Active Antiretroviral Therapy Era Research Articles

Impact of Immunoglobulin Therapy in Pediatric Disease: a Review of Immune Mechanisms.

Intravenous immunoglobulin (IVIG) provides replacement therapy in immunodeficiency and immunomodulatory therapy in inflammatory and autoimmune diseases. This paper describes the immune mechanisms underlying six major non-primary immunodeficiency pediatric diseases and the diverse immunomodulatory functions of IVIG therapy. In Kawasaki disease, IVIG plays a major, proven, and effective role in decreasing aneurysm formation, which represents an aberrant inflammatory response to an infectious trigger in a genetically predisposed individual. In immune thrombocytopenia, IVIG targets the underlying increased platelet destruction and decreased platelet production. Although theoretically promising, IVIG shows no clear clinical benefit in the prophylaxis and treatment of neonatal sepsis. Limitations in research design combined with the unique neonatal immunologic environment offer explanations for this finding. Inflammation from aberrant immune activation underlies the myelinotoxic effects of Guillain-Barré syndrome. HIV-1 exerts a broad range of immunologic effects and was found to decrease serious bacterial infections in the pre-highly active anti-retroviral therapy (HAART) era, although its practical relevance in the post-HAART era has waned. Clinical and experimental data support the role of immune mechanisms in the pathogenesis of childhood epilepsy. IVIG exerts anti-epileptic effects through targeting upregulated cytokine pathways and antibodies thought to contribute to epilepsy. Applications in six additional pediatric diseases including pediatric asthma, atopic dermatitis, cystic fibrosis, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS), autism, and transplantation will also be briefly reviewed. From autoimmunity to immunodeficiency, a dynamic immunologic basis underlies major pediatric diseases and highlights the broad potential of IVIG therapy.

Opportunistic infections among individuals with HIV-1/AIDS in the highly active antiretroviral therapy era at a Quaternary Level Care Teaching Hospital.

In this study, clinical-laboratory and epidemiological characteristics are described for a group of 700 individuals with HIV (human immunodeficiency virus)/AIDS (acquired immunodeficiency syndrome) in the ART (antiretroviral therapy) era at a teaching hospital that provides a quaternary level of care, with an emphasis on opportunistic infections (OIs), co-infections and immune profile. A retrospective cross-sectional study of AIDS cases was conducted from 1998 to 2008 by reviewing medical records from the Base Hospital/FUNFARME (Fundação Faculdade Regional de Medicina), São José do Rio Preto, São Paulo, Brazil. The individuals were 14 to 75 years of age, and 458 were males. Heterosexuals accounted for 31.1% of all patients. Eighty-three percent were on ART, and 33.8% of those presented difficulties with treatment adherence. OIs were analyzed from medical records, and Pneumocystis jiroveci pneumonia was the most prevalent, regardless of the LTCD4+ (TCD4+ Lymphocytes) levels. Individuals whose viral loads were ≥10,000 showed a 90% greater chance of neurotoxoplasmosis. For P. jiroveci pneumonia, neurotoxoplasmosis, esophageal candidiasis, pulmonary tuberculosis and neurocryptococcosis, the chances of infection were higher among patients with LTCD4+ levels below 200 cells/mm3. HIV/hepatitis C virus (HCV) and HIV/hepatitis B virus (HBV) co-infections were significantly associated with death. OIs remain frequent in the ART era even in populations where the access to medical care is considered satisfactory.

Patient–provider interaction, patient satisfaction, and health outcomes: testing explanatory models for people living with HIV/AIDS

In the era of highly active antiretroviral therapy era, medication adherence and health-related quality of life (HRQOL) have become critical issues for people living with HIV/AIDS (PLWH). The purpose of this study was to test explanatory models of how patient–provider interaction and patient satisfaction are related to medication adherence and HRQOL for PLWH. A total of 344 PLWH receiving health-care services from a federally funded clinic in the southwest USA completed a survey questionnaire about their perception of interactions with providers, their satisfaction with services, their medication adherence, and their HRQOL. Comparing four latent variable structural equation models of direct and mediated effects of patient–provider interaction and patient satisfaction, the findings illustrate that the best model is one in which patient–provider interaction has a direct and positive effect on patient satisfaction, medication adherence, and HRQOL. These findings suggest that quality patient–provider interaction is a critical element of health-care services for PLWH, while patient satisfaction is an outcome measure and not a mediating factor for medication adherence and HRQOL.

Immune Activation: Contribution to AIDS-Associated Non-Hodgkin Lymphoma.

HIV infection is associated with a greatly elevated risk for the development of non-Hodgkin lymphoma (NHL), which while diminished, remains elevated in the highly active antiretroviral therapy (HAART) era. Chronic B cell activation, driven by contact with HIV virions, B cell-stimulatory cytokines, viruses (EBV, HPV, HCV), and by high levels of antigenic stimulation occurs in HIV infected persons, and it is seen at even higher levels in those who go on to develop AIDS-NHL. Evidence from multiple studies indicates that elevated serum levels of several B cell-stimulatory cytokines and biomarkers are seen preceding AIDS-NHL, as well as in immunocompetent persons that develop NHL. Phenotypic changes in circulating B cells also are seen preceding AIDS-NHL, including the expression of AICDA, and of cell-surface molecules and miRNA that are associated with activated B cells. HAART only partially normalizes the immune system of treated HIV+ persons as they still show clear evidence for ongoing inflammation and immune activation in, even those who show complete suppression of HIV viremia. Together, this provides ample evidence to support the notion that chronic activation of B cells contributes to the genesis of B cell lymphomas.

Initial Experience with Thrombopoetin Receptor Agonists (TRA) in 5 Patients with Refractory HIV-Associated Immune Thrombocytopenic Purpura (ITP)

Introduction: In the pre-highly active anti-retroviral therapy (HAART) era, ITP was a relatively common hematologic abnormality, which was seen in as many as 30% of patients infected with HIV. With the advent of HAART, the incidence of HIV-associated ITP has been reduced substantially, with some epidemiological studies showing contemporary rates as low as 1 to 3% (Vannappagari, Platelets 2011). In cases where HAART does not lead to adequate improvement in platelet counts, next lines of therapy have traditionally consisted of corticosteroids, including dexamethasone and prednisone, intravenous immunoglobulin (IVIG), anti-Rho(D) immune globulin, rituximab and, in the current era, more sparingly, splenectomy. When platelet counts remain persistently <20 x 109/L despite medical and surgical interventions, patients with ITP retain a heightened risk of bleeding complications (Frederiksen, Br J Haematol 2014). The TRAs eltrombopag (Promacta®) and romiplostim (Nplate®) are effective in 59% to 88% of ITP cases in patient without HIV, and loss of response while on continued therapy is uncommon. The agents’ use in treatment of refractory HIV-associated ITP has not, however, been sufficiently studied or reported.Methods: Herein we perform a retrospective chart review of 5 patients with HIV-related ITP treated from 2009-2014. All 5 patients with HIV-associated ITP had failed at least two lines of ITP therapy before they received a TRA (table). Mean age was 34 years (18-47), 3 males and 2 females. 4 patients had CD4+ counts >200 cells/ µL, viral loads < 40 copies/mL, and platelet counts ≤20 x 109/L before starting TRA therapy.Results: Each patient responded to TRA use with a mean pre-treatment platelet count of 15 x 109/L, and this increased to a mean of 110 x 109/L 6 weeks following treatment initiation. 2 of the patients have maintained a sustained response with adequate platelet counts 3 years after discontinuing TRA therapy. 1 patient succumbed to a myocardial infarction while on eltrombopag and 1 patient, while on romiplostim, expired from complications of a presumed pulmonary embolus after undergoing lumbar spine surgery.Abstract 5014. Table:Characteristics of HIV-related ITP patients given TRACaseNadir CD4+ count (cells/µL) /HIV viral load (copies/mL)HAART RegimenCD4+ count (cells/µL) /HIV viral load (copies/mL) at time of use of TPAPlatelet count pre-TRA treatmentLines of ITP treatment before TRATRA (dose where response was observed and sustained)6 month f/u platelet countSustained Response after stopping TRA (duration)Case 1261/ 5,000Atripla®340 / <4020 x 109/L1. Pred + IVIG 2.Rituximab + DexRomiplostim (4µg/kg)158 x 109 /LYes (3 years)Case 2a284/ 74,743Atripla®300/ <402 x 109/L1. Pred 2. Pulse Dex 3.Rituximab + Dex 4. IVIGRomiplostim, then Eltrombopag (50mg)N/AN/ACase 3261/ 5,000Atripla®>300 / <4013 x 109/L1. Pred + IVIG 2.Rituximab + DexRomiplostim (2µg/kg)128 x 109 /LYes (3 years)Case 4100/ 100,000Zidovudine + Epivir + Nevirapine180 / <4039 x 109/L1. IVIG 2. Pred 3. RituximabRomiplostim (3µg/kg)52 x 109 /LbN/ACase 5100/ 2,400Truvada + darunavir + detravirine + raltegravir + ritonavir>200 / 54,00013 x 109/L1. Anti-Rho(D) 2. IVIG 3. Rituximab 4. Pulse Dex 5. Pred 6.Rituximab + Dex Eltrombopag (50mg)48 x 109 /LcNoaPatient expired prior to 6 month f/u due to myocardial infarction bPatient sustained response for 2 weeks after discontinuation of TRA cPatient to be reinitiated on maintenance therapy due to lack of compliance Abbreviations: efavirenz, tenofovir, and disoproxil fumarate (Atripla®); prednisone (Pred) dexamethasone (Dex); follow-up clinic visit (f/u)Discussion: Due to insufficient evidence, a definitive association between TRA use and the two patients who suffered thrombotic events remains speculative. Nonetheless, these events emphasize the importance of using these TRAs cautiously during periods of heightened risk of thrombosis such as post-surgery and during periods of immobility, or in patients with risk factors for thrombotic complications. While HIV-associated ITP remains an important clinical problem in the era of widespread HAART use, the availability of both romiplostim and eltrombopag give medical providers additional options in treating this disease. Further experience is needed, however, to better determine the effectiveness and, most importantly, the safety of these drugs in the context of HIV-associated ITP. DisclosuresNo relevant conflicts of interest to declare.

VIH et Cancer: état Des Connaissances

HIV infection is related to an increased risk of cancer compared with general population, both AIDS-defining cancers (Kaposi's sarcoma, non Hodgkin's lymphoma, invasive cervical cancer) and non-AIDS-defining cancers. Although the advent of the highly active antiretroviral therapy era has decreased the Kaposi's sarcoma and non-Hodgkin's lymphoma incidences, non-AIDS-defining malignancies, such as lung cancer, hepatocarcinoma, anal cancer and skin cancers, remain a major cause of morbidity and death in the HIV-infected population. The clinical presentation is often different between the infected and non-infected populations, often with a more advanced stage at diagnosis, a more aggressive pathology, and associated morbidities like immunosuppression, leading to poorer outcomes. Numerous studies have focused on HIV-related malignancies’ treatment, however specific guidelines are still missing. Practitioners have to be careful with interactions between antiretroviral and antineoplastic drugs, particularly through the cytochrome P 450. Because of this, a national multidisciplinary approach, “Cancer and HIV, ” was started in 2013 thanks to the National Institute of Cancer (INCa). The aim of this review is to present a scientific update about AIDS-and non-AIDS-defining malignancies, both in their clinical aspects and regarding their specific therapeutic management.

Lowering the limit: reducing the CD4 T-cell threshold for ophthalmic screening in patients with HIV in an ethnically diverse UK population.

BackgroundBefore highly active antiretroviral therapy, cytomegalovirus (CMV) retinitis was a major threat to vision in individuals with HIV. We investigate whether ophthalmic screening of asymptomatic HIV patients still has value in the highly active antiretroviral therapy era and consider CD4 thresholds in line with the world literature and UK experience.MethodsA retrospective chart review was conducted of all patients seen by the HIV Ophthalmic Service of a UK university hospital both before (2007–2008) and after (2011–2012) introduction of a threshold of CD4 lower than 100 cells/mm3. Data collected included CMV and HIV RNA load, CD4 cell counts and CD4 percentage, CMV-immunoglobulin G status, ocular symptoms, and evidence of HIV-related ocular disease.ResultsIn total, 54 patients were referred to the HIV ophthalmic service. Three patients failed to attend, resulting in complete data for 51 patients (n=24 for 2007–2008; n=27 for 2011–2012). Seven patients had ophthalmic manifestations of their HIV; these cases had lower CD4 counts than those with normal examinations (median [interquartile range], 9 [7–80] versus 175 [44–394]; P=0.0039; Mann–Whitney test). Six cases had HIV retinopathy without sight loss; one case had sight-threatening CMV retinitis associated with a CD4 count of 6 cells/mm3.ConclusionBefore 2008, our practice was to screen all asymptomatic patients with CD4 counts lower than 200 cells/mm3. Screening asymptomatic patients with CD4 counts below 100 cells/mm3 was not associated with any missed or late-presenting cases of CMV retinitis in our HIV population.

Acquired rifampicin resistance in thrice-weekly antituberculosis therapy: impact of HIV and antiretroviral therapy.

Risk factors for acquired rifampicin resistance (ARR) in human immunodeficiency virus (HIV)/tuberculosis coinfection, in the highly active antiretroviral therapy (HAART) era, needs evaluation. We studied the impact of HIV and HAART on ARR among patients taking thrice-weekly antituberculosis therapy. This cross-protocol analysis included patients with newly diagnosed, rifampicin-susceptible pulmonary tuberculosis, with and without HIV, enrolled in clinical trials (who took >80% of medication) at the National Institute for Research in Tuberculosis between 1999 and 2013. All patients received rifampicin and isoniazid for 6 months reinforced with pyrazinamide and ethambutol in the first 2 months, given thrice-weekly throughout the study along with HAART in one of the groups. Outcomes were categorized and multivariate logistic regression analysis performed to identify risk factors for ARR. The per-protocol results included patients with tuberculosis: 246 HIV-uninfected patients (HIV(-)TB(+)), 212 HIV patients not on HAART (non-HAART), and 116 HIV-infected patients on HAART. Median CD4 counts of the latter 2 groups were 150 and 93 cells/µL, respectively, and the median viral loads were 147 000 and 266 000 copies/mL, respectively. Compared with HIV(-)TB(+), the relative risks (RRs) for an unfavorable response in the coinfected, non-HAART and HAART groups were 2.1 (95% confidence interval [CI], 1.7-14.8; P<.0001) and 2.1 (95% CI, .9-5.2; P=.3), whereas for ARR, the RRs were 21.1 (95% CI, 2.6-184; P<.001) and 8.2 (95% CI, .6-104; P=.07), respectively. HIV-infected patients with tuberculosis treated with a thrice-weekly antituberculosis regimen are at a higher risk of ARR, compared with HIV-uninfected patients, in the presence of baseline isoniazid resistance. HAART reduces but does not eliminate the risk of ARR.

Prevalence of oral candidiasis in HIV/AIDS children in highly active antiretroviral therapy era. A literature analysis.

SummaryHighly active antiretroviral therapy has decreased the morbidity and mortality related to HIV infection, including oral opportunistic infections. This paper offers an analysis of the scientific literature on the epidemiological aspects of oral candidiasis in HIV-positive children in the combination antiretroviral therapy era. An electronic databases search was made covering the highly active antiretroviral therapy era (1998 onwards). The terms used were oral lesions, oral candidiasis and their combination with highly active antiretroviral therapy and HIV/AIDS children. The following data were collected from each paper: year and country in which the investigation was conducted, antiretroviral treatment, oral candidiasis prevalence and diagnostic parameters (clinical or microbiological). Prevalence of oral candidiasis varied from 2.9% in American HIV-positive children undergoing highly active antiretroviral therapy to 88% in Chilean HIV-positive children without antiretroviral therapy. With respect to geographical location and antiretroviral treatment, higher oral candidiasis prevalence in HIV-positive children on combination antiretroviral therapy/antiretroviral therapy was reported in African children (79.1%) followed by 45.9% reported in Hindu children. In HIV-positive Chilean children on no antiretroviral therapy, high oral candidiasis prevalence was reported (88%) followed by Nigerian children (80%). Oral candidiasis is still frequent in HIV-positive children in the highly active antiretroviral therapy era irrespective of geographical location, race and use of antiretroviral therapy.

Factors Associated With Hospitalizations Among HIV-Infected Adults in the United States: Review of the Literature.

Although improving health outcomes in human immunodeficiency virus (HIV)-infected persons has been identified as a national priority, little is known about the factors associated with hospitalizations of HIV-infected persons in the highly active antiretroviral therapy (HAART) era. Since the introduction of HAART in 1996, there has been a dramatic increase in the life expectancy of HIV-infected persons. However, aging and the long term use of HIV medications have led to an increased incidence of chronic, non-HIV-related illnesses. To improve patient outcomes, the factors that contribute to co-morbidities in HIV-infected persons need to be identified. As a first step, we will summarize the current literature on causes and contributing factors of hospitalizations in adults infected with HIV in the HAART era.

Incidence of congenital toxoplasmosis among infants born to HIV-coinfected mothers: case series and literature review

IntroductionThere is a paucity of data on the occurrence of congenital toxoplasmosis in children born to mothers dually infected with HIV and Toxoplasma gondii. ObjectiveTo evaluate aspects of the mother–infant pairs associated with vertical transmission of toxoplasmosis in women co-infected with HIV in a referral center for perinatally acquired infections in Belo Horizonte, Brazil. MethodsDescriptive study of HIV vertically exposed children, with congenital toxoplasmosis, followed at a referral center (cohort/Belo Horizonte). Prenatal and post-natal variables for the mother–infant pairs were evaluated. A literature review with no filtering for time and language was performed to identify reports of congenital toxoplasmosis in HIV vertically exposed children. ResultsAmong 2007 HIV vertically exposed children evaluated in the period from 1998 to 2011, 10 cases of congenital toxoplasmosis were identified (incidence: 0.5%, 95% confidence interval: 0.24–0.91). In searching the literature 22 additional cases in 17 reports were found. Combining the findings of our cohort with other reported cases, 50% (16/32) of congenital toxoplasmosis in HIV vertically exposed children were from Brazil. The cases of congenital toxoplasmosis in HIV vertically exposed children identified in Brazil occurred mainly in the post-Highly Active Antiretroviral Therapy era (p=0.002) and presented a lower death rate (p=0.003) than those from other countries. In the cohort/Belo Horizonte, HIV infection was identified mainly during gestation; T. gondii vertical transmission was observed in pregnant women with CD4+>500cells/mm3 and latent toxoplasmosis. High rates of ocular lesions (87.5%) and central nervous system involvement (70%) were detected. ConclusionsThe risk of vertical transmission of T. gondii in HIV-infected women is low and has been usually associated with maternal immunosuppression and elevated viral load. However, our findings of congenital toxoplasmosis in children born to HIV-infected mothers with latent toxoplasmosis and not immunosuppressed emphasize the need for careful follow-up in these cases.

Determinants of HIV Outpatient Service Utilization: A Systematic Review

Demands on HIV services are increasing as a consequence of the increased life-expectancy of HIV patients in the highly active antiretroviral therapy era. Understanding the factors that influence utilization of ambulatory HIV services is useful for planning service provision. This study reviewed factors associated with utilization of hospital based HIV out-patient services. Studies reporting person-based utilization rates of HIV-specific outpatient services broken down by patient or healthcare characteristics were eligible for inclusion. The Andersen Behavioral Model was used to organize the information extracted into pre-disposing, enabling and need components. Ten studies were included in the final review. Older age, private insurance, urban residence, lower CD4 counts, a diagnosis of AIDS, or anti-retroviral treatment were associated with higher utilization rates. The results of this review are consistent with existing knowledge regarding HIV patients' use of health services. Little information was identified on the influence of health service characteristics on utilization of out-patient services.

HIV outcomes in Hepatitis B virus coinfected individuals on HAART.

Understanding the impact of hepatitis B virus (HBV) coinfection on HIV outcomes in the highly active antiretroviral therapy (HAART) era continues to be a critical priority given the high prevalence of coinfection and the potential for impaired immunologic, virologic, and clinical recovery. Participants from the US Military HIV Natural History Study with an HIV diagnosis on HAART and serologically confirmed HBV infection status at HAART initiation (HI) were classified into 4 HBV infection (HB) groups. HIV virologic, immunologic, and clinical outcomes were evaluated by HB status. Of 2536 HIV-positive HAART recipients, with HBV testing results available to determine HB status in the HI window, HB status at HI was classified as HB negative (n = 1505; 66%), resolved HB (n = 518; 23%), isolated hepatitis B core antigen (n = 139; 6%), or chronic HB (n = 131; 6%). HIV virologic suppression and failure at 6 months or 1 year were not significantly different by HB status. A significantly faster rate of increase in CD4 cell count during the period between 4 and 12 years was observed for chronic HB relative to HB negative. Chronic and resolved HB were associated with an increased risk of AIDS/death compared with HB-negative individuals (chronic HB-hazard ratio = 1.68, 95% confidence interval: 1.05 to 2.68; resolved HB-hazard ratio = 1.61, 95% confidence interval: 1.15 to 2.25). HB status did not have a significant impact on HIV virologic outcomes, however, CD4 cell count reconstitution after HI and the risk of an AIDS event or death after HI may be associated with HB status.

The second generation of HIV-1 vertically exposed infants: a case series from the Italian Register for paediatric HIV infection.

BackgroundIn the Highly Active Antiretroviral Therapy (HAART) era, the prognosis of children perinatally infected with HIV-1 has significantly improved, so the number of perinatally-infected females entering child-bearing age and experiencing motherhood is increasing.MethodsA description of the medical history and pregnancy outcomes of women with perinatal acquired HIV-1 infection enrolled in the Italian Register for HIV infection in Children.ResultsTwenty-three women had 29 pregnancies. They had started an antiretroviral therapy at a median of 7.7 years (interquartile range, IQR 2.3 - 11.4), and had experienced a median of 4 therapeutic regimens (IQR 2–6). Twenty women (87%) had taken zidovudine (AZT) before pregnancy, in 14 cases as a starting monotherapy. In 21 pregnancies a protease inhibitor-based regimen was used. At delivery, the median of CD4+ T lymphocytes was 450/μL (IQR 275–522), and no viral load was detectable in 15 cases (reported in 21 pregnancies). Twenty-eight children were delivered through caesarean section (median gestational age: 38 weeks, IQR 36–38, median birth weight: 2550 grams, IQR 2270 – 3000). Intravenous AZT was administered during delivery in 26 cases. All children received oral AZT (median: 42 days, IQR 31 – 42), with no adverse events reported. No child acquired HIV-1 infection.ConclusionsDespite a long history of maternal infection, multiple antiretroviral regimens and, perhaps, the development of drug-resistant viruses, the risk of mother-to-child transmission does not seem to have increased among the second-generation of HIV-1 exposed infants.

Cancer Incidence in a Nationwide HIV/AIDS Patient Cohort in Taiwan in 1998–2009

The aims of this study were to investigate the cancer incidence and risk in HIV/AIDS patients relative to the general population in Taiwan. Using Taiwan's National Health Insurance Research Database, 15,269 HIV/AIDS patients were identified between 1998 and 2009. Gender-specific incidence densities (IDs) of both AIDS-defining cancers (ADC) and non-AIDS-defining cancers (NADC) after HIV infection were calculated. Age-, sex-, and period-adjusted standardized incidence rates (SIRs) were obtained using 1.8 million people from the general population as controls. A total of 1117 male and 165 female HIV/AIDS patients were diagnosed with cancer. Non-Hodgkin lymphoma (n = 196; ID = 328.79/100,000 person-years) and cervical cancer (n = 50; ID = 712.08/100,000 person-years) were the most common ADCs, whereas liver cancer (n = 125; ID = 184.52/100,000 person-years) and colon cancer (n = 11; ID = 156.66/100,000 person-years) were the most common NADCs in males and females, respectively. Period-adjusted gender-specific ADC and NADC rates decreased from more than 1500 cases/100,000 person-years to less than 500 cases/100,000 person-years (P < 0.001 for trend). SIRs of ADCs and NADCs also decreased. However, relative to the general population, increased SIRs were still seen for most cancers, many of which had an infectious etiology. The highest SIRs in ADCs and NADCs were seen in Kaposi sarcoma [SIR = 298.0, 95% confidence interval (CI): 258.16 to 343.85] and anal cancer (SIR = 19.10, 95% CI: 12.80 to 27.50). This study showed that although the cancer incidence rates have significantly decreased in the highly active antiretroviral therapy era, HIV/AIDS patients were still at increased risk of ADCs and most NADCs. Cancer screening, especially for infection-related NADCs, should therefore be promoted.

Long-term Effects of Chemoradiotherapy for Anal Cancer in Patients With HIV Infection

Despite the increasing evidence for chemoradiotherapy as standard treatment for anal cancer in patients with HIV infection, there is still some uncertainty regarding increased toxicity and adverse effects on the immune status. We report the clinical outcome of 5-fluorouracil/mitomycin C-based concurrent chemoradiotherapy for anal carcinoma in patients with HIV infection with an emphasis on the long-term course of CD4 counts and the HIV-related morbidity during follow-up. A retrospective single-institution chart review was performed. Between 1997 and 2012, 36 HIV-positive patients were treated with standard chemoradiotherapy (median tumor dose, 54 (range, 50.4-60.4) Gy at 1.8 Gy/fraction; 5-fluorouracil, 800-1000 mg/m(2), days 1-4 or 1-5; mitomycin C, 10 mg/m(2), day 1, in the first and fifth week). A retrospective analysis was performed with respect to tumor response, local control, cancer and overall survival, and toxicity. Immunological parameters, including pre- and posttreatment CD4 counts, viral load, and HIV-specific morbidity were recorded during follow-up. Chemoradiotherapy could be completed in all patients. Acute grade 3 toxicities occurred in 17/36 patients (47%). Complete response was achieved in 31 patients (86%). Five-year local control, colostomy-free, cancer-specific, and overall survival were 72%, 87%, 77%, and 74%. The median pretreatment CD4 count significantly decreased from 367 cells/μL to 139 cells/μL, 3 to 7 weeks after completion of chemoradiotherapy (p < 0.001). Four patients (11%) experienced opportunistic illnesses during the follow-up (median, 66; range, 10-164 months). This study is limited by its retrospective design and its small sample size. Our data confirm again that, in the highly active antiretroviral therapy era, anal cancer can be treated in HIV-positive patients with standard chemoradiotherapy, with a clinical outcome similar to their HIV-negative counterparts. The chemoradiotherapy-related decline of the CD4 counts, which remain decreased up to 6 years after chemoradiotherapy, was not associated with increased HIV-related clinical morbidity.

Risk factors for invasive pneumococcal disease in HIV-infected adults in France in the highly active antiretroviral therapy era

Invasive pneumococcal diseases remain frequent and severe in HIV-infected subjects. To identify opportunities for prevention, we assessed risk factors of invasive pneumococcal diseases (IPD) in HIV-infected patients over a 10-year period in France. We performed a retrospective case-control study in a reference centre of HIV management in Paris. All HIV-infected patients having suffered from IPD between 2000 and 2011 were included. Control subjects were HIV-infected with no history of IPD or pneumonia, matched by date of diagnosis of HIV with controls. Two controls were randomly selected for each subject. In all, 42 HIV-infected patients presented 44 IPD episodes during the study period and were compared to 84 controls. In the multivariate analysis, patients with IPD were more likely than controls to have a Charlson Comorbidity Index ≥2 (adjusted OR = 7.07, 95% CI 1.99-25.1, p = 0.003), CD4-cell count <200/cells/µL (aOR = 6.93, 95% CI 1.80-26.7, p = 0.005), HIV-RNA viral load >400 copies/mL (aOR = 5.56, 95% CI 1.58-19.5, p = 0.007) and a non-European origin (aOR = 4.26, 95% CI 1.02-17.9, p = 0.047). HIV-infected patients with a higher burden of comorbidities, uncontrolled HIV replication, low CD4-cell counts and/or of non-European origin are at higher risk of developing IPD. Better screening for and management of HIV infection is necessary to reduce the risk of IPD.

Clinical characteristics and outcomes in 303 HIV-infected patients with invasive fungal infections: data from the Prospective Antifungal Therapy Alliance registry, a multicenter, observational study

This analysis aimed to characterize the epidemiology, diagnosis, treatment, and outcomes of invasive fungal infections (IFIs) in patients with human immunodeficiency virus (HIV). Data were examined for HIV patients enrolled in the Prospective Antifungal Therapy (PATH) Alliance registry, a multicenter, observational study of patients with IFIs in North America from 2004 to 2008. Patient demographics, clinical characteristics, comorbidities, antifungal therapies, and survival were assessed. In total, 320 fungal isolates were identified from 303 HIV patients with IFIs in the PATH Alliance® registry. These included Cryptococcus (50.0%), Candida (33.1%), Histoplasma (9.1%), and Aspergillus (4.4%). Candida infection occurred mainly as candidemia (86.0%); Cryptococcus as central nervous system infection (76.7%); Histoplasma as disseminated infection (74.1%); and Aspergillus as pulmonary infection (81.8%). The CD4 cell count was ≤200 cells/μL in 91.2% of patients with available data. The majority of patients with Cryptococcus (77.9%), Histoplasma (100.0%), and Aspergillus (71.4%) infections had CD4 cell counts <50 cells/μL compared with 48.9% of patients with Candida infections. Patients with candidiasis were more likely to have other conditions requiring medical services compared with patients with other IFIs. Survival probability was lower in patients with Aspergillus (0.58) and Candida (0.59) infection than in patients with Histoplasma (0.84) and Cryptococcus (0.81) infection. In the highly active antiretroviral therapy era, traditional opportunistic IFIs such as cryptococcosis and histoplasmosis still mainly occur in HIV patients with CD4 counts <50 cells/μL. Fungal infections remain a clinical challenge in HIV patients with severe immunosuppression. Our data also suggest that HIV patients with CD4 cell counts >200 cells/μL and other underlying conditions may be susceptible to invasive candidiasis.

Birth Prevalence of Congenital Cytomegalovirus Among Infants of HIV-Infected Women on Prenatal Antiretroviral Prophylaxis in South Africa

A high rate of congenital cytomegalovirus (CMV) has been documented in human immunodeficiency virus (HIV)-exposed infants in industrialized settings, both in the pre- and post-highly active antiretroviral therapy (HAART) era. Only limited data on the birth prevalence of congenital CMV among infants of HIV-infected women on prenatal antiretroviral (ARV) prophylaxis are available from sub-Saharan Africa, despite a high prevalence of both infections. We evaluated the prevalence of congenital CMV in HIV-exposed infants in the Western Cape, South Africa. HIV-infected mothers were recruited in the immediate postnatal period at a referral maternity hospital between April and October 2012. Maternal and infant clinical data and newborn saliva swabs were collected. Saliva swabs were assayed by real-time polymerase chain reaction for CMV. Data were analyzed using univariate and multivariate logistic regression analyses to determine specific demographic, maternal, and newborn characteristics associated with congenital CMV. CMV was detected in 22 of 748 newborn saliva swabs (2.9%; 95% confidence interval [CI], 1.9%-4.4%). Overall, 96% of mothers used prenatal ARV prophylaxis (prenatal zidovudine, 43.9%; HAART, 52.1%). Maternal age, gestational age, prematurity (<37 weeks' gestation), type of ARV prophylaxis, length of ARV prophylaxis, birth weight, small for gestational age, and infant feeding choice were not significantly different between CMV-infected and -uninfected infants. Maternal CD4 count <200 cells/μL during pregnancy was independently associated with congenital CMV (adjusted odds ratio, 2.9; 95% CI, 1.2-7.3). A negative correlation between CMV load in saliva and maternal CD4 count was observed (r = -0.495, n = 22, P = .019). The birth prevalence of congenital CMV was high despite prenatal ARV prophylaxis, and was associated with advanced maternal immunosuppression.

Sex Differences in HIV Outcomes in the Highly Active Antiretroviral Therapy Era: A Systematic Review

To assess sex disparities in AIDS clinical and laboratory outcomes in the highly active antiretroviral therapy (HAART) era we conducted a systematic review of the published literature on mortality, disease progression, and laboratory outcomes among persons living with HIV and starting HAART. We performed systematic PubMed and targeted bibliographic searches of observational studies published between January, 1998, and November, 2013, that included persons starting HAART and reported analyses of mortality, progression to AIDS, or virologic or immunologic treatment outcomes by sex. Risk ratios (relative risks, odd ratios, and hazard ratios) and 95% confidence intervals were obtained. Sixty-five articles were included in this review. Thirty-nine studies were from North America and Europe and 26 were from Latin America, Asia, and Africa. Forty-four studies (68%) showed no statistically significant difference in risk of mortality, progression to AIDS, or virologic or immunologic treatment outcomes by sex. Decreased risk of death among females compared to males was observed in 24 of the 25 articles that included mortality analyses [pooled risk ratio 0.72 (95% confidence interval=0.69-0.75)], and decreased risk of death or AIDS was observed in 9 of the 13 articles that examined the composite outcome [pooled risk ratio=0.91 (0.84-0.98)]. There was no significant effect of sex on the risk of progression to AIDS [pooled risk ratio=1.15 (0.99-1.31)]. In this systematic review, females starting HAART appeared to have improved survival compared to males. However, this benefit was not associated with decreased progression to either AIDS or to differences in virologic or immunologic treatment outcomes.