HAART Era Research Articles

Outcomes of hematopoietic stem cell transplant (HSCT) in HIV patients in HAART era.

7030 Background: Prior studies have shown that outcomes of HSCT in HIV patients are similar to non-HIV patients since effective implementation of HAART by 1998; but they are limited by small sample...

Sa1464 An Endoscopic Study of Upper Digestive Tract Disorders in Patients Infected With Human Immunodeficiency Virus in the Era of HAART

Sa1464 An Endoscopic Study of Upper Digestive Tract Disorders in Patients Infected With Human Immunodeficiency Virus in the Era of HAART

Frequency and genotype of human parvovirus B19 among Iranian patients infected with HIV.

The human parvovirus B19 (B19) usually causes a subclinical infection in immunocompetent individuals. Whereas immunocompromised individuals such as patients infected with HIV are at risk of persistent anemia due to B19 infection. Only few studies have been carried out on distribution and molecular epidemiology of B19 in Iran. We aimed to determine the frequency and genotype of B19 among Iranian patients infected with HIV. We conducted a survey on 99 HIV patients and 64 healthy controls. IgG and IgM antibodies against B19 were detected by ELISA and B19 DNA was assessed by nested PCR. PCR products were subjected to direct sequencing and classified after phylogenetic analysis. The prevalence of B19 immunoglobulin was 11.1% for IgG and 1% for IgM. B19 DNA was detected in 13.1% of cases. The prevalence of B19 IgG, IgM, and DNA in control group was 25%, 1.6%, and 9.4%, respectively. B19 IgG was significantly lower in HIV group than in normal controls. There was no significant difference regarding anemia between cases and controls. All sequenced B19 isolates belonged to genotype 1A with low genetic diversity. Our findings indicated that in the HAART era, the importance of B19 infections in HIV patients may be limited whereas persistent B19 viremia in the circulation of healthy controls raises a potential concern in blood donations.

HAART slows progression to anal cancer in HIV-infected MSM.

Antiretrovirals do not prevent anal intraepithelial neoplasia. However, the influence of antiretrovirals in the natural history of invasive anal cancer is less clear. The objective is to investigate the impact of antiretrovirals in the time to the development of anal cancer in HIV-positive MSM. A retrospective analysis of cases of anal cancer in a cohort of HIV-positive MSM receiving antiretrovirals between 1988 and 2008. Time from first CD4 cell count or HIV RNA viral load test to anal cancer diagnosis was analysed using Cox regression and Kaplan-Meier curves. Anal cancer cases treated in the era prior to HAART (<1996) were compared with those treated later (1996-2008). Anal cancer cases (n = 37) were compared with a cohort of 1654 HIV-positive MSM on antiretrovirals. Antiretrovirals were started in the pre-HAART era by 70% of cancer cases, and median CD4 cell count nadir was 70 cells/μl (10-130). Time to development of anal cancer was shorter for cases treated during the pre-HAART era [adjusted hazard ratio (AHR) 3.04, 95% confidence interval (95% CI) 1.48-6.24, P = 0.002], with a CD4 cell count nadir less than 100 cells/μl (AHR 2.21, 95% CI 1.06-4.62, P = 0.035) and longer duration of CD4 cell count less than 100 cells/μl (AHR 1.33, 95% CI 1.11-1.58, P = 0.002). Results show that severe immunosuppression and starting therapy pre-HAART are associated with an increased risk of anal cancer. HIV-positive MSM initiating antiretrovirals during the HAART era (1996-2008) had a longer time to the development of anal cancer than those treated pre-HAART. Our results suggest that early use of HAART may delay progression to anal cancer.

Plasmablastic Lymphoma in the Testis and Duodenum: A Case Report and Literature Review

Plasmablastic lymphoma (PBL) is a rare and highly aggressive subtype of non-Hodgkin’s lymphoma (NHL) associated with human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV). There are over 300 reported cases of PBL, of which over 120 are reported in HIV-positive patients. Of HIV-negative patients, patients were either immunocompetent or immunosuppressed transplant recipients. Initial reports highlighted cases arising in the oral cavity of HIV patients and this remains the most prevalent site of disease. However, other sites such as the gastrointestinal tract and skin are the next most common sites. Only three cases have involved the testes, a sanctuary site. Of gastrointestinal sites, there are only a handful of cases with gastric involvement. In the pre-human antiretroviral therapy (HAART) era, median overall survival was dismal. However, prognosis has improved since their advent. There is no significant difference in the survival of HIV-positive and HIV-negative PBL patients. It should be emphasized that due to the scarcity of cases, there are no established standards of care or prospective therapeutic trials for the management and treatment of PBL. Chemotherapy remains the standard approach, though selecting a regimen is still controversial and while response has been good, overall survival remains poor. Since 1995, autologous hematopoietic cell transplantation (AHCT) has been the standard of care for relapsed chemosensitive HIV-negative NHL. In the era of HAART, this has become feasible for HIV patients. A few studies have suggested that use of AHCT in the first line setting and relapsed or refractory disease may confer better outcomes. Herein we describe a unique case of involvement in the testis and duodenum, and there are no previous reports of a patient presenting with both gastrointestinal and urogenital involvement. J Hematol. 2015;4(3):196-201 doi: http://dx.doi.org/10.14740/jh217w

HIV in Intensive Care Unit: Concerns and Constraints of Intensivists

The increasing prevalence of HIV (human immunodeficiency virus) infection in recent times has led to increasing exposure, and the possibility of nosocomial transmission of HIV. The present day scenario highlights the need for intensivists to enforce strict adherence to infection control protocol at site when working in ICU. Thus strict adherence to Standard precautions when handling body fluids especially hand washing, proper management of accidental needle-stick injury and scientific disposal of biomedical waste along with current PEP guidelines are of paramount importance. In the HAART era, though hospitalisation of HIV infected patients has significantly decreased, but the rate of ICU admissions is still high. HIV patients may be admitted to ICU for many reasons, of which acute respiratory failure as a result of opportunistic infections accounts for approximately 25-50%. Today, HIV patients are being admitted to the ICU for medical and surgical causes unrelated to their HIV infection, such as malignancies, pacemaker implant, liver and renal diseases, minimal invasive surgeries like laparoscopic ones, orthopaedic surgeries for fractures and implants, brain surgery for road traffic accident injury are only a few. The number of persons living with HIV/AIDS (PLWHA) has increased and critical care specialists may be more likely to admit more HIV patients to the ICU and pursue aggressive life-support measures. But for resource constrained countries, where population and ICU bed ratio are abysmally low, decisions for admission in ICU by critical care specialists are often made in the absence of explicit policies and guidelines. Global and national commitments are required, providing proper HIV treatment and prophylaxis without discrimination and maintaining accountability and code of ethics.

Central nervous system manifestations in human immunodeficiency virus patients in the antiretroviral therapy era - Scenario from a developing country

Background: Central nervous system (CNS) infections associated with Human immunodeficiency virus (HIV) has decreased markedly in the developed countries. However, the scenario is different in Indian patients and is not unusual to have CNS infections as their initial presentation. Considering this, we undertook this study to look at the incidence of CNS manifestations in HIV infected patients. Materials and Methods: This was a cross sectional study conducted in the Departments of Medicine and Neurology in Christian Medical College Ludhiana, a tertiary teaching institution in North West India. All the HIV infected patients with Central nervous system manifestations who presented to our institution from 1st April 2009 to 31st of March 2014 were included in the study. The demographic and clinical profile along with the outcome of these patients was studied. Results: There were 280 patients diagnosed during this 5 year period, 43(15%) of who had CNS manifestations. The male: female ratio was 5:1. Majority of them were in the age group of 31 to 50 years of age (68.89%).In 72% of patients CNS manifestations were the initial manifestation of HIV infection.The CNS manifestations noted were cryptococcal meningitis in 20, toxoplasmosis in 3, CNS tuberculosis in 11, PMLE in 6, ischemic stroke in 4 and Diffuse B cell Lymphoma (DLBCL) with aseptic meningitis in 1. Conclusions: Even though in the era of HAART the incidence of CNS manifestations has decreased, CNS manifestations continue to be the presenting symptom for HIV infection in over 16% of the cases.

Risk of non-Hodgkin lymphoma subtypes in HIV-infected people during the HAART era: a population-based study.

HIV-infected people have greatly elevated risk of non-Hodgkin lymphoma (NHL), particularly the AIDS-defining NHL subtypes: diffuse large B-cell lymphoma, Burkitt lymphoma and primary lymphomas arising in the central nervous system. The goals of this analysis were to comprehensively describe risks of NHL subtypes, especially those not well studied, among HIV/AIDS patients; examine risks specifically in the HAART era; and distinguish risks in HIV-infected individuals prior to diagnosis with AIDS. Population-based registry linkage study. We used data from the US HIV/AIDS Cancer Match Study from 1996 to 2010 (N = 273 705) to calculate standardized incidence ratios (SIRs) comparing subtype-specific NHL risks in HIV-infected people to those in the general population, and used Poisson regression to test for differences in SIRs between the HIV-only and AIDS periods. NHL risk was elevated 11-fold compared to the general population, but varied substantially by subtype. AIDS-defining NHL subtypes comprised the majority, and risks were high (SIRs ≥17), but risks were also increased for some T-cell lymphomas (SIRs = 3.6-14.2), marginal zone lymphoma (SIR = 2.4), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (SIR = 3.6), and acute lymphoblastic leukemia/lymphoma (SIR = 2.4). HIV-infected people in the HAART era continue to have elevated risk of AIDS-defining NHL subtypes, highlighting the contribution of moderate and severe immunosuppression to their cause. Whereas non-AIDS-defining subtypes are much less common, immunosuppression or other dysregulated immune states likely play a role in the cause of some T-cell lymphomas, marginal zone lymphoma, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, and acute lymphoblastic leukemia/lymphoma.

Significantly Worse Colostomy-Free Survival in Human Immunodeficiency Virus–Positive Patients After Definitive Chemoradiation for Anal Cancer

Human immunodeficiency virus (HIV) status may affect toxicity, disease control and organ preservation after definitive chemoradiation therapy (CRT) for anal cancer. However previous reports are limited by small patient numbers, the use of split course radiation therapy (RT), and patient treated in the pre-HAART era. Here, we report the largest series to date comparing toxicity, disease outcomes and organ preservation between HIV+ and HIV- patients with anal cancer treated with modern RT techniques in the HAART era. We retrospectively reviewed 110 consecutive patients, 39 HIV+, 71 HIV-, who underwent definitive CRT for anal cancer at a single institution between 2004 and 2013. Data on patient characteristics, RT dose and technique, treatment toxicity and treatment outcomes were collected from patient charts. Overall survival (OS), disease-free survival (DFS) and colostomy-free survival (CFS) were investigated. Chi-square test was used to compare frequencies and t-test was used to compare means. Kaplan-Meier survival was calculated and differences were evaluated by Log-rank statistic. Median follow-up was 15 months. HIV+ patients were younger (mean age 51 vs 65, p<.001) and predominantly male (84% vs 16%, p<.005). Five-year OS was 38% in HIV+ and 61% in HIV- (p = .076). Five-year DFS was 28% in HIV+ and 79% in HIV- (p = .074). Five-year CFS was 67% in HIV+ and 88% in HIV- (p = .03). There were no significant differences in T, N, M or stage group. Of 39 HIV+ patients, only 3 (8%) had a CD4 cell count 10 days between HIV+ and HIV- patients (33% vs 27%, p = .487), or in mean number of days beyond expected RT course (13 vs 8 days, p = .20). In this series, HIV+ patients had significantly worse CFS than HIV- patients. While there was no significant difference in OS or DFS, there was a trend towards significance. Delays in starting treatment may contribute to worse outcomes. Acute toxicity and treatment interruptions do not appear to play a role in higher risk of recurrence and salvage surgery. HIV+ patients undergoing treatment for anal cancer should be counseled appropriately regarding the higher risk of colostomy. Further studies are necessary to establish the etiology of this difference, however impaired immune response in HIV+ patients may play a role in difference in outcomes.

Prevalence and predictors of blood-brain barrier damage in the HAART era

Blood-brain barrier damage (BBBD) is prevalent in HIV-positive patients and may enhance cell trafficking to the central nervous system. A retrospective analysis in adult HIV-positive patients with no central nervous system disease was conducted in order to estimate the prevalence and risk factors of BBBD (according to cerebrospinal fluid to plasma albumin ratios). One hundred fifty-eight HIV-positive adult patients were included. BBBD impairment and intrathecal IgG synthesis were respectively observed in 45 (28.5 %) and 100 patients (63.3 %). Low CD4 nadir and high CSF HIV RNA were independently associated with both abnormalities. BBBD is common in HIV-positive patients, and its main determinants are advanced immune depression and compartmental viral replication.

Causes of prolonged fever among HIV infected patients- utility of an algorithmic approach - a single centre study from south India

Background Availability of ART for the last one decade has changed the pattern of morbidity among HIV infected patients. Researchers from Christian Medical College Vellore had developed an algorithm for evaluation of prolonged fever in the pre HAART era in India. The purpose of this study was to assess utility of this algorithm in the current HAART era to identify causes of prolonged fever and correlate with CD4 count, WHO staging and ART status.

A study on prevalence of anemia and growth pattern among HIV infected children and adolescents from rural areas attending VCTC and ART center Govt. General Hospital, Vijayawada, A.P., India

Results Totally 125 subjects of age group 1-20 years were included in the study. Among 125 HIV+ subjects only 45 subjects were in HAARTera, 75 subjects in preHAART era and 5 subjects died during the study period. The study patients in HAART era showed a significant increase (p<0.001) in CD4 counts from 174 to 902 cells/ cmm, significant decrease (p<0.001) in Hb content from 7.3 to 6.5 gm/dL and significant increase (p<0.05) in BMI level from 18.1 to 22.6 from baseline to follow up treatment after 18 months. The study patients in preHAART era showed a significant increase (p<0.05) in mean CD4 counts from 592 to 790 cells/cmm from initial count to count after 18 months. The subjects in preHAART era showed low level of Hb content 6.9 gm/dL in male and 6.3 gm/dL in female subjects; the mean BMI level was 20.43 in male and 18.47 in female subjects.

Progressive disseminated histoplasmosis in the HIV population in Europe in the HAART era. Case report and literature review

In highly endemic areas, up to 20 % of human immunodeficiency virus (HIV)-infected persons will develop progressive disseminated histoplasmosis (PDH). Europe is not endemic to histoplasmosis, and the disease is mainly found in immigrants often co-infected with HIV. We present a case of a patient with HIV and PDH highlighting the possible diagnostic difficulties that may arise in a non-endemic area and review the literature of histoplasmosis in the context of HIV infection with special focus on Europe. When cellular immunity wanes (usually at CD4 T-lymphocyte counts <150 cells/μL) histoplasma infection, acquired earlier, can reactivate and disseminate. PDH is an acquired immune deficiency syndrome(AIDS)-defining disease and a life-threatening infection, with a clinical spectrum ranging from an acute, fatal course with lung infiltrates and respiratory failure, shock, coagulopathy and multi-organ failure, to a more subacute disease with focal organ involvement, pancytopenia and hepatosplenomegaly. Mortality rates remain high for untreated patients, but early diagnosis, proper antifungal treatment and early initiation of antiretroviral therapy have improved the prognosis. European infectious diseases physicians, microbiologists and pathologists must be aware of histoplasmosis, particularly when facing HIV-infected immigrants from endemic areas. This is increasingly important due to migration and travel activities from these areas.

157 Pathogenesis of Epstein-Barr Virus-driven lymphomas of HIV+ patients

Human Immunodeficiency Virus (HIV)+ patients have an increased risk to develop lymphomas, including a significant fraction of histotypes associated with Epstein-Barr Virus (EBV) infection. Although restoration of EBV-specific T-cell function induced by HAART has led to a decreased incidence of the more immunogenic EBV-associated lymphomas, such as immunoblastic and primary central nervous system lymphomas, other EBV+ histotypes are still prevalent in the HAART era, particularly Hodgkin’s lymphoma. Therefore, factors other than HIV-induced immune suppression are probably required for the development of EBV-related lymphomas in this setting. Particular attention is being given to the identification of microenvironmental stimuli able to up-regulate critical EBV latency proteins or to induce/enhance EBV replication. In fact, recent evidence indicates that, although latency programs predominate in EBV-driven tumors, lytic EBV replication may also be of pathogenic relevance, at least in the early phases of cell transformation. This is particularly relevant for HIV-related lymphomagenesis since the underlying impairment of immune responses may favour uncontrolled activation of EBV lytic replication in latently-infected B lymphocytes. Available data indicate that local expression of distinct cytokines, including IL-4 and IL-13, may up-regulate the expression of the LMP-1 oncoprotein in B cells, thus favoring lymphomagenesis. In the search of microenvironmental factors that may promote the development of EBV-driven lymphomas in HIV+ patients, we obtained evidence supporting a pathogenic role for HIV matrix protein p17, which accumulates in lymphoid tissues of HIV+ individuals, even during HAART. Our findings support a direct contribution of HIV p17 to the development of EBV-driven lymphomagenesis and may provide the rationale for new strategies of clinical intervention in this setting.

British HIV Association guidelines for HIV‐associated malignancies 2014

<scp>B</scp>ritish <scp>HIV</scp> Association guidelines for <scp>HIV</scp>‐associated malignancies 2014

Risk Factors for Disseminated Histoplasmosis in a Cohort of HIV-Infected Patients in French Guiana

Disseminated histoplasmosis is the first AIDS-defining infection in French Guiana. A retrospective cohort study studied predictive factors of disseminated histoplasmosis in HIV-infected patients between 1996 and 2008. Cox proportional hazards models were used. The variables studied were age, sex, last CD4/CD8 count, CD4 nadir, herpes or pneumocystosis, cotrimoxazole and fluconazole use, antiretroviral treatment and the notion of recent initiation of HAART. A total of 1404 patients were followed for 6833 person-years. The variables independently associated with increased incidence of disseminated histoplasmosis were CD4 count<50 per mm3, CD4 count between 50 and 200 per mm3, a CD4 nadir <50 per mm3, CD8 count in the lowest quartile, herpes infection, and recent antiretroviral treatment initiation (less than 6 months). The variables associated with decreased incidence of histoplasmosis were antiretroviral treatment for more than 6 months, fluconazole treatment, and pneumocystosis. There were 13.5% of deaths at 1 month, 17.5% at 3 months, and 22.5% at 6 months after the date of diagnosis of histoplasmosis. The most important predictive factors for death within 6 months of diagnosis were CD4 counts and antiretroviral treatment. The present study did not study environmental/occupational factors but provides predictive factors for disseminated histoplasmosis and its outcome in HIV patients in an Amazonian environment during the HAART era.

Quality of Sleep in an HIV Population on Antiretroviral Therapy at an Urban Tertiary Centre in Lagos, Nigeria.

Aim. To determine the prevalence of sleep disturbance and its associated characteristics in HIV-positive outpatients on HAART using the PSQI. Methods. Using a cross-sectional design, 300 patients attending the outpatient HIV/AIDS clinic at the Lagos State University Teaching Hospital were recruited. Baseline data obtained included the participants' demographic data, educational qualification, and marital status. Their treatment history, including duration since HIV diagnosis, the most recent CD4 cell count, and current antiretroviral therapies, was obtained from their case records. Each participant completed the PSQI questionnaire and those with scores ≥5 were diagnosed with poor sleep quality. Results. The participants were made up of 70.7% females and 29.3% males. Their ages ranged between 18 and 74 years with a mean of 38.9 ± 10.3 years. According to the PSQI, 59.3% reported poor sleep quality. The mean score of those with poor quality sleep (9.2 ± 3.3) was comparable to that of those with good quality sleep (1.26 ± 1.4). P < 0.001. Significant differences were observed in all the individual components of the PSQI (P < 0.001). On multivariate analyses, the independent associations with sleep quality were the duration since HIV diagnosis (P = 0.29), efavirenz based regimen (P < 0.001), and lower CD4 cell count (P < 0.001). Conclusions. Sleep disturbances are quite common in the HIV population even in the era of HAART. Early recognition via routine assessment and effective treatments could prevent the resultant complications and improve quality of life.

Reason for HIV Patients Consultation to the Emergency Department in the HAART Era: Incidence and Mortality

Aim: To describe the, incidence, the changes in the etiology and the prognosis of HIV infected patients, presenting by the first time to the Emergency Department (ED), during years 2000-2010. Study Design: Retrospective collection of data. Methods: The identification of patients was carried out by consulting, retrospectively, the medical records, of the patients that flocked to ED, by any pathology, in appreciating the diagnosis and known HIV or diagnosed during their hospital admission. Patients referred from other hospitals that had previously been visited at their ED or consultations after the first visit were excluded. Epidemiological and laboratory data were analyzed as well as, the influence of these variables on a 30 days mortality test was analyzed. Poor prognosis was defined by observing mortality at 30 days. Results: A total of 445 HIV patients were included in the study. The mean age was 40.92 ± 10 years. The infectious disease was the most frequent cause of visits to the ED. Neurological affectation was the most common cause of consultation due to non-infectious diseases. The incidence of HIV patients reported to the ED had been declining in the last decade, with a maximum peak inflow in 2001 of 41.21 patients/year. The overall mortality in the study was 8%. Logistic regression analysis showed that admission to ICU (p<0.001) was independent variables predicting mortality. Conclusion. Infectious disease is the most common cause of HIV patient consultation at the ED, with a decreasing incidence, probably related to the widespread utilization increased of HAART. Our results may serve as a benchmark reference to other Spanish centers.

A STUDY ON PREVALENCE OF ANEMIA AND GROWTH PATTERN AMONG HIV-INFECTED CHILDREN FROM RURAL AREAS ATTENDING GOVT. GENERAL HOSPITAL, VIJAYAWADA, ANDHRA PRADESH, INDIA

The present communication deals with the profile of HIV infected children belonging to pre-HAART (pre-Highly Active Anti Retroviral Therapy) era and HAART era to know the status of anemia and growth pattern who attended the ART centre, Govt. General Hospital, Vijayawada, Andhra Pradesh, India. A cross-sectional record based study was carried out in 125 HIV infected children in ART centre from 2009 to 2011. Hemoglobin, height, weight, BMI, waist and hip ratio were calculated according to the standard protocols. The CD4 count was estimated using BD FACS caliber flow cytometer and results were statistically analyzed. According to the present study 125 subjects of age group 1-20 years were chosen. The subjects in pre-HAART era (75 subjects) showed low level of Hb content 6.9 gm/dL in male and 6.3 gm/dL in female subjects; the mean BMI level was 20.43 in male and 18.47 in female subjects and showed a significant increase (p<0.05) in mean CD4 counts from 592 to 790 cells/cmm from baseline count to follow up count after 18 months. The study patients in HAART era (45 subjects) significant decrease (p<0.001) in Hb content from 7.3 to 6.5 gm/dL and significant increase (p<0.05) in BMI level from 18.1 to 22.6 and showed a significant increase (p<0.001) in CD4 counts from 174 to 902 cells/cmm from baseline to follow up treatments. Our study reinforces the finding that anemia, growth pattern of HIV infection in Indian children with prognostic significance.

HIV Dementia among HIV Positive People at Debre Markos Hospital, Northwest Ethiopia

Background: HIV dementia which impairs life by causing learning, memory, behavioral and motor disabilities is still a particular problem in the HAART era. It has been prevalent particularly in the third world and specifically in sub Saharan Africa where limited access to diagnosis, treatment, care and support has been common. Hence the assessment of HIV dementia in one of the sub Saharan countries, namely Ethiopia, particularly in Debre markos referral hospital is important. Methods: A cross- sectional study design with descriptive and analytical components was employed on 423 participants with systematic random sampling technique (with proportional allocation). Data was collected by face to face interview, observation and document review using International HIV dementia scale translated into local language (Amharic version); then it was analyzed using SPSS window 20. The level of association was dealt using confidence interval and odds ratio. Result: the prevalence of HIV dementia was 24.8%. Having no education (AOR=3.11, 95% CI (1.37, 7.04)), older age of 50 years or above (AOR=4.25, 95% CI (1.05, 17.18)), having co morbid opportunistic infection (AOR=7.48, 95% CI (4.1, 13.64)) and substance use (AOR=4.64, 95% CI (2.3, 9.36)) were significantly associated with HIV dementia. Conclusion: Despite wide spread use of HAART, HIV dementia among HIV positive people is high when compared to worldwide figure. Having no education, older age of 50 years or more, being on HAART, having co morbid opportunistic infection, being in late stages of the illness and substance use were significantly associated with HIV dementia. Recommendation: starting HAART in those who developed opportunistic infection and in those 50 years or older PLHA should be considered regardless of the CD4 count.