases of CIN in HIV+ patients is associated with HPV infection. ^[11] Risk of squamous intraepithelial lesion is increased by 4.5 times in HIV-infected patients. Coinfection of HPV with HIV is thought to result in cell disruption, and consequently, dysregulation of the cellular and hormonal arms of local and systemic immunity, resulting in the inability to contain infection and disease progression. ^{[12],[13],[14]} Recurrence of CIN after treatment is more common in HIV+ women compared to HIV-ones (62% vs. 18%). Women with CD4 cell counts <200 per μl have a twofold increase in both prevalence and incidence of squamous intraepithelial lesion (SIL) compared with women with CD4 cell counts ≥200 per μl. HIV-1, HIV-2, dual infection, CD4 level, and HIV viral load have significantly increased the risk of having ICC and CIN.

Treatment

Highly active antiretroviral therapy (HAART) is an integral part of therapy of HIV+ women with cervical cancer. SIL can regress with the use of HAART, and the rate of regression of lesion is more with the use of HAART. ^[15] International Atomic Energy Association (IAEA) has developed a guideline for treatment of HIV associated cervical cancer depending on CD4 counts.

IAEA TECDOC guideline

Patients with intact immune system: CD4 > 200 per μl

No evidence that customary management needs to be changed

Patients with moderate immune impairment: CD4 > 50 but <200 per μl

Standard management approach but with caution (intolerance and infection)

Patients with severe immune impairment: CD4 < 50 per μl

Palliative fractionation

Chance of occurrence of enhanced radiation toxicity is the most concerning factor for an oncologist. The increased toxicity is due to inherent radiosensitivity and glutathione deficiency. ^[16],[17]

Shrivastava et al. have shown in their series of HIV+ carcinoma cervix patients that only 12 out of 32 patients could complete the full course of radiation including brachytherapy. Out of these 12 cases, 11 experienced complete response. This means response of the disease to treatment is almost same as with non-seropositive patients but the challenge is to complete the treatment and choose the modalities judiciously. ^[18],[19]

Aids and Anal Canal Carcinoma

Anal canal carcinomas are rare form of disease comprising 4% of malignancies of lower gastrointestinal tract. It is the disease of middle-aged adults, with female sexual preponderance. The incidence is much higher in men who practice anal receptive intercourse and those who are HIV+.

A population study conducted in Denmark has shown the risk factors to be more than 10 sex partners (RR = 2.5), anal wart (RR = 11.7) and anal intercourse before the age 30 (RR = 3.4), while 88% patients were positive for HPV DNA. ^[20] Anal canal cancers are considered as a sexually transmitted disease. ^{[21],[22],[23]}

HIV+ male homosexuals have increased risk of having anal intraepithelial neoplasia (AIN), the precursor of squamous cell carcinoma. ^[24] Contrary to cervical cancer, SIL of anal canal and anal intraepithelial neoplasia do not regress with HAART. ^[25] Based on two large randomized studies on anal cancer, united kingdom coordinating committee on cacer research (UKCCR) and European organization for research and treatment of cancer (EORTC ), standard of care of anal canal cancer is chemoradiation using 5-fluorouracil (5-FU) and mitomycin C (MMC). ^{[26],[27],[28],[29]}

Toxicity due to intensive chemoradiation is the primary concern for HIV+ anal cancer. In pre-HAART era, side effects were more frequent and poorer outcome was associated with combined chemoradiation. ^{[30],[31],[32],[33],[34],[35],[36]}

Hoffman et al. compared two groups of patients based on CD4 count (>200 per μl vs. <200 per μl), treated with concomitant chemoradiation. Nine patients had CD4 count >200 per μl and eight patients had the count <200 per μl. Both groups experienced excellent response (100 and 87%, respectively), but grade 3 toxicities were higher (87% vs. 66%) in the group with lesser CD4 count. ^[37]

Cleator et al. treated 12 HIV+ anal carcinoma patients with concomitant chemoradiation (5-FU + MMC) and achieved 82% complete response with 45% grade 3 toxicity. ^[38] Similarly, Edelman et al. treated 17 HIV+ patients of anal carcinoma with routine chemoradiation protocol (5FU + MMC + Radio Theropy (RT) up to 50.4 Gy). They reported 82% complete response rate with 67% actuarial survival at 18 months; 47% experienced severe skin toxicity and 53% experienced severe hematologic toxicity. ^[39]

Christopher et al. did a match pair comparison of 10 HIV+ anal carcinoma patients who were on HAART with 10 HIV− patients using concomitant chemoradiation schedule. Though complete response rate was 100% in HIV+ patients, local control was inferior compared to HIV− patients at 44 months (P = 0.03). Inferior local control did not reflect on overall survival (OS) which was comparable at 5 years (70% vs. 69%) in spite of having comorbidities. Acute chemoradiation toxicity was higher in HIV+ cohort, but there was no difference in late toxicity. ^[40]

Vatra et al. retrospectively analyzed clinical data of 20 HIV+ patients with 24 HIV− patients. Clinical response, remission rate and 3 months mortality were better in HIV+ arm. In this series, less number of patients in HIV+ group received chemotherapy compared to those in HIV− one. ^[32]

In a recently published report, Yuji Seo et al. compared 19 consecutive immunocompetent patients with 17 immunodeficient (14 were HIV+) patients of anal canal carcinoma treated with chemoradiation protocol. With a median follow-up of 3.1 years, there were no differences in OS, disease specific survival and colostomy free survival. ^[41]

As there is no hard evidence that the tumor control is worse with chemoradiation and chemoradiation can cause progression of AIDS, HIV+ patients should be considered to be treated in a similar way as that of HIV− patients for anal cancer. Special precautions should be taken in HIV+ patients to prevent or to support toxicity especially with CD4 count <200 per μl.

AIDS and Kaposi′s Sarcoma

Before the advent of HAART, the incidence of Kaposi′s sarcoma (KS) was 20,000 times higher in patients with AIDS than in the general population. ^[42] Moriz Kaposi in 1872 first described the disease as "sarcoma idiopathicum multiple haemorrhagicum". Later, in 1912, Sternberg termed the disease as "Kaposi′s Sarcoma" (KS). In 1981, the epidemic form was first described by Hymes. ^[43] Epidemic form is caused by HHV-8 (KSHV) . It is common in homosexual men and is the most frequent neoplasm in AIDS patients. In HIV+ patients, the clinical presentation varies from very early signs and symptoms to very extensive growth. Papular and macular lesions appear in the skin, most commonly at feet, legs, face, genitalia or they may be exophytic in advanced cases. These may be associated with lymphedema. Extracutaneous spread is common in patients not undergoing HAART. ^[44]

Classically, KS is classified into four types: i) endemic KS, ii) classical KS, iii) pediatric (lymphadenopathic) KS and iv) epidemic (AIDS related) KS. KS is further classified into two risk groups based on prognosis [Table - 2]. ^[45]

HAART is one of the integral components of treatment of epidemic KS. It inhibits HIV replication, diminished production of HIV-1 transactivating protein, inhibits angiogenic activity and ameliorates immune response against KSHV/HHV8. ^{[46],[47],[48],[49],[50],[51]}

Different chemotherapeutic agents have been proved to be beneficial, especially in widespread disease, and these include liposomal doxorubicin, paclitaxel, vincristine, vinblastine and bleomycin. ^{[52],[53],[54],[55],[56],[57],[58],[59],[60],[61]}

Apart from chemotherapeutic agents, immunotherapy with interferon alpha is useful in immunocompetent patients with CD4 count >200 per μl. Antiangiogenic agents like thalidomide and tyrosine kinase inhibitors also have been used with some success. ^{[62],[63],[64],[65],[66],[67]}

Local therapy of KS includes radiotherapy, intralesional chemotherapy, cryotherapy and photodynamic therapy. Superficial therapies with orthovoltage X-ray or electron beam therapy are useful to achieve response and symptom palliation. ^{[42],[44],[68],[69],[70],[71],[72],[72],[73],[74],[75],[76],[77]}

In a retrospective study at University of Mondor, 643 patients with KS were treated by radiation therapy at doses ranging from 10 to 30 Gy by 45-70 KV X-ray or 4 MV photon. They achieved good palliation of symptoms with response rate of 92% for cutaneous KS, 100% for oral epidemic Kaposi′s sarcoma EKS , 89% for eyelids, conjunctiva and genitals. ^[70]

Stelzer et al. treated 14 patients with 71 lesions in three dose schedules: 20 Gy in 10 fractions, 40 Gy in 20 fractions and 8 Gy in single fractions. Complete response rate was higher in 20 and 40 Gy groups compared to 8 Gy group with hazard ratio (HR) of 1.58 (95% CI 1.01-2.48) and 1.65 (95% CI 1.06-2.57), respectively, but on the other hand, adverse events were more in higher dose groups (20 and 40 Gy) with HR 3.67 (95% CI 1.17-11.52) and 7.65 (2.65-22.13), respectively. ^[78],[79]

In a randomized controlled trial, Singh et al. compared two dose fractionation schedules for cutaneous EKS: 24 Gy in 12 fractions and 20 Gy in 5 fractions in a total of 60 patients. Age (P = 0.05), stage (P = 0.02), associated systemic illness (P = 0.0024) and Stage I (P = 0.0024) had impact on OS. Patients who received 20 Gy in 5 fractions had a better local control compared to the ones who received 24 Gy in 12 fractions arm, though not statistically significant (Median 455 days and 150 days, respectively, with P = 0.1). There were also no significant differences in toxicity. ^[80]

AIDS and Lymphoma

The incidence of non-Hodgkin′s lymphoma (NHL) has increased significantly with the AIDS epidemic, in that 2-3% of newly diagnosed AIDS cases are of NHL. ^[1],[81]

AIDS related lymphomas comprise B-cell tumors of aggressive type which include diffuse large B-cell lymphoma, B-cell immunoblastic lymphoma, Burkitt or Burkitt-like lymphoma.

The HIV-associated lymphomas can be categorized into:

aggressive B-cell lymphoma,
primary central nervous system lymphoma (PCNSL),
primary effusion lymphoma,
Hodgkin lymphoma, and
plasmablastic multicentric Castleman disease.

Before HAART era, reduced dose chemotherapy was the dictum for HIV associated NHL due to poor tolerability to chemotherapy. Along with HAART, unacceptable toxicity can be avoided even with standard dose chemotherapy. ^{[82],[83],[84]}

Before HAART, similar to chemotherapy, radiotherapy was also associated with higher toxicity. Post HAART era radiotherapy data are meager.

AIDS and Hodgkin′s Lymphoma

Although there have been multiple reports of Hodgkin′s lymphoma in association with AIDS in the last two decades, Hodgkin′s still does not form a part of the CDC definition. HIV related Hodgkin′s lymphoma presents in an aggressive fashion, often with bone marrow involvement or extranodal presentation. ^{[1],[85],[86],[87],[88]}

AIDS and PCNSL

Before the onset of HIV, primary CNS lymphoma was a rare entity. PCNSL occurs in patients with severe immunodeficiency and most of them are of B cell origin. ^{[89],[90],[91],[92]}

75% of PCNSL develops in patients who already have AIDS and most commonly in severely immunocompromised (50% with CD4 <50/dl) individuals. PCNSL manifests clinically in 2-6% of AIDS patients and 12% in autopsy. Affected persons usually present with features of intracranial space occupying lesions like cognitive dysfunction, psychomotor slowing, personality changes, disorientation, features of raised intra cranial tensionICT , cranial nerve palsy and hypothalamic dysfunction. Microscopically, it shows angiogenic growth pattern. Tuft of tumor cells are found within and around cerebral blood vessels and split the blood vessel wall. Elevated levels of immunoglobulins recognized by a V4-34 gene segment encoded antibody have been reported in association with Epstein Barr virus (EBV) infection. EBNA-2 and LMP-1 contribute to malignant transformation at various levels. EBV-DNA in CSF by polymerase chain reaction (PCR) is highly specific for PCNSL in AIDS and a reliable marker for monitoring response to therapy. PCNSL is associated with HHV8 and HHV6 infections.

Initial approach for treatment of PCNSL was cranial RT only. Several studies have reported of improvement of survival with addition of RT. ^{[93],[94],[95]}

RT alone in PCNSL has low cure rate and high local recurrence rate. Though PCNSL resembles extranodal NHL pathologically, it behaves more aggressively from a radiotherapeutic viewpoint. ^{[96],[97],[98],[99]}

PCNSL relapses frequently with only RT and has a median survival of only 12-18 months and a 5-year survival of <5-10% . ^[100]

Multimodal treatments have been introduced by DeAngelis et al., including radiotherapy, chemotherapy and steroids. Though their study was nonrandomized, the impact of RT in combination with high-dose methotrexate and steroids was so obvious (median survival 44 months) that it has been widely accepted as the treatment of choice. ^[101],[102]

In DeAngelis protocol, whole brain radiotherapy is started after few cycles of high-dose methotrexate and is followed by steroid and high-dose ara-C. RT consists of whole brain radiotherapy of 40 Gy followed by tumor boost of 15.4 Gy. A small retrospective study by Shibamoto and colleagues suggested that whole brain radiotherapy is required for treatment of PCNSL. As in this study, 83% patients experienced recurrence out of field in the small field group compared to 22% in the group with wider margin (<4 cm vs. >4 cm). ^[103]

There is no strong evidence of dose escalation of RT for treatment of PCNSL. In an RTOG phase II study, a total of 60 Gy (40 Gy whole brain + 20 Gy to gross tumor with 2 cm margin) was prescribed to gross tumor with 2 cm margin. With a median survival of 19 months, 61% recurrences occurred at the boost region and there was no clear dose response over 40 Gy.

Combination of radiotherapy along with high-dose methotrexate has got a significant adverse effect in the form of leukoencephalopathy, which has been reported. ^[104],[105]

Bessel et al. assessed the effect of reduced dose radiotherapy in patients with PCNSL, receiving CHOD/BVAM (cyclophosphamide, doxorubicin, vincristine, methotrexate, dexamethasone/carmustine, vincristine, methotrexate, cytarabine) regimen. In one group, 31 patients received 45 Gy standard whole brain RT, and in the second one, 26 patients received 30.6 Gy dose if there was complete response to chemotherapy. Three-year relapse risk was higher in lesser dose group (25% vs. 83%, P = 0.01). Treatment modality was the only predictor of relapse. Age more than 60 years showed a negative impact on OS in multivariate analysis. RT dose was an important predictor of OS in patients younger than 60 years (3-year OS: 92% vs. 60% for patients receiving 45 and 30.6 Gy, respectively; P = 0.04). So, reduction of dose of RT even after achieving complete response (CR) after chemotherapy has increased risk of recurrence. ^[106]

Newell et al. retrospectively reviewed 111 patients of HIV related PCNSL. Median survival was only 50 days (range 4-991 days). Patients who received HAART (P = 0.01) and/or radiotherapy (P = 0.0001) showed improved survival. Those who received radiotherapy of more than 30 Gy dose showed a favorable outcome. Poor performance status and encephalopathy predicted shorter survival duration. Other important predictors were CD4 count (≤125 vs. >125, P = 0.03) and performance status [Eastern Cooperative Oncology Group (ECOG ≤ 2 vs. 3, P = 0.04)]. ^[107]

Three hundred and thirty-eight consecutive PCNSL patients were analyzed at Memorial Sloan Kettering Cancer Centre between 1983 and 2003. On multivariate analysis, age and performance status were the only significant predictors of survival. Based on the multivariate data, they stratified their patients into three recursive partitioning analysis groups [Table - 3]. ^[108]

To reduce the RT related toxicity, options of reduction of RT dose have been evaluated. After the advent of HAART, long-term survival in PCNSL in HIV+ is not uncommon. Combined HIV, RT and chemotherapy related leukoencephalopathy is of greater concern. Sequencing of chemotherapy with radiotherapy has not been standardized yet in HIV associated PCNSL. But for younger patients with good CD4 count and good performance status, standard approach is justified though there is no strong evidence of that in HIV+ patients.

Squamous Carcinoma of Conjunctiva

It is a type of ocular surface squamous neoplasia (OSSN). OSSN is the most common ocular surface tumor in HIV infected individuals in Africa. The spectrum varies from noninvasive (CIN) to invasive forms. It is associated with HPV and HIV infections. Incidence of squamous cell carcinoma of conjunctiva (SCCC) is increasing because of the spread of HIV infection. ^{[109],[110],[111]}

In a case control study, Ateenyi Agaba et al. have shown that out of 94 patients of SCCC, 79 suffered from HIV, and cutaneous HPV was detected in 45% of cases. Most common types of HPV were 5 and 8. ^[112]

Apart from these two, other HPV types like 19-25 and 36-38 are associated with SCCC, but not 16 and 18. ^[113] Primary management of SCCC is surgical resection. ^[114] Adjuvant radiation therapy has shown some benefit. Radiotherapy is delivered by beta rays (strontium applicator),, brachytherapy or superficial X-rays. ^{[115],116],[117]}

In an adjuvant setting, 25-40 Gy dose is delivered. Usually, this superficial therapy is well tolerated and the control rate is around 97%. ^[116]

HIV and Non-HIV Associated Malignancies

Radiotherapy tolerance for standard doses of radiotherapy in HIV-infected patients with prostate cancer is the same as in non-HIV infected patients. ^{[118],[119],[120],[121]}

Lung cancer is the non-HIV associated malignancy with highest incidence in HIV-infected patients compared to normal population. ^[122],[123] Data suggest a higher chance of severe esophagitis in HIV-infected lung cancer patients on radiotherapy. ^{[124],[125],[126],[127]} HAART has modest survival benefit in early stage lung cancer patients, but not in patients with advanced stage disease. ^[128],[129]

There are little data available on radiotherapy in non-KS head and neck malignancies in HIV patients. Whatever little is available suggests that tolerance to standard doses is the same as the general population. ^[130],[131]

Patients with testicular seminoma have in general tolerated standard doses of radiotherapy well. ^{[132],[133],[134],[135],[136]} Breast cancer patients, in general, have tolerated standard doses of radiotherapy well, but not chemotherapy, though the data are quite sparse. ^{[137],[138],[139]}

Data on disease control and toxicity for colorectal cancer patients with HIV treated by radiotherapy are frankly inconclusive. ^{[140],[141],[142]}

Per se, local control and disease-specific survival rates in HIV patients are no worse than HIV− patients, but this is only true, in general, for patients with higher CD4 counts (above 200/mm ³ ). ^[143]

HIV and Radiotherapy Toxicities

The question of increased radiosensitivity in HIV patients remains unresolved in most diseases, barring KS and PCNSL in the pre-HAART era. Most of the other AIDS-defining malignancies such as cervical and anal carcinomas can be safely treated by standard dose chemo-radiotherapy. ^[143] There are sparse data with regard to non-HIV associated malignancies in these patients. The idea that lower CD4 counts correlate with worse skin/mucosal/GU/GI toxicities has been challenged. ^{[37],[38],[39],[144],[145]}

Conclusion

HIV is associated with a wide spectrum of malignancies and pre-malignant conditions. The patient′s level of immunity as manifested by the CD4 count has a significant bearing on treatment outcomes. In some cases, like PCNSL, the occurrence of the malignancy itself is tied to the patient′s immunity with increased incidence in patients with CD4 counts less than 50/mm ³ . The success of HAART has allowed administration of standard doses of radiotherapy and even chemotherapy in recent times, leading to improved outcomes. In general, standard radiotherapy and concomitant chemo-radiotherapy protocols should be used wherever possible, so as not to compromise disease control. Per se, local control and disease-specific survival rates in HIV patients are no worse than in HIV− patients, but this is only true for CD4 counts above 200/mm ³ . In certain situations like CIN, HAART itself is associated with disease regression. The question of increased radiosensitivity in HIV patients remains unresolved in most diseases and there are sparse data with regard to non-HIV associated malignancies in these patients. Greater caution and emphasis on good supportive care and HAART would appear to be essential when treating HIV+ patients of malignancies with standard anti-cancer regimens.

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