HIV-related Immunosuppression Research Articles

Cutaneous Markers of HIV Infection and Progression

Skin and mucosal diseases can be the first manifestation of asymptomatic HIV infection, may indicate advancing immunodeficiency, or may represent systemic opportunistic infections or neoplasms. Mucocutaneous diseases are highly prevalent in the HIV-infected population and multiple pathologies are common particularly with advanced immunosuppression. The dominant HIV-associated skin diseases are infectious and inflammatory and they can cause significant morbidity. Although skin cancers are less common their prognosis is often worse. Clinical presentations are often atypical and may vary depending on the level of immunosuppression. Managing skin disease in the context of advanced immunosuppression is challenging and they often respond poorly to conventional therapies. This improves with the commencement of antiretrovirals (ARVs) and immune restoration. Despite the significant decline in HIV-related skin diseases with ARVs, the drugs themselves have brought with them a range of other skin-associated problems: adverse effects, an increased risk of drug reactions, and immune reconstitution-associated skin diseases. Therefore, the burden of skin disease remains high even in the era ARVs and the aim of this review is to equip physicians managing HIV-infected patients with knowledge of the spectrum of skin disorders associated with HIV-related immunosuppression.

Association Between Human Immunodeficiency Virus Infection and Stiffness of the Common Carotid Artery

Individuals with human immunodeficiency virus (HIV) who use highly active antiretroviral therapy (HAART) may have an increased risk for cardiovascular-related events, although the underlying mechanism remains unclear. We tested the hypothesis that carotid arterial stiffness was higher among persons using HAART compared to HAART-naïve and HIV-uninfected persons. Between 2004 and 2006, we performed high-resolution B-mode ultrasound on 2789 HIV-infected and HIV-uninfected participants of the Women's Interagency HIV Study (1865 women) and the Multicenter AIDS Cohort Study (924 men) and determined carotid arterial distensibility, which is a direct measure of carotid arterial stiffness. We used generalized estimating equations to evaluate the association between distensibility and HIV infection, CD4(+) cell count, and exposure to HAART adjusted for demographic, behavioral, and clinical characteristics. In multivariable analysis, distensibility was 4.3% lower (95% confidence interval, -7.4% to -1.1%) among HIV-infected vs uninfected participants. Among HIV-infected participants with <200 CD4(+) cells, distensibility was 10.5% lower (95% confidence interval, -14.5% to -6.2%) than that among HIV-uninfected participants, and this effect did not differ significantly by cohort or race. Concurrent HAART use was independently associated with lower distensibility among Multicenter AIDS Cohort Study participants but not among Women's Interagency HIV Study participants. Our finding that advanced HIV-related immunosuppression was associated with increased carotid arterial stiffness independent from the effects of traditional atherosclerosis risk factors suggests that the etiologic mechanism underlying reports of an increased cardiovascular disease risk among HIV-infected individuals might involve HIV-related immunosuppression leading to vascular dysfunction and arterial stiffening.

"Self-managed", inadequate "adherence" to antiretroviral therapy, limited to one half of standard dosages, followed by an unexpected, sustained virological and immunological success

Methods One exceptional case regards an ex-IVDA patient (p) with HIV infection known since 1985. Due to a severe HIV-related immunosuppression (CD4: 37 cells/μL), in 1997 3TC, d4T, and indinavir was effectively started, achieving after 3 months undetectable viremia and a CD4 count of 315 cells/μL, but recurring urolithiasis recommended a therapeutic shift. Since April 1997,3TC, d4T, and ritonavir were suggested for 5 years, followed by 3TC, d4T, and lopinavir-ritonavir (10 months), and 3TC, AZT, and lopinavir-ritonavir (6 years). However, all proposed regimens were voluntarily taken by our p (whose body weight was 75-80 Kg) at half-dose, as a single daily dosage, against any recommendation, although our p always maintained his “adherence” to his selfmade regimen, as assessed by monthly visits, direct drug distribution-accountabilty, and adherence questionnaires. Surprisingly, viremia remained for 12 years at non-detectable values (save one single detection of 1,260 HIV-RNA copies/μL), so that a genotypic resistance testing was never feasible, while CD4 count ranged from a nadir of 382 cells/μL (year 2001), to 525-794 cells/μL since 2003. Results A second male p with a body weight of 69-73 Kg, since 2002 took all combined antiretroviral therapy at half dosage (3TC 150 mg/day, AZT 300 mg/day, and lopinavir-ritonavir 2 cp/day for 7 years, as a single daily dose), without showing detectable viremias, and CD4 counts >500 cells/μL. A third 48-y-old male, after two changes of antiretroviral regimens due to dysmetabolism, started the fixed dose AZT-3TC-abacavir combination at half dosage (one pill/day), and since 2003 had a persistingly negative viremia, and a CD4 count always >650 cells/μL. In both these last 2 p, genotypic resistance testing was not feasible (undetectable viremia).

Human papillomavirus infection and squamous cell carcinoma of the conjunctiva

Background:Squamous cell carcinoma of the conjunctiva (SCCC) is associated with HIV-related immunosuppression, but human papillomavirus virus (HPV) is also suspected to have a role. We carried out a case–control study to assess the role of cutaneous and mucosal HPV types in SCCC, conjunctival dysplasia, and their combination (SCCC/dysplasia) in Uganda.Methods:We compared HPV prevalence in frozen biopsies from 94 SCCC cases (79 of whom were found to be HIV-positive), 39 dysplasia cases (34 HIV-positive), and 285 hospital controls (128 HIV-positive) having other eye conditions that required surgery. Highly sensitive PCR assays that detect 75 HPV types were used. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed, adjusting for, or stratifying by age, sex, and HIV status.Results:Cutaneous HPV types were detected in 45% of SCCC cases, 41% of dysplasia cases and 11% of controls. Human papillomavirus virus 5 and 8 were the most common types in SCCC, and most often occurred in combination with other types. Associations were observed between SCCC/dysplasia and detection of both single (OR=2.3; 1.2–4.4) and multiple (OR=18.3; 6.2–54.4) cutaneous HPV types, and were chiefly based on findings in HIV-positive patients. Cutaneous HPV infections were rarely observed among HIV-negative patients and the association with SCCC/dysplasia was not significant (OR=2.4; 0.6–9.6) among them. Squamous cell carcinoma of the conjunctiva/dysplasia risk and mucosal HPV types were not associated in either HIV-positive or HIV-negative patients.Conclusions:We detected cutaneous HPV types in nearly half of SCCC/dysplasia cases and often multiple types (HPV5 and 8 being most common). The role of HIV (confounder or strong enhancer of cutaneous HPV carcinogenicity) is still uncertain.

High dose prolonged treatment with nitazoxanide is not effective for cryptosporidiosis in HIV positive Zambian children: a randomised controlled trial

BackgroundTreatment of cryptosporidiosis in HIV infected children has proved difficult and unsatisfactory with no drugs having demonstrable efficacy in controlled trials except nitazoxanide. We hypothesised that a prolonged course of treatment with high dose nitazoxanide would be effective in treating cryptosporidiosis in HIV positive Zambian children.MethodsWe performed a double-blind, randomised, placebo controlled trial in paediatric patients in the UTH in Lusaka. The study included HIV positive children between one and eleven years of age if 2 out of 3 stool samples were positive for oocysts of Cryptosporidium spp. Children were given nitazoxanide suspension in a dose of 200 mg twice daily (bid) for 28 days (if 1-3 years old) or 400 mg bid for 28 days (if 4-11 years old), or matching placebo.ResultsSixty children were randomised and 52 were fully evaluated. Only five children were 4 years of age or over and received the higher dose. In the primary efficacy analysis, 11 out of 26 (42%) in the active treatment group achieved a 'Well' clinical response compared to 8 out of 26 (35%) in the placebo group. Parasitological response was declared as 'Eradicated' in 27% in the active group and 35% in the placebo group. Mortality (16/52, 31%) did not differ by treatment allocation.ConclusionWe found no significant benefit in children with cryptosporidiosis despite high dose and longer treatment duration. This is the second randomised controlled trial to suggest that in Zambian children with HIV-related immunosuppression nitazoxanide does not eradicate this infection nor provide clinical symptom reduction.Trial RegistrationThe trial was registered as ISRCTN41089957.

Kupffer cells are depleted with HIV immunodeficiency and partially recovered with antiretroviral immune reconstitution

HIV-related enhancement of gut microbial translocation is associated with progression of hepatic fibrosis. Although hepatic macrophages (Kupffer cells) clear most microbial translocation products and can be infected by HIV, their fate in HIV progression has not been carefully investigated. We studied Kupffer cell density (KCD) in 76 HIV-hepatitis C virus coinfected patients investigated at various stages of liver disease and CD4(+) lymphocyte depletion (and restoration). KCD averaged 23 cells per high-powered field (range 4.4-52.2) and was highest in portal and periportal regions as compared with centrilobular regions (P < 0.001). No differences were detected in KCD by age, liver fibrosis stage, or hepatic inflammatory score. Compared with individuals without apparent HIV-related immunosuppression, however, KCD was substantially lower in persons with lower peripheral blood CD4(+) lymphocyte counts (P = 0.027) and lowest among those with deepest CD4(+) lymphocyte nadir (P = 0.006). After the initial liver biopsy, eight patients began antiretroviral therapy and had immune restoration (> or = 2-fold increase in peripheral CD4(+) lymphocyte count) and a second histologic evaluation with a median of 36.8 months later (range 28.1-58.4 months); KCD increased in all (P = 0.007). Given the central role of Kupffer cells in controlling microbial translocation, these data suggest Kupffer cell loss needs to be considered in the pathogenesis of liver fibrosis in HIV-hepatitis C virus coinfected persons. The abundance of portal and periportal Kupffer cells is suggestive of their contribution to fibrosis in periportal regions in chronic viral hepatitis.

Predictors of CD4+ lymphocyte count among HIV-seropositive and HIV-seronegative pregnant women in Dar es Salaam, Tanzania.

To determine the predictors of CD4+ lymphocyte count among pregnant women in Dar es Salaam, Tanzania. Between 04/1995 and 03/1997, HIV-seropositive (n=1,027) and HIV-seronegative (n=280) pregnant women were interviewed to obtain socio-demographic characteristics. Later, blood samples was collected for determination of T-lymphocyte subsets and other haematological indices. CD4+ lymphocyte count was significantly higher among HIV-seronegative women (mean=770 cells/mm3, standard deviation (SD)=232 cells/mm3) than HIV-seropositive women (mean=422 cells/mm3, SD=205 cells/mm3). Most HIV-seropositive women were asymptomatic, in WHO clinical stage 1 (84.3%). Among HIV-seropositive women, total white blood count (WBC) and erythrocyte sedimentation rate (ESR) remained significantly correlated with CD4+ after adjusting for other predictors in multivariate analyses. For women of average age 25 years, the CD4+ lymphocyte count increased by about 16 cells/mm3 for each increment of 1000 WBC cells/mm3, while each 10 mm/hr increase in ESR was associated with a reduction of CD4+ lymphocyte count of about 8 cells/mm3. These results show that simple and inexpensive haematological indices cannot be recommended for use as alternative measures of HIV-related immunosuppression in this population of mainly asymptomatic women.

Does HIV/AIDS Have a Biological Impact on the Risk of Human Papillomavirus–Related Cancers?

HIV-related immunosuppression is a well-accepted, strong biological risk factor for two virus-associated cancers: Kaposi’s sarcoma, which is associated with Kaposi’s sarcoma – associated herpesvirus, and non-Hodgkin lymphoma, which is associated with Epstein – Barr virus. In fact, recognition of an extraordinarily high rate of Kaposi’s sarcoma among men who have sex with men in New York and California during the early 1980s was one of the first indications of the existence of a human immunodeficiency virus ( 1 – 3 ). Soon thereafter, high rates of non-Hodgkin lymphoma in men who have sex with men were also recognized ( 4 , 5 ), and both Kaposi’s sarcoma and non-Hodgkin lymphoma became designated as AIDS-defining malignancies in HIV-positive patients ( 6 – 8 ). It was not until the 1990s though that formal linkages between population-based AIDS registries and cancer registries were initiated ( 9 , 10 ). The AIDS – cancer match registry study in the United States ( 11 , 12 ), and similar studies in other countries ( 13 – 15 ), found that the risks for both Kaposi’s sarcoma and non-Hodgkin lymphoma were increased by at least 100-fold in persons who developed AIDS compared with the general population ( 11 , 12 ). Furthermore, there were indications of a biological gradient—one of several criteria used to assess a possible causal relationship. Specifically, the risks for both Kaposi’s sarcoma and non-Hodgkin lymphoma increased, and with lower CD4 T-cell count at time of AIDS onset ( 16 ) with increasing time after AIDS diagnosis (which is thought to be a surrogate indicator

Immune Reconstitution Visceral Leishmaniasis Presented as Hemophagocytic Syndrome in a Patient With AIDS From a Nonendemic Area: A Case Report

Visceral Leishmaniasis (VL) is endemic in the Ganges and Brahmaputra plains of India. Leishmaniasis/HIV coinfection is on the rise in India and may pose a real diagnostic and therapeutic challenge. HIV-related immunosuppression increases the risk of reactivating leishmaniasis by 100 to 1000 times and it also increases the risk of drug resistant leishmaniasis. Immune reconstitution VL is not very well reported in literature. Hemophagocytosis is known to occur with various infectious agents like viruses, bacteria, and parasites, but is rare to occur with leishmaniasis. Here the authors describe a case of VL presenting as immune reconstitution disease and hemophagocytosis in an HIV infected patient coming from a nonendemic area.

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).

Assessment of Liver Fibrosis by Transient Elastography in Persons with Hepatitis C Virus Infection or HIV–Hepatitis C Virus Coinfection

Transient elastography is a novel, noninvasive method for staging liver fibrosis. We compared elastography with histologic methods among hepatitis C virus (HCV)-infected and human immunodeficiency virus (HIV)-HCV-coinfected participants in an urban, predominantly black study population. Participants recruited from the AIDS Linked to the Intravenous Experience and the Johns Hopkins HIV Clinical Cohort studies underwent elastography to determine liver stiffness measurements. Liver biopsy specimens were staged F0-F4 in accordance with the Metavir score. Diagnostic accuracy and determination of liver stiffness cutoff values, compared with histologic methods, were determined by receiver operating characteristic analysis. Logistic regression methods identified parameters associated with discordant classification status. Of 192 participants, 139 (72%) were coinfected with HIV and HCV, 121 (63%) had insignificant fibrosis, and 48 (25%) had cirrhosis. Overall, the area-under-the-curve receiver operating characteristic was 0.87 for detection of both significant fibrosis (95% confidence interval, 0.82-0.92) and cirrhosis (95% confidence interval, 0.81-0.93). With use of cutoff values of 9.3 kPa for fibrosis and 12.3 kPa for cirrhosis, 79%-83% of participants were correctly classified by liver stiffness measurement (compared with histologic methods); accuracy appeared to be higher among HIV-uninfected participants than among HIV-infected participants. Most discordance occurred when liver stiffness measurements indicated liver disease and histologic examination did not (in 16% of participants); the patients with these discordant results were more likely to have attributes that increased the odds of significant fibrosis, such as elevated serum fibrosis markers or HIV-related immunosuppression, compared with persons in whom low fibrosis was predicted by both examination of a biopsy specimen and elastography. For most HCV-infected persons, fibrosis stage predicted by elastography is similar to that predicted by examination of a biopsy specimen. Elastography-based measurement of liver stiffness holds promise to expand liver disease screening and monitoring, particularly among injection drug users.

Varicella Zoster Meningitis in a Pregnant Woman with Acquired Immunodeficiency Syndrome

Between 6000 and 7000 women in the United States infected with human immunodeficiency virus (HIV) give birth annually. It is well known that HIV-related immunosuppression significantly increases the risk for acquiring opportunistic infections (OIs). However, there is limited information regarding the relationship of pregnancy in the setting of HIV/AIDS infection, subsequent development of OIs, and maternal and fetal outcomes. A pregnant 36-year-old woman with AIDS was diagnosed with varicella zoster meningitis. Weight-based therapy with acyclovir was initiated with clinical improvement in symptoms. Care of a pregnant HIV-infected patient with an OI poses a unique diagnostic and therapeutic challenge for clinicians. Early diagnosis and initiation of appropriate treatment may provide an opportunity to improve both maternal and fetal outcomes.

Human Immunodeficiency Virus–Associated Renal Cell Carcinoma: A Transatlantic Case Series

Objective The spectrum of diseases associated with human immunodeficiency virus (HIV) infection has changed dramatically following the introduction of highly active antiretroviral therapy (HAART). Non–AIDSdefining cancers, including renal cell carcinoma (RCC), are being recognized increasingly in this population. Our aim was to describe the risk factors, clinical findings, pathology, and response to therapy of RCC in patients infected with HIV. Patients and Methods We identified 9 men with HIV infection who developed RCC. Data regarding their HIV status, RCC risk factors, clinical presentation, and pathology were collected. A detailed retrospective chart review focusing on the course of their malignancy, response to therapy, and outcome was performed. Results Renal cell carcinoma was diagnosed in patients with a median age of 48 years, and most had a history of tobacco use. No association between HIV-related immunosuppression (mean CD4 count, 301 cells/mm 3) and the development, clinical presentation, pathology, or behavior of RCC was identified. Long-term survival correlated with early nephrectomy, and the use of interleukin-2 therapy for advanced RCC was not additive. A total of 5 patients died, 1 from a pulmonary embolism and 4 from disseminated RCC. Conclusion Renal cell carcinoma should be included in the expanding array of non–AIDS-defining malignancies that develop during the course of HIV infection. Acknowledging the inherent limitations of our small study, these data show that the clinical presentation and behavior of RCC in patients with HIV appear similar to that of the HIV-negative population and that chronic immunosuppression plays a lesser role than age and exposure to risk factors in this setting.

Is HIV infection associated with an increased risk for cholera? Findings from a case–control study in Mozambique

As residents of sub-Saharan Africa are at high risk for HIV and cholera, it is biologically plausible that immune suppression caused by HIV infection predisposes to cholera. Our aim was to assess the potential association between both diseases. We conducted a case-control study in Beira, Mozambique, a high-risk area for HIV and cholera. Between 1 January 2005 and 30 June 2006, experienced counsellors invited 132 suspected cholera cases and 528 age- and sex-matched controls to an HIV counselling and testing centre. Forty (30%) of the invited cases and 127 (24%) of the invited controls came for HIV testing. No significant differences in demographic and socio-economic baseline characteristics were detected between participants and non-participants. Twenty five of 167 (15%) individuals who underwent testing were found HIV-positive. The probability of a positive HIV-test was highest in participants between 40 and 49 years; 6 of 14 (43%) tested HIV-positive. Nine of 40 (23%) cholera cases were found to be HIV-infected compared with 16 of 127 (13%) controls (adjusted odds ratio 2.6; 95% CI 0.9-7.5; P = 0.08). The findings suggest that in a cholera-endemic area, HIV infection is associated with an increased risk for cholera. More research in HIV endemic settings is needed to confirm the findings and to explore the effect of HIV-related immunosuppression on the transmission of cholera.

Human Immunodeficiency Virus-Related Microbial Translocation and Progression of Hepatitis C

Human immunodeficiency virus (HIV)-1 infection has been associated with enhanced microbial translocation, and microbial translocation is a mechanism through which alcohol and some enteric conditions cause liver disease. We hypothesized that HIV promotes liver disease by enhancing microbial translocation. We studied human cohorts in which hepatitis C virus (HCV) and HIV outcomes were carefully characterized. HIV-related CD4(+) lymphocyte depletion was strongly associated with microbial translocation as indicated by elevated levels of circulating lipopolysaccharide (LPS), LPS-binding protein, soluble CD14, and fucose-binding lectin (AAL) reactive to immunoglobulin G specific for the alpha-galactose epitope and suppressed levels of endotoxin core antibodies (EndoCAb IgM) in HIV-infected subjects compared with the same persons before they had HIV infection and compared with HIV-uninfected subjects. The same measures of microbial translocation were strongly associated with HCV-related liver disease progression (cirrhosis), eg, LPS, odds ratio, 19.0 (P = .002); AAL, odds ratio, 27.8 (P < .0001); in addition, levels of LPS were elevated prior to recognition of cirrhosis. Microbial translocation may be a fundamental mechanism through which HIV accelerates progression of chronic liver disease.

The interaction between HIV and malaria in Africa

HIV and malaria kill millions of people every year. They share a common geographic distribution, and both cause far more disease and death in sub-Saharan Africa than they do in the rest of the world. Many epidemiologic studies have suggested that HIV and malaria coexist independently, but some recent reports describe synergistic interactions between them. People living with HIV infection who do not have pre-existing immunity to malaria experience a marked increase in malaria severity. But for those who have acquired immunity through natural exposure to malaria, HIV-related immunosuppression is associated with only a modest increase in clinical malaria, which may be explained in part by more frequent nonmalaria febrile episodes. The effect of malaria infection on HIV disease progression due to increased viral replication may be important but has not yet been fully explored.

A case for treating high hepatitis B DNA levels before starting HIV therapy

A case for treating high hepatitis B DNA levels before starting HIV therapy

Reactivation of latent hepatitis B virus infection with HIV-related immunosuppression

The effect of HIV-related immunosuppression and antiretroviral therapy on the reactivation of latent hepatitis B virus (HBV) infection is unclear. We report four patients with advanced HIV-related immunosuppression and abnormal liver function tests who had evidence of HBV reactivation. Reclearance of hepatitis B occurred in two cases with HIV treatment regimens not containing lamivudine, suggesting that improved immune function may be responsible. In three cases, HBV reactivation was recognized during investigation for abnormal liver function initially attributed to drug toxicity. The possibility of HBV reactivation must be considered in the differential diagnosis of abnormal liver function in cases with advanced HIV.

Does Severity of HIV Disease in HIV-Infected Mothers Affect Mortality and Morbidity among Their Uninfected Infants?

Rates of perinatal human immunodeficiency virus (HIV) transmission are higher among HIV-infected mothers with more advanced disease, but effects of maternal disease on HIV-uninfected offspring are unclear. We investigated the hypothesis that the severity of HIV disease and immune dysfunction among mothers is associated with increased morbidity and mortality among their uninfected infants. In a birth cohort of 620 HIV-uninfected infants born to HIV-infected mothers in Lusaka, Zambia, we investigated associations between markers of more advanced maternal HIV disease and child mortality, hospital admissions, and infant weight through 4 months of age. Mortality in the cohort of uninfected infants was 4.6% (95% confidence interval [CI], 2.8-6.3) through 4 months of age. Infants of mothers with CD4+ T cell counts of <350 cells/microL were more likely to die (hazard ratio [HR], 2.87; 95% CI, 1.03-8.03) and were more likely to be hospitalized (HR, 2.28; 95% CI, 1.17-4.45), after adjusting for other factors, including maternal death and low birth weight. The most common cause of infant death and hospitalization was pneumonia and/or sepsis. A maternal viral load of >100,000 copies/mL was associated with significantly lower child weight through 4 months of age. Children born to HIV-infected mothers with advanced disease who escaped perinatal or early breastfeeding-related HIV infection are nonetheless at high risk of mortality and morbidity during the first few months of life. HIV-related immunosuppression appears to have adverse consequences for the health of infants, in addition to risks of vertical transmission.

Aerodigestive cancers in HIV infection

Aerodigestive (lung, head and neck) cancers are among the most prevalent and deadly neoplasms worldwide, and the incidence rates are rising. Given the improvements in life expectancy of persons with HIV/AIDS when treated with highly active antiretroviral agents, persons with HIV infection are therefore increasingly likely to develop these malignancies. This chapter focuses on the epidemiology of these malignancies and reviews the most recent literature and current understanding of the causes and treatment of these malignancies in HIV-positive populations. Aerodigestive neoplasms in patients with HIV infection are associated with younger age at diagnosis, cigarette smoking, advanced stage at presentation, and a more aggressive clinical course. The causes of these cancers, aside from the traditional risk factors of tobacco and alcohol exposure, are not clear. Although these neoplasms are non-AIDS defining, factors that might contribute to risk include HIV-related immunosuppression and co-infection with high-risk human papillomavirus subtypes. With continued improvements in therapies for HIV, the expected increase in incidence and mortality of persons with HIV infection from aerodigestive malignancies will likely become a major public health concern. Given the younger age of HIV-infected patients with these malignancies and the apparently higher rates of smoking among HIV-positive individuals, aggressive smoking cessation efforts should be directed to this high-risk population.