HAART Era Research Articles

Tuberculosis in HIV-infected patients in the HAART era

Summary Tuberculosis in one of the most common opportunistic infections in HIV infected patients. HIV promotes progression of Mycobacterium tuberculosis latent infection to active disease and in turn M tuberculosis enhances HIV replication. During eight year period 51 cases of tuberculosis was recognized in Department of Infectious Diseases and Hepatology in Bydgoszcz. Only 4 patients were on antiretroviral therapy and of those who never received antiretroviral treatment; 70% had a CD4 count >100 cells/ml at the time of tuberculosis, and the high proportion (25.4%) of patients were diagnosed with HIV infection concurrently with tuberculosis. Diagnosis was confirmed by isolation of Mycobacterium tuberculosis and by the detection of nucleic acids of pathogen in 96.1% patients. The sputum smear was positive only in 5 cases of pulmonary tuberculosis and in three cases of disseminated tuberculosis was the most common clinical manifestation of disease in study population. A total of 8 patients with pulmonary involvement the chest radiograph examination was normal. Tuberculosis in HIV infected patients is in spite of availability of antiretroviral therapy a serious medical and epidemiological problem.

Declines in Mortality Rates and Changes in Causes of Death in HIV-1-Infected Children During the HAART Era

Introduction of highly active antiretroviral therapy has significantly decreased mortality in HIV-1-infected adults and children. Although an increase in non-HIV-related mortality has been noted in adults, data in children are limited. To evaluate changes in causes and risk factors for death among HIV-1-infected children in Pediatric AIDS Clinical Trials Group 219/219C. Multicenter, prospective cohort study designed to evaluate long-term outcomes in HIV-1-exposed and infected US children. There were 3553 HIV-1-infected children enrolled and followed up between April 1993 and December 2006, with primary cause of mortality identified in the 298 observed deaths. Mortality rates per 100 child-years overall and by demographic factors; survival estimates by birth cohort; and hazard ratios for mortality by various demographic, health, and antiretroviral treatment factors were determined. Among 3553 HIV-1-infected children followed up for a median of 5.3 years, 298 deaths occurred. Death rates significantly decreased between 1994 and 2000, from 7.2 to 0.8 per 100 person-years, and remained relatively stable through 2006. After adjustment for other covariates, increased risk of death was identified for those with low CD4 and AIDS-defining illness at entry. Decreased risks of mortality were identified for later birth cohorts, and for time-dependent initiation of highly active antiretroviral therapy (hazard ratio 0.54, P < 0.001). The most common causes of death were "End-stage AIDS" (N = 48, 16%) and pneumonia (N = 41, 14%). The proportion of deaths due to opportunistic infections (OIs) declined from 37% in 1994-1996 to 24% after 2000. All OI mortality declined during the study period. However, a greater decline was noted for deaths due to Mycobacterium avium complex and cryptosporidium. Deaths from "End-stage AIDS," sepsis and renal failure increased. Overall death rates declined from 1993 to 2000 but have since stabilized at rates about 30 times higher than for the general US pediatric population. Deaths due to OIs have declined, but non-AIDS-defining infections and multiorgan failure remain major causes of mortality in HIV-1-infected children.

Early development of non-hodgkin lymphoma following initiation of newer class antiretroviral therapy among HIV-infected patients - implications for immune reconstitution

BackgroundIn the HAART era, the incidence of HIV-associated non-Hodgkin lymphoma (NHL) is decreasing. We describe cases of NHL among patients with multi-class antiretroviral resistance diagnosed rapidly after initiating newer-class antiretrovirals, and examine the immunologic and virologic factors associated with potential IRIS-mediated NHL.MethodsDuring December 2006 to January 2008, eligible HIV-infected patients from two affiliated clinics accessed Expanded Access Program antiretrovirals of raltegravir, etravirine, and/or maraviroc with optimized background. A NHL case was defined as a pathologically-confirmed tissue diagnosis in a patient without prior NHL developing symptoms after starting newer-class antiretrovirals. Mean change in CD4 and log10 VL in NHL cases compared to controls was analyzed at week 12, a time point at which values were collected among all cases.ResultsFive cases occurred among 78 patients (mean incidence = 64.1/1000 patient-years). All cases received raltegravir and one received etravirine. Median symptom onset from newer-class antiretroviral initiation was 5 weeks. At baseline, the median CD4 and VL for NHL cases (n = 5) versus controls (n = 73) were 44 vs.117 cells/mm3 (p = 0.09) and 5.2 vs. 4.2 log10 (p = 0.06), respectively. The mean increase in CD4 at week 12 in NHL cases compared to controls was 13 (n = 5) vs. 74 (n = 50)(p = 0.284). Mean VL log10 reduction in NHL cases versus controls at week 12 was 2.79 (n = 5) vs. 1.94 (n = 50)(p = 0.045).ConclusionsAn unexpectedly high rate of NHL was detected among treatment-experienced patients achieving a high level of virologic response with newer-class antiretrovirals. We observed trends toward lower baseline CD4 and higher baseline VL in NHL cases, with a significantly greater decline in VL among cases by 12 weeks. HIV-related NHL can occur in the setting of immune reconstitution. Potential immunologic, virologic, and newer-class antiretroviral-specific factors associated with rapid development of NHL warrants further investigation.

Association of HIV Infection, Demographic and Cardiovascular Risk Factors With All-Cause Mortality in the Recent HAART Era

To determine the relationship of HIV infection, demographic, and cardiovascular disease (CVD) risk factors with mortality in the recent highly active antiretroviral therapy era. Vital status was ascertained from 2004 to 2007 in 922 HIV infected and 280 controls in the Study of Fat Redistribution and Metabolic Change in HIV infection; 469 HIV infected were included in analysis comparing HIV with similar age controls. Multivariable exponential survival regression (adjusting for demographic and CVD factors) estimated hazard ratios (HRs) for death. After 5 years of follow-up, the overall adjusted mortality HR was 3.4 [95% confidence interval (CI): 1.35-8.5]; HR was 6.3 among HIV infected with CD4 < 200 (95% CI: 2.2-18.2), 4.3 with CD4 200-350 (95% CI: 1.14-16.0), and 2.3 with CD4 > 350 (95% CI: 0.78-6.9). Among HIV infected, current smoking (HR = 2.73 vs. never smokers, 95% CI: 1.64-4.5) and older age (HR = 1.61 per decade, 95% CI: 1.27-2.1) were independent risk factors for death; higher baseline CD4 count was associated with lower risk (HR = 0.65 per CD4 doubling, 95% CI: 0.58-0.73). HIV infection was associated with a 3-fold mortality risk compared with controls after adjustment for demographic and CVD risk factors. In addition to low baseline CD4 count, older age and current smoking were strong and independent predictors of mortality in a US cohort of HIV-infected participants in clinical care.

Obstructive Lung Disease and Hiv/Aids in the Haart Era

Early in the AIDS epidemic opportunistic lung infections, most notably Pneumocystis infection, dominated the clinical picture and were the most common cause of death in HIV-infected individuals. With the progressive development of effective antiretroviral treatments and prophylaxis against Pneumocystis, the prognosis in HIV/AIDS has improved dramatically with median survival now greater than a decade. However, lung infections from opportunistic, as well as typical bacterial pathogens remain a major cause of morbidity and are still the leading cause of death from HIV/AIDS. In addition, as the survival of infected individuals has increased, it is becoming apparent that other more-chronic lung diseases, including emphysema and cancer, are more common in these individuals. Although the mechanisms by which HIV/AIDS increases the risk of both infectious and noninfectious lung diseases are still being investigated, there is emerging evidence from clinical and experimental studies that HIV causes oxidant stress within the airways and that this may render the airway epithelium more susceptible to damage from environmental stresses, such as tobacco smoke. In parallel, there is intriguing evidence that colonization of the lower airways with Pneumocystis may promote chronic airway inflammation and destruction even when there is no clinical evidence of overt infection. Therefore, an important manifestation of HIV/AIDS, even in the HAART era, may be chronic oxidative stress and inflammation within the airways, rendering these individuals more susceptible to a wider range of lung diseases than previously seen early in the epidemic. This article focuses primarily on the emerging association between HIV/AIDS and chronic obstructive pulmonary disease, a clinical entity that includes emphysema and chronic bronchitis, and summarizes some of the recent clinical and experimental evidence that implicates HIV/AIDS in the HAART era as a potent risk factor for this common and disabling lung disease.

HIV Related Hodgkin's Lymphoma in the HAART Era: A Comprehensive Review and Meta-Analysis of Response and Survival Rates.

Abstract 1652Poster Board I-678 IntroductionHodgkin lymphoma (HL) is one of the most common non-acquired immunodeficiency syndrome (AIDS)-defining tumors in human immunodeficiency virus (HIV)-infected patients. Studies have shown that HIV infected individuals have approximately a 7.5-fold (Goedert et al 1998) to nearly 13-fold increased risk for HL compared with the general population (Biggar et al. 2006, Engels 2006). The outcomes for patients with HL and HIV (HIV-HL) were described as inferior to HIV-negative patients. The existing literature regarding response and survival data is mainly comprised of small and/or retrospective studies. We reviewed the literature for the purpose of examining a larger HIV HL cohort for response rates and survival in the HAART era. MethodsWe searched PUBMED, OVID & Google Scholar (1980- July 2009) and ASH (2004-2008) & ASCO (2004-2009) Annual Meeting Abstracts. Key words used were ‘Hodgkin's Lymphoma', ‘Hodgkin's Disease',' HIV/AIDS', HAART, therapeutic outcomes, concomitant chemotherapy & HAART/antiretroviral therapy, non AIDS malignancies. Criteria for inclusion of studies were: 1) Upfront treatment of HL HIV infected patients with chemotherapy, with or without radiotherapy, with or without antiretroviral drugs/ HAART. 2) Reported in English 3) Studies with outcome measures of treatment for HIV-HL patients such as complete response (CR) rates, and/or at least one type of survival statistic. We also examined references from above articles as well as review articles, studies on pathogenesis & histologic features of HIV-HL, and epidemiologic studies for additional references. Studies that did not clearly report on a comprehensive cohort were excluded given increased probability of reporting bias. Primary outcome measures were CR rates, and 1- and 2-year overall survival rates. The data extracted included pre-treatment patient characteristics such as median age, sex, histological diagnosis, clinical staging, site of involvement, median CD4 cell counts, treatment regimen used, use or not of antiretrovirals/HAART & prophylactic agents with chemotherapy, response to treatment, toxicity, opportunistic infections, median follow up time, relapse, disease progression, death from treatment or infections. Summary CR and OS estimates were calculated based on the assumption of fixed effects and using the Mantel-Haenszel method. Results12 articles met inclusion criteria for meta-analysis of CR and/or OS. The overall CR rate was 72% (95% CI 67-77%) with 1- and 2-year OS of 78% (95% CI 73-82%) and 69% (95% CI 67-77%), respectively (Figure 1). Advanced stage was present in 63%, and histology other than nodular sclerosing in 76%. Mean baseline CD4 count was 212 (3-887); 59% of subject received HAART with chemotherapy. Death during treatment occurred in 7% and relapse was reported in 14%. ConclusionsAdverse baseline characteristics including advanced disease and histology other than NS persist in the HAART era. Response and survival rates are improved compared to pre-HAART era but remain lower than rates found in the HIV-negative population. Further prospective trials need to be done to examine improvements in treatment for this patient population. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Treating Hodgkin Lymphoma in HIV Positive Patients: a Comparative Analysis with the HIV Negative Population.

Abstract 3711Poster Board III-647 BackgroundHIV-associated Hodgkin Lymphoma (HIV-HL) has peculiar clinicopathologic features and less favourable outcome compared to HL of the HIV negative (neg) population. After the advent of HAART, HIV positive (pos) people seem to be at increased risk of HL than in first years of the epidemic; however, HIV-HL prognosis is expected to improve due to immunepreservation with HAART. Aim of the studyTo evaluate the chance of cure of HIV pos patients (pts) with HL, in comparison with the HIV neg population. Materials and methodsWe evaluated the proportion of pts who received treatment with curative intent and analysed the outcome in an intention to treat basis, in our series of consecutive HIV pos and neg pts with HL. Pts were excluded from curative treatment because of poor Performance Status (PS), major infections or severe comorbidities. Since 1997 all HIV pos pts received HAART during chemotherapy and thereafter. ResultsSince 1985 to Dec 1996 (pre-HAART period) we diagnosed 11 HIV-HL and from 1997 to Dec 2008 (HAART period) 29 HIV-HL. Median age was 39.5 ys (23-63). In the pre-HAART period we could treat with curative intent 7/11 pts (64%) with a complete remission (CR) rate of 43% and a median overall survival (OS) and progression free survival (PFS) of treated pts respectively 14 and 9 ms and 5y-OS and 5y-PFS both 28.5%. During the HAART period the proportion of treated pts was similar with 21/29 pts (72%) treated, the CR rate increased to 62% (versus 43% pre-HAART, P=NS) and the median OS and PFS of treated pts to 31 ms both (vs 14 and 9 ms pre-HAART, P=NS), with 5y-OS 35.4% and 5y-PFS 36%. According to the intention to treat, the OS of all pts was 6 ms pre-HAART (5y-OS 18.1%), and 16 ms in the HAART period (5y-OS 25.6%), with a follow-up of 37.5 ms (7-119). Median CD4 count at diagnosis was higher in the HAART period (213/cmm, range 15-648, vs 119/cmm, range 38-245, P=0.05), while no other significant differencies were seen in pts'characteristics between the two periods. During the HAART period 65% of pts were on HAART at lymphoma diagnosis; this proportion increased throughout the HAART era, from 57% between 1997-2002 to 73% between 2003-2008. The clinical features of HIV-HL showed a trend towards less aggressive disease from 1997-2002 to 2003-2008 (extranodal disease 64% and B symptoms 85% between 1997-2002 vs 42% and 53% between 2003-2008) and less drug abusers (71% vs 33%) and pts with previous AIDS-defining conditions (38% vs 22%). However, the proportion of pts we could treat remained low, 79% (1997-2002) and 67% (2003-2008). Between 1997-2002 most pts received Stanford V, while between 2003-2008 all pts received VEBEP. No pts died because of treatment toxicity. CR rate increased from 55% (1997-2002) to 70% (2003-2008) (P=NS) and the 3y-OS and 3y-PFS of treated pts from respectively 36.3% (median 20 ms) and 18.1% (median 7 ms) between 1997-2002 to 63.4% (P=NS) and 68.5% (P=0.05) between 2003-2008. The overall probability for survival, according to the intention to treat, did not significantly increased with 3y-OS 28.5% (median 9 ms) between 1997-2002 versus 42.3% (median 18 ms) between 2003-2008. The HIV-HL outcome, even in the recent years (2003-2008), remains unsatisfactory compared with a concomitant series of HIV neg pts. From Jan 2003 to Dec 2008 we diagnosed 144 HL in HIV neg subjects with less than 66 ys. All pts (100%) received therapy with curative intent, mostly ABVD, compared with 67% of HIV pos pts during the same period of time (P< 0.001). The CR rate was 90%, higher than in the concomitant series of HIV pos pts (70%) (P=0.05), as well as the probability of OS and PFS for pts receiving treatment (3y-OS 96.1% in HIV neg vs 63.5% in HIV pos pts, P<0.001, and 3y-PFS 79.7% in HIV neg vs 68.5% in HIV pos, P=NS). Relapse rate was 12% (15/126 pts) in the HIV neg pts, compared to 23% (3/13 pts) in the HIV pos group (P=NS). According to the intention to treat, the OS for all pts was strongly higher in the HIV neg group, with 3y-OS 96.1% compared to 42.3% in HIV pos pts (P<0.001). ConclusionsThough the outcome of HIV-HL has improved throughout the HAART era, in our single-Institution experience it remains significantly worse compared to the HIV neg population (lower CR and survival rates). Still a high proportion of pts cannot receive adequate treatment due to poor PS or comorbidities. Better control of HIV infection is advisable and specific treatment programs derived from the experience in the HIV negative setting seem warranted. Disclosures:No relevant conflicts of interest to declare.

The evolutionary rate dynamically tracks changes in HIV-1 epidemics: Application of a simple method for optimizing the evolutionary rate in phylogenetic trees with longitudinal data

Large-sequence datasets provide an opportunity to investigate the dynamics of pathogen epidemics. Thus, a fast method to estimate the evolutionary rate from large and numerous phylogenetic trees becomes necessary. Based on minimizing tip height variances, we optimize the root in a given phylogenetic tree to estimate the most homogenous evolutionary rate between samples from at least two different time points. Simulations showed that the method had no bias in the estimation of evolutionary rates and that it was robust to tree rooting and topological errors. We show that the evolutionary rates of HIV-1 subtype B and C epidemics have changed over time, with the rate of evolution inversely correlated to the rate of virus spread. For subtype B, the evolutionary rate slowed down and tracked the start of the HAART era in 1996. Subtype C in Ethiopia showed an increase in the evolutionary rate when the prevalence increase markedly slowed down in 1995. Thus, we show that the evolutionary rate of HIV-1 on the population level dynamically tracks epidemic events.

AIDS Cholangiopathy in the Era of HAART: Endangered or Extinct?

AIDS Cholangiopathy in the Era of HAART: Endangered or Extinct?

Incidence of Non-AIDS-Defining Malignancies in HIV-Infected Versus Noninfected Patients in the HAART Era: Impact of Immunosuppression

The incidence of non-AIDS-defining malignancies (non-ADMs) is reported as unchanged or increasing in the highly active antiretroviral therapy era. Whether incidence of non-ADM is significantly higher in HIV-infected than in HIV-uninfected patients remains unclear. Incidence rates of malignancies were calculated in a cohort of veterans in care for HIV-infected and age, race, and gender-matched uninfected patients from 1997 to 2004. For HIV-infected patients, CD4 counts closest to first observation date were compared between those with and without cancer. Thirty three thousand four hundred twenty HIV-infected and 66,840 HIV-uninfected patients were followed for a median of 5.1 and 6.4 years. The incidence rate ratio of HIV infected to HIV uninfected was 1.6 (1260 vs. 841 per 100,000 person-years; 95% confidence interval: 1.5 to 1.7). Incidence rate ratio for individual cancers was highest for anal cancer (14.9; confidence interval: 10.1 to 22.1). Among HIV-infected patients, median CD4 counts were lower for those with non-ADM (249 vs. 270, P = 0.02), anal cancer (156 vs. 270; P < 0.001), and Hodgkin lymphoma (217 vs. 269; P = 0.03). Prostate cancer was associated with a higher CD4 count (311 vs. 266; P < 0.001). In the highly active antiretroviral therapy era, the incidence of non-ADMs is higher among HIV-infected than HIV-uninfected patients, adjusting for age, race, and gender. Some non-ADMs do not seem to be associated with significantly lower CD4 counts.

Hyposalivation, xerostomia and oral health status of HIV-infected subjects in Thailand before HAART era

The aims of this study were to determine hyposalivation, xerostomia, and oral health status of HIV-subjects in Thailand before highly active antiretroviral therapy era. Oral examination and measurement of saliva flow rate of both unstimulated and wax-stimulated whole saliva were performed in 135 subjects (56 HIV-subjects, mean age: 34.5 years, and 79 non-HIV controls, mean age: 29.5 years). Presence of oral candidiasis, cervical root caries, and number of existing teeth were recorded. Microbiological investigation of oral Candida was conducted using oral rinse technique. Risk factors associated with hyposalivation and xerostomia were analysed. The unstimulated flow rates in HIV-subjects and non-HIV controls were 0.19 and 0.33 ml/min (P = 0.0024). For stimulated flow rates, the corresponding figures were 1.45 and 1.62 ml/min (P = 0.31). The unstimulated flow rate was significantly higher in the asymptomatic HIV-subjects: 0.17 ml/min, when compared with the symptomatic/AIDS group 0.11 ml/min (P = 0.003). No significant difference between the groups could be found with respect to stimulated flow rate. Hyposalivation was significantly associated with the colony forming unit of Candida. Smoking and alcohol consumption were significantly associated with hyposalivation, but not xerostomia. The following factors were significantly associated with both hyposalivation and xerostomia; sex, stage of HIV infection, risk group of HIV infection, systemic disease, and medication use. Salivary flow rate of HIV-subjects in Thailand was affected by HIV infection. The rate was significantly decreased with advanced stage of the disease. Various factors including medication use were associated with hyposalivation and xerostomia among the subjects.

Mortality among HIV-Infected Patients in Resource Limited Settings: A Case Controlled Analysis of Inpatients at a Community Care Center

PROBLEM STATEMENT: Despite massive national efforts to scale up Antiretroviral Therapy (ART) access in India since 2004, the AIDS death rate was 17.2 per 100,000 persons during 2003-2005. In the era of HAART in resource poor settings, it is imperative to understand and address the causes of AIDS related mortality. This collaborative study aimed at defining the predictors of mortality among people living with HIV/AIDS (PLHA) admitted during 2003-2005 to the Freedom Foundation (FF) Care and Support facility, Bangalore, India. APPROACH: Fifty consecutively selected HIV-infected patients who died during the study period and 50 HIV-infected patients matched by age, gender, route of transmission, nutrition status and stage of disease who survived at least 12 months post-ART were included in this study. The impact on mortality by factors such as: Hemoglobin, CD4+T lymphocyte counts, weight loss and Opportunistic Infections (OIs) were studied. Statistical analyses were done by Chi-square, Fisher's Exact Test, Kaplan-Meier and multivariate logistic regression. RESULTS: Recurrent diarrhea was a significant risk factor for mortality (OR = 12.25, p = 0.004), followed by a diagnosis of pulmonary tuberculosis (TB) at first admission (OR = 4.86) while TB in general also negatively impacted survival (p = 0.002). Though not statistically significant, Pneumocystis carinii pneumonia, Cryptococcal meningitis and Toxoplasmosis also negatively affected survival. Mortality was high among those not on HAART (81%) while it was significantly reduced (28%) among those on HAART (p<0.001). Patients who died had elevated liver enzymes (p = 0.027) and significant weight loss (p = 0.012). Mortality was high among patients irregular with their medical follow-up (p<0.001). CONCLUSION: Interventions that facilitate early OI diagnosis and treatment especially diarrhea and TB may reduce mortality in HIV. HAART alone without proper OI management and nutrition did not prevent mortality among PLHA. In resource poor settings, it becomes imperative to focus on low cost tools and increased capacity building along with regular clinical follow-up for diagnosis and early treatment of OIs. Further studies are warranted to explore benefits of initiating HAART earlier than currently recommended.

The Roles of Ethnicity and Antiretrovirals in HIV-Associated Polyneuropathy: A Pilot Study

In the pre-highly active antiretroviral therapy (HAART) era, distal sensory polyneuropathy (DSP) was associated with markers of advanced HIV infection and the use of neurotoxic antiretrovirals (ARVs). As HAART became widespread, and the AIDS epidemic shifted into minority populations, the risk factors for DSP became less clear. We explore the roles of ethnicity and ARV in the development of DSP in an HAART era cohort. Data from 336 HIV-positive adults were obtained from the Manhattan HIV Brain Bank. One hundred four participants had no DSP at entry visit; at least 1 follow-up visit; and a self-identified ethnicity of non-Hispanic white, Hispanic, or African American. Fifty percent of participants developed DSP; of those, 67% were symptomatic. Participants who developed DSP were older (P = 0.02) and had higher CD4 counts (P = 0.001). ARV-DSP was more common in Hispanics (P = 0.02) and intravenous drug users (P = 0.02). There was a trend for higher pain scores in Hispanics with symptomatic DSP (P = 0.08). This study suggests that there are ethnic disparities in the clinical manifestations of HIV-related neuropathies including pain and the susceptibility to ARV-DSP. Further studies of larger cohorts are indicated to explore the etiology of these differences.

Anal and cervical cytologic abnormalities among HIV-infected women in the era of HAART

Background Cervical human papillomavirus (HPV) infections and abnormal cervical cytology are more prevalent and persistent in HIV-infected compared with uninfected women. Less is known about anal HPV infections and abnormal anal cytology in women and whether findings in the cervix correlate with findings in the anus. The correlation between cytology and histology in the anal area has been even less studied. Here we evaluate the prevalence of anal and cervical cytologic abnormalities and evaluate if the abnormal cytology is associated with abnormal histology as evaluated by biopsies.

Systematic Evaluation and Description of Anal Pathology in HIV-Infected Patients During the HAART Era

This study aimed to determine the prevalence of macroscopic anal lesions and associated factors in HIV-infected outpatients during the era of highly active antiretroviral therapy. A randomly selected sample of patients with HIV-infection receiving follow-up care in the infectious diseases department of Bichat University Hospital was invited to participate in a systematic screening program consisting of anal examination with anoscopy and a standardized questionnaire. Of 516 patients, 473 (92 percent) participated. Overall, 208 patients (44 percent) had at least one anal macroscopic lesion: 108 patients (22.8 percent) had human papilloma (HPV)-related lesions (condyloma with or without dysplasia), 67 (14.2 percent) had hemorrhoidal disease, 50 (10.6 percent) had anal fissures, and 44 (9.3) percent had other anal lesions. Independent significantly associated factors for anal condyloma were history of anal condyloma (OR, 2.09) and median number of episodes of sexual intercourse per month (OR, 1.03) in men who have sex with men; history of genital condyloma (OR, 26.74), and unprotected sexual intercourse (OR, 7.47) in heterosexual men; and CD4 cell count below 200/mm3 (OR, 6.02), receptive anal intercourse (OR, 6.37), and history of anal condyloma (OR, 16.69) in women. Neither sexual behavior nor characteristics related to HIV infection were associated with hemorrhoidal disease or anal fissure. Because patients with HIV infections have a high prevalence of unreported anal lesions that may be highly contagious, involve risk of anal neoplasia, or negatively affect quality of life, systematic anal screening should be conducted in the HIV-infected population.

Longer Duration of HBV-Active Antiretroviral Therapy is Linked to Favorable Virological Outcome in HIV-HBV Co-infected Patients

Background: HBV-HIV co-infection is associated with increased liver-related morbidity and mortality. Herein we analyzed HBV-related virologic and clinical outcomes in HBV-HIV patients in the HAART era. Methods: HBsAg positive HIV-infected patients followed at a US academic center between 1990 and 2008 were assessed in a retrospective and longitudinal study. Factors associated with HBsAg and/or HBeAg clearance and with advanced liver disease were evaluated using logistic regression. Results: 72 patients were evaluated. Their median time of follow-up and of adherence to HBV-active HAART were 3 and 1 years, respectively. HBeAg and HBsAg cleared in 17.6% and 5.5% of patients, respectively. More prolonged use of HBV-active HAART predicted clearance of HBeAg (odds ratio [OR] 2.66, 95% CI 1.15–6.16, p = .02) and of HBsAg (OR 1.54, 95% CI 1.02–2.31, p = .04). Patients clearing HBsAg tended to have higher baseline CD4 (mean CD4 counts: 550 vs. 246 cells/mm3; p = .06). Rate of diagnosis of liver-related complications and death were 24.6/1,000 and 10.5/1,000 patient-years, respectively. Higher ALT levels before HAART initiation were associated with the diagnosis of cirrhosis during follow-up (OR 1.02, 95% CI 1.002–1.03, p = .02). Conclusions: Prolonged use of HBV-active HAART favors HBsAg and HBeAg clearance in HIV-HBV co-infected patients. Those with higher ALT levels at presentation have higher risk of being diagnosed with cirrhosis during the first few years of follow-up.

138 Prevalence of Human Papillomavirus (HPV) Infection among HIV-positive women in the Pre-HAART and HAART era in a Nigerian Clinic

138 Prevalence of Human Papillomavirus (HPV) Infection among HIV-positive women in the Pre-HAART and HAART era in a Nigerian Clinic

A retrospective analysis of HIV-associated Kaposi's sarcoma in patients with non-detectable HIV viral loads and CD4+ counts greater than 300 cells/μL

In the HAART era, the incidence of HIV-associated Kaposi's sarcoma (KS) has declined precipitously for countries with ready access to anti-retrovirals. Patients with newly diagnosed KS typically have low CD4+counts and high HIV viral loads (VLs). Several recently published reports (NEJM 2007;357:1352–3, NEJM 2008;358:535–6, AIDS 2008;22:551–2) suggest that patients with KS may require treatment despite effective HAART and that KS may progress even in the setting of suppressed HIV VLs and adequate CD4+ counts. To investigate this further, we examined the demographic and HIV-related clinical data of 91 KS patients attending our HIV outpatient clinic between 1996 and 2008. Twenty of the 91 patients (22%) had either newly diagnosed KS or persistent or progressive disease despite CD4+ counts >300 cells/μL and undetectable HIV VLs. Nineteen of these 20 patients were males. The median age was 43 years (range 25 to 59), the median time since onset of HIV infection was 156 months (range 24 to 276) and the median duration of HAART was 60 months (range 12 to 144). Nine (45%) patients had a KS stage of T0S0, five (25%) had T1S0, three (15%) had T0S1, three (15%) had T1S1; no patient had KS visceral involvement. All 20 patients received specific anti-KS treatment in addition to HAART including liposomal doxorubicin (65%), paclitaxel (15%), radiation (20%) and novel clinical agents (25%). After a median follow up of 52 months (range 6 to 120), eight (40%) had complete regression of KS, six (30%) had partial regression, one (5%) had stable disease and five (25%) had KS progression. In this retrospective analysis, a substantial proportion of KS patients had undetectable HIV VLs and CD4+counts greater than the level typically associated with opportunistic infections and required systemic anti-ks therapy. This raises important questions regarding the mechanisms of KS progression and the management of KS in such patients.

A role for ageing and HIV infection in HIV-related cancer risk

We read with interest the recent article by Crum-Cianflone et al.[1] describing the independent predictors of incident AIDS-defining and non-AIDS-defining cancer in their multicenter, prospective natural history study of 4498 US military beneficiaries diagnosed with HIV between 1984 and 2006. Analyses were adjusted for year of HIV diagnosis and stratified by HIV diagnosis era (<1996 and >1996). Multivariate risk factors for non-AIDS-defining cancer (n = 135; most common cancer, nonmelanoma skin cancer n = 63) included increasing age at HIV diagnosis and white race; there was no association with latest CD4 cell count or HAART use. The authors concluded that the ageing of the HIV population was the primary factor associated with the rising rates of non-AIDS-defining cancer between the pre-HAART and post-HAART eras. Cumulative duration of immunosuppression was not assessed. The finding of an absence of an association between markers of immune deficiency and non-AIDS-defining cancer risk differs with those from two recently published cohort studies. The D:A:D study examined risk factors for mortality due to AIDS-defining and non-AIDS-defining cancer in 23 437 HIV-positive patients on HAART [2]. The independent risk factors for death from a non-AIDS-defining cancer (n = 193; most common cancer, lung cancer n = 62) were current age, latest CD4 cell count, duration of exposure to HAART, hepatitis B status, and calendar year. Interestingly, cumulative duration of immunosuppression, defined as the total time spent with a CD4 cell count less than 200 cells/μl, was significant in univariate modeling but not after adjustment for latest CD4 cell count. The Chelsea and Westminster HIV cohort study examined risk factors for incident non-AIDS-defining cancer in 11 112 HIV-positive patients between 1983 and 2007 [3]. Nadir CD4 cell count less than 200 cells/μl and receipt of HAART independently predicted risk of non-AIDS-defining cancer (n = 150; most common cancer, anal cancer, n = 44) after adjustment for age, sex, ethnic group, AIDS-defining condition, and duration of HIV infection more than 5 years. In the multivariate model, HIV infection for more than 5 years was associated with a nonsignificantly increased risk [hazard ratio (HR) 1.44, 95% confidence interval (CI) 0.97–2.14]. Site-specific analyses were also performed, but the risk estimates were very imprecise. We believe that the findings from these studies suggest that HIV-related immunosuppression does play an important role in the risk of specific cancers in the HAART era. The remarkable similarity in the range of cancers occurring at excess rates in solid organ transplant recipients and people with HIV infection strongly supports an effect of long-term immunosuppression on cancer incidence [4]. Independent risk factors for immune-related cancers such as nonmelanoma skin cancer [5] and lip cancer [6] in kidney transplant recipients include a strong positive association with both increasing age and increasing duration of immunosuppression. We recommend that future, large-scale studies of cohorts in the HAART era examine the independent effects of ageing, the time-dependent severity of immunosuppression, and the cumulative duration of immunosuppression on cancer risk. Furthermore, we suggest that these analyses be performed for individual cancers or perhaps for groups of related cancers, such as those associated with infection by the same virus. Interpretation of risk factor analyses based on all ‘non-AIDS-defining cancers’ is very challenging, given the broad array of cancers included in this classification and the differential effect of immunodeficiency on cancer risk [4]. Findings from site-specific risk factor analyses will assist in the development of strategies to minimize or prevent the occurrence of cancer in patients with long-term immune deficiency. Acknowledgement C.M.V. is supported by a National Health and Medical Research Council Career Development Award (ID 510346) and a Cancer Institute NSW Career Support and Development Fellowship (ID 07-CDF-1/38). M.T.V. is supported by a National Health and Medical Research Council Postgraduate Scholarship Award (ID 401131) and a Cancer Institute NSW Research Scholar Award (06/RSA/1/28).

Infections in the HIV-infected child

The HIV pandemic has given rise to a growing population of children at risk for infectious disease, particularly in the developing world where the majority of the estimated 2.5 million children living with human immunodeficiency virus (HIV) worldwide reside. This review will explore the opportunistic infections encountered in the HIV-infected child. Due to space constraints, only the commonest acquired immunodeficiency syndrome (AIDS)-defining infections, including mycobacterial, fungal, viral and parasitic diseases, will be discussed. The epidemiological, clinical and morphological features unique to the HIV-infected child will be highlighted, with special emphasis on the altered or unusual histopathological patterns that may be encountered and ancillary tests that may be valuable in confirming the diagnosis. Where applicable, the changing trends in the era of HAART, including immune reconstitution inflammatory syndrome (IRIS), will be addressed. Ultimately, we hope to arm the practising histopathologist with information that will facilitate the accurate and timely diagnosis of imminently treatable opportunistic infections in the HIV-positive child.