Late-stage HIV Disease Research Articles

Early mortality after late initiation of antiretroviral therapy in the TREAT Asia HIV Observational Database (TAHOD) of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Asia-Pacific.

Early mortality among those still initiating antiretroviral therapy (ART) with advanced stages of HIV infection in resource-limited settings remains high despite recommendations for universal HIV treatment. We investigated risk factors associated with early mortality in people living with HIV (PLHIV) starting ART at low CD4 levels in the Asia-Pacific. PLHIV enrolled in the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) who initiated ART with a CD4 count<100cells/μL between 2003 and 2018 were included in the study. Early mortality was defined as death within 1 year of ART initiation. PLHIV in follow-up for > 1 year were censored at 12months. Competing risk regression was used to analyse risk factors with loss to follow-up as a competing risk. A total of 1813 PLHIV were included in the study, of whom 74% were male. With 73 (4%) deaths, the overall first-year mortality rate was 4.27 per 100 person-years (PY). Thirty-eight deaths (52%) were AIDS-related, 10 (14%) were immune reconstituted inflammatory syndrome (IRIS)-related, 13 (18%) were non-AIDS-related and 12 (16%) had an unknown cause. Risk factors included having a body mass index (BMI)<18.5 [sub-hazard ratio (SHR) 2.91; 95% confidence interval (CI) 1.60-5.32] compared to BMI 18.5-24.9, and alanine aminotransferase (ALT)≥5 times its upper limit of normal (ULN) (SHR 6.14; 95% CI 1.62-23.20) compared to ALT<5 times its ULN. A higher CD4 count (51-100cells/μL: SHR 0.28; 95% CI 0.14-0.55; and >100cells/μL: SHR 0.12; 95% CI 0.05-0.26) was associated with reduced hazard for mortality compared to CD4 count≤25cells/μL. Fifty-two per cent of early deaths were AIDS-related. Efforts to initiate ART at CD4 counts > 50cell/μL are associated with improved short-term survival rates, even in those with late stages of HIV disease.

Causes of hospitalization and predictors of HIV-associated mortality at the main referral hospital in Sierra Leone: a prospective study

BackgroundHIV infection is a growing public health problem in Sierra Leone and the wider West Africa region. The countrywide HIV prevalence was estimated at 1.7% (67,000 people), with less than 30% receiving life-saving ART in 2016. Thus, HIV-infected patients tend to present to health facilities late, with high mortality risk.MethodsWe conducted a prospective study of HIV inpatients aged ≥15 years at Connaught Hospital in Freetown—the main referral hospital in Sierra Leone—from July through September 2017, to assess associated factors and predictors of HIV-related mortality.ResultsOne hundred seventy-three HIV inpatients were included, accounting for 14.2% (173/1221) of all hospital admissions during the study period. The majority were female (59.5%, 70/173), median age was 34 years, with 51.4% (89/173) of them diagnosed with HIV infection for the first time during the current hospitalization. The most common admitting diagnoses were anemia (48%, 84/173), tuberculosis (24.3%, 42/173), pneumonia (17.3%, 30/173) and diarrheal illness (15.0%, 26/173). CD4 count was obtained in 64.7% (112/173) of patients, with median value of 87 cells/μL (IQR 25–266), and was further staged as severe immunosuppression: CD4 < 100 cells/μL (50%, 56/112); AIDS: CD4 < 200 cells/μL (69.6%, 78/112); and late-stage HIV disease: CD4 < 350 cells/μL (83%, 93/112). Fifty-two patients (30.1%, 52/173) died during hospitalization, 23% (12/52) of them within the first week. The leading causes of death were anemia (23.1%, 12/52), pneumonia (19.2%, 10/52), diarrheal illness (15.4%, 8/52) and tuberculosis (13.6%, 7/52). Neurological symptoms, i.e., loss of consciousness (p = 0.04) and focal limb weakness (p = 0.04); alcohol use (p = 0.01); jaundice (p = 0.02); cerebral toxoplasmosis (p = 0.01); and tuberculosis (p = 0.04) were significantly associated with mortality; however, only jaundice (AOR 0.11, 95% CI [0.02–0.65]; p = 0.01) emerged as an independent predictor of mortality.ConclusionHIV-infected patients account for a substantial proportion of admissions at Connaught Hospital, with a high morbidity and in-hospital mortality burden. These findings necessitate the implementation of specific measures to enhance early HIV diagnosis and expand treatment access to all HIV-infected patients in Sierra Leone.

Factors Associated with High-Grade Anal Intraepithelial Lesion in HIV-Positive Men in a Southern U.S. City.

The incidence of anal cancer is increased in HIV-infected patients compared with the general population. Risk factors associated with the anal cancer precursor, high-grade squamous intraepithelial lesion (HSIL), have not been extensively studied in an urban black population with late-stage HIV disease. We performed a retrospective chart review of HIV-infected men at the Grady Ponce de Leon Center HIV Clinic (Atlanta, GA) referred for high-resolution anoscopy (HRA), a procedure where anal tissue is examined under magnification and abnormal areas are biopsied. Between December 2013 and September 2015, 147 men underwent HRA: 72% were black, and 94% were men who have sex with men. CD4 count closest to time of HRA was a median 325 cells/mm3 (interquartile range 203-473), and 69% had an undetectable HIV viral load. Ninety-four percent had abnormal anal cytology [80% atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (LSIL) and 20% atypical squamous cells, cannot exclude HSIL/HSIL], and 97% had abnormal histology (35% LSIL, 65% HSIL). Statistically significant variables associated with HSIL included number of biopsies [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.13-2.14] and having ≥1 high-grade anal cytology in the last 12 months (OR 3.76, 95% CI 1.38-10.23). No significant association was found between HSIL and CD4, HIV viral load, or recent sexually transmitted infection. In this population, the burden of anal HSIL was extremely high, regardless of most recent anal cytology result. In newly diagnosed HIV-infected men with no history of anal cancer screening, performing HRA as primary anal cancer screening instead of cytology appears to be a viable option.

Effect of ageing on neurocognitive function by stage of HIV infection: evidence from the Multicenter AIDS Cohort Study

The demographics of the HIV epidemic in the USA have shifted towards older age. We aimed to establish the relationship between the processes of ageing and HIV infection in neurocognitive impairment. With longitudinal data from the Multicenter AIDS Cohort Study, a long-term prospective cohort study of the natural and treated history of HIV infection among men who have sex with men in the USA, we examined the effect of ageing, HIV infection (by disease stage), and their interaction on five neurocognitive domains: information processing speed, executive function, episodic memory, working memory, and motor function. We controlled for duration of serostatus in a subanalysis, as well as comorbidities and other factors that affect cognition. Analyses were by linear mixed models for longitudinal data. 5086 participants (47 886 visits) were included in the analytic sample (2278 HIV-seropositive participants contributed 20 477 visits and 2808 HIV-seronegative control participants contributed 27 409 visits). In an a-priori multivariate analysis with control variables including comorbidities and time since seroconversion, significant, direct negative effects of ageing were noted on all neurocognitive domains (p<0·0001 for all). Similar effects were noted for late-stage HIV disease progression on information processing speed (p=0·002), executive function (p<0·0001), motor function (p<0·0001), and working memory (p=0·001). Deleterious interaction effects were also noted in the domains of episodic memory (p=0·03) and motor function (p=0·02). A greater than expected effect of ageing on episodic memory and motor function with advanced stages of HIV infection suggests that these two domains are most susceptible to the progression of neurocognitive impairment caused by ageing in individuals with HIV. This deficit pattern suggests differential damage to the hippocampus and basal ganglia (specifically nigrostriatal pathways). Older individuals with HIV infection should be targeted for regular screening for HIV-associate neurocognitive disorder, particularly with tests referable to the episodic memory and motor domains. National Institute of Mental Health.

Continuous Antigenic Stimulation of DO11.10 TCR Transgenic Mice in the Presence or Absence of IL-1β: Possible Implications for Mechanisms of T Cell Depletion in HIV Disease.

Untreated HIV disease is associated with chronic immune activation and CD4(+) T cell depletion. A variety of mechanisms have been invoked to account for CD4(+) T cell depletion in this setting, but the quantitative contributions of these proposed mechanisms over time remain unclear. We turned to the DO11.10 TCR transgenic mouse model, where OVA is recognized in the context of H-2(d), to explore the impact of chronic antigenic stimulation on CD4(+) T cell dynamics. To model dichotomous states of persistent Ag exposure in the presence or absence of proinflammatory stimulation, we administered OVA peptide to these mice on a continuous basis with or without the prototypic proinflammatory cytokine, IL-1β. In both cases, circulating Ag-specific CD4(+) T cells were depleted. However, in the absence of IL-1β, there was limited proliferation and effector/memory conversion of Ag-specific T cells, depletion of peripheral CD4(+) T cells in hematolymphoid organs, and systemic induction of regulatory Foxp3(+)CD4(+) T cells, as often observed in late-stage HIV disease. By contrast, when OVA peptide was administered in the presence of IL-1β, effector/memory phenotype T cells expanded and the typical symptoms of heightened immune activation were observed. Acknowledging the imperfect and incomplete relationship between Ag-stimulated DO11.10 TCR transgenic mice and HIV-infected humans, our data suggest that CD4(+) T cell depletion in the setting of HIV disease may reflect, at least in part, chronic Ag exposure in the absence of proinflammatory signals and/or appropriate APC functions.

HIV/AIDS Histories: Community Service Organizations and the Direct-Action AIDS Movement in Documentary Film

HIV/AIDS Histories: Community Service Organizations and the Direct-Action AIDS Movement in Documentary Film Richard A. McKay We Were Here( Peccadillo Pictures, 2011). Directed and produced by David Weissman. 89 minutes. United in Anger: A History of ACT UP( United in Anger, Inc., 2012). Directed by Jim Hubbard. Produced by Sarah Schulman. 93 minutes. How to Survive a Plague( Network Releasing, 2012). Directed by David France. Produced by Howard Gertler and David France. 105 minutes. With releases timed to accompany the thirtieth anniversary of the recognition in 1981 of a syndrome that would become known as AIDS, and the twenty-fifth anniversary of the formation of the AIDS Coalition to Unleash Power (ACT UP)—the best-known direct-action AIDS protest group—three new documentary films offer compelling and contrasting accounts of the worst years of the American HIV/ AIDS epidemic. Covering the fifteen-year period before the development of effective combination antiretroviral therapy in 1996, the films chart the initiatives that emerged from the nation’s lesbian and gay communities in response to the deaths of tens of thousands amidst widespread social apathy and governmental neglect. We Were Herefocuses on the changes wrought by the arrival of HIV in San Francisco, in particular the creation of a remarkably successful and diverse patchwork of community-based AIDS service organizations in the 1980s. By contrast, United in Angerand How to Survive a Plaguefocus predominantly on New York, and on the political activism, media savvy, and emotional dynamics of ACT UP from 1987 onward as this group fought for more effective and more widely available HIV treatment, prevention, and support for people living with AIDS. David Weissman’s We Were Herefeatures five San Francisco residents—Paul, a political activist and community organizer; Guy, a flower seller on Castro Street; Eileen, a nurse with a background in the women’s movement; Ed, an educator and caregiver; and Daniel, an artist and entrepreneur. It follows them from their arrival in the Bay Area during the 1970s and through their life-changing encounters with the disease that silently established itself in the city at about the same time. With their on-camera testimonies providing a narrative frame for a rich montage of archival photographs, documents, and film footage, the documentary unfolds more or less chronologically. It explores the community’s gradual realization of the scale of the medical disaster, the support and rejection of patients by family and friends, the constant obituaries in local newspapers, hospital treatment and experimental drug trials, and the network of volunteer organizations that sprang up to care for those who were sick and dying. Weissman and his editor and co-director, Bill Weber, set up a slow, elegiac pace for the film, regularly fading to black and employing skilful dissolves to forge powerful associations between still images, a technique that is most evident when depicting the ravages of HIV and [End Page 734]its opportunistic infections on young gay men. While such visual representations of the syndrome were at one time strongly protested by AIDS activists, it struck me that—in an era when late-stage HIV disease is much less visible in North America—a visual reminder of the infection’s devastating power might be timely for a new generation of viewers. The film’s narrators are engaging, with two moments in particular resonating with my own experience of interviewing survivors of the epidemic. One was the heart-wrenching immediacy and raw emotions captured when Daniel recalls the “avalanche” of deaths he endured in rapid succession; in addition to many friends dying, the epidemic claimed the lives of two successive lovers while he was struggling with his own HIV infection. Another striking moment was Ed’s powerful description of how the epidemic created openings in the gay community for caregiving to come to the fore. These changes allowed people like him to find and carve out places for themselves that had hitherto not been possible; thus, opportunities may be present in even the bleakest of moments. While the film’s coverage includes candlelight marches, the rise of a more confrontational AIDS activism, and the eventual development of effective antiretroviral therapy, the film’s main...

Risk factors for delayed entrance into care after diagnosis among patients with late-stage HIV disease in southern Vietnam.

BackgroundWe surveyed HIV patients with late-stage disease in southern Vietnam to determine if barriers to access and service quality resulted in late HIV testing and delays from initial diagnosis to entry into HIV care.Methodology196 adult patients at public HIV clinics with CD4 counts less than 250 cells/mm3 completed a standardized questionnaire. We used multivariate analysis to determine risk factors for delayed entry into care, defined as >3 months time from diagnosis to registration.ResultsCommon reasons for delayed testing were feeling healthy (71%), fear of stigma and discrimination in the community (43%), time conflicts with work or school (31%), did not want to know if infected (30%), and fear of lack of confidentiality (27%). Forty-five percent of participants delayed entry into care with a median CD4 count of 65 cells/mm3. The most common reasons for delayed entry were feeling healthy (51%), fear of stigma and discrimination in the community (41%), time conflicts with work or school (33%), and fear of lack of confidentiality (26%). Independent predictors for delayed entry were feeling healthy (aOR 3.7, 95% CI 1.5–9.1), first positive HIV test at other site (aOR 2.9, CI 1.2–7.1), history of injection drug use (IDU) (aOR 2.9, 95% CI 1.1–7.9), work/school conflicts (aOR 4.3, 95% CI 1.7–10.8), prior registration at another clinic (aOR 77.4, 95% CI 8.6–697), detention or imprisonment (aOR 10.3, 95% CI 1.8–58.2), and perceived distance to clinic (aOR 3.7, 95% CI 1.0–13.7).ConclusionDelayed entry into HIV care in Vietnam is common and poses a significant challenge to preventing AIDS and opportunistic infections, decreasing mortality, and reducing HIV transmission. Improved linkages between testing and care are needed, particularly for patients who feel healthy, as well as incarcerated and drug-using populations who may face structural and social barriers to accessing care.

Successful outcome of renal transplantation in a child with HIV-associated nephropathy

Classical HIV-associated nephropathy (HIVAN) was first described before the advent of highly active antiretroviral therapy in late stages of HIV disease with high viral load and low CD4 cell count....

Trends of CD4 cell count levels at the initiation of antiretroviral therapy over time and factors associated with late initiation of antiretroviral therapy among Asian HIV‐positive patients

IntroductionAlthough antiretroviral therapy (ART) has been rapidly scaled up in Asia, most HIV-positive patients in the region still present with late-stage HIV disease. We aimed to determine trends of pre-ART CD4 levels over time in Asian HIV-positive patients and to determine factors associated with late ART initiation.MethodsData from two regional cohort observational databases were analyzed for trends in median CD4 cell counts at ART initiation and the proportion of late ART initiation (CD4 cell counts <200 cells/mm3 or prior AIDS diagnosis). Predictors for late ART initiation and mortality were determined.ResultsA total of 2737 HIV-positive ART-naïve patients from 22 sites in 13 Asian countries and territories were eligible. The overall median (IQR) CD4 cell count at ART initiation was 150 (46–241) cells/mm3. Median CD4 cell counts at ART initiation increased over time, from a low point of 115 cells/mm3 in 2008 to a peak of 302 cells/mm3 after 2011 (p for trend 0.002). The proportion of patients with late ART initiation significantly decreased over time from 79.1% before 2007 to 36.3% after 2011 (p for trend <0.001). Factors associated with late ART initiation were year of ART initiation (e.g. 2010 vs. before 2007; OR 0.40, 95% CI 0.27–0.59; p<0.001), sex (male vs. female; OR 1.51, 95% CI 1.18–1.93; p=0.001) and HIV exposure risk (heterosexual vs. homosexual; OR 1.66, 95% CI 1.24–2.23; p=0.001 and intravenous drug use vs. homosexual; OR 3.03, 95% CI 1.77–5.21; p<0.001). Factors associated with mortality after ART initiation were late ART initiation (HR 2.13, 95% CI 1.19–3.79; p=0.010), sex (male vs. female; HR 2.12, 95% CI 1.31–3.43; p=0.002), age (≥51 vs. ≤30 years; HR 3.91, 95% CI 2.18–7.04; p<0.001) and hepatitis C serostatus (positive vs. negative; HR 2.48, 95% CI 1.−4.36; p=0.035).ConclusionsMedian CD4 cell count at ART initiation among Asian patients significantly increases over time but the proportion of patients with late ART initiation is still significant. ART initiation at higher CD4 cell counts remains a challenge. Strategic interventions to increase earlier diagnosis of HIV infection and prompt more rapid linkage to ART must be implemented.

Complex care needs of patients with late-stage HIV disease: A retrospective study

This retrospective chart review provides a profile of an emerging population of vulnerable HIV patients with complex comorbidities. Data were abstracted from all 83 patients admitted in 2008 to Casey House, a community-based hospital dedicated to supportive and palliative care for persons with HIV in Toronto, Canada. We describe patient characteristics, including medical and psychiatric conditions, and use a Venn diagram and case study to illustrate the frequency and reality of co-occurring conditions that contribute to the complexity of patients' health and health care needs. The mean age at admission was 49.2 years (SD = 10.5). Sixty-seven patients (80.7%) were male. Patients experienced a mean of 5.9 medical comorbidities (SD = 2.3) and 1.9 psychiatric disorders (lifetime Axis I diagnoses). Forty patients (48.2%) experienced cognitive impairment including HIV-associated dementia. Patients were on a mean of 11.5 (SD = 5.3) medications at admission; 74.7% were on antiretroviral medications with 55.0% reporting full adherence. Current alcohol and drug use was common with 50.6% reporting active use at admission. Our Venn diagram illustrates the breadth of complexity in the clients with 8.4% of clients living in unstable housing with three or more medical comorbidities and two or more psychiatric diagnoses. Comprehensive HIV program planning should include interventions that can flexibly adapt to meet the multidimensional and complex needs of this segment of patients. Researchers, policy-makers, and clinicians need to have greater awareness of overlapping medical, psychiatric and psychosocial comorbidities. Inclusion of the needs of these most vulnerable patients in the development of evidence-based guidelines is an important step for effectively treating, preventing, and planning for the future of HIV/AIDS care.

Complex care needs of patients with late-stage HIV disease: A retrospective study

This retrospective chart review provides a profile of an emerging population of vulnerable HIV patients with complex comorbidities. Data were abstracted from all 87 patients admitted in 2008 to Casey House, a community-based hospital dedicated to supportive and palliative care for persons with HIV in Toronto, Canada. We describe patient characteristics, including medical and psychiatric conditions, and use a Venn diagram and case study to illustrate the frequency and reality of co-occurring conditions that contribute to the complexity of patients’ health and health care needs. The mean age at admission was 48.9 years (SD = 10.5). Eighty percent were male. Patients experienced a mean of 5.8 medical comorbidities (SD = 2.3) and 1.9 psychiatric disorders (lifetime axis I diagnoses). Forty-one patients (47%) experienced cognitive impairment including HIV-associated dementia. Patients were on a mean of 11.8 (SD = 5.3) medications at admission; 74% were on antiretroviral medications with 55% reporting full adherence. Current alcohol and drug use was common with 54% reporting active use at admission. Our Venn diagram illustrates the breadth of complexity in the clients with 9% of clients living in unstable housing with three or more medical comorbidites and two or more psychiatric diagnoses. Comprehensive HIV program planning should include interventions that can flexibly adapt to meet the multidimensional and complex needs of this segment of patients. Researchers, policymakers and clinicians need to have greater awareness of overlapping medical, psychiatric and psychosocial comorbidities. Inclusion of the needs of these most vulnerable patients in the development of evidence based guidelines is an important step for effectively treating, preventing and planning for the future of HIV/AIDS care.

Risk Factors for Late-Stage HIV Disease Presentation at Initial HIV Diagnosis in Durban, South Africa

BackgroundAfter observing persistently low CD4 counts at initial HIV diagnosis in South Africa, we sought to determine risk factors for late-stage HIV disease presentation among adults.MethodsWe surveyed adults prior to HIV testing at four outpatient clinics in Durban from August 2010 to November 2011. All HIV-infected adults were offered CD4 testing, and late-stage HIV disease was defined as a CD4 count <100 cells/mm3. We used multivariate regression models to determine the effects of sex, emotional health, social support, distance from clinic, employment, perceived barriers to receiving healthcare, and foregoing healthcare to use money for food, clothing, or housing (“competing needs to healthcare”) on presentation with late-stage HIV disease.ResultsAmong 3,669 adults screened, 830 were enrolled, newly-diagnosed with HIV and obtained a CD4 result. Among those, 279 (33.6%) presented with late-stage HIV disease. In multivariate analyses, participants who lived ≥5 kilometers from the test site [adjusted odds ratio (AOR) 2.8, 95% CI 1.7–4.7], reported competing needs to healthcare (AOR 1.7, 95% CI 1.2–2.4), were male (AOR 1.7, 95% CI 1.2–2.3), worked outside the home (AOR 1.5, 95% CI 1.1–2.1), perceived health service delivery barriers (AOR 1.5, 95% CI 1.1–2.1), and/or had poor emotional health (AOR 1.4, 95% CI 1.0–1.9) had higher odds of late-stage HIV disease presentation.ConclusionsIndependent risk factors for late-stage HIV disease presentation were from diverse domains, including geographic, economic, demographic, social, and psychosocial. These findings can inform various interventions, such as mobile testing or financial assistance, to reduce the risk of presentation with late-stage HIV disease.

Belief in AIDS-Related Conspiracy Theories and Mistrust in the Government: Relationship With HIV Testing Among At-Risk Older Adults

One in 4 persons living with HIV/AIDS is an older adult (age 50 or older); unfortunately, older adults are disproportionately diagnosed in late stages of HIV disease. Psychological barriers, including belief in AIDS-related conspiracy theories (e.g., HIV was created to eliminate certain groups) and mistrust in the government, may influence whether adults undergo HIV testing. We examined relationships between these factors and recent HIV testing among at-risk, older adults. This was a cross-sectional study among older adults enrolled in a large venue-based study. None had a previous diagnosis of HIV/AIDS; all were seeking care at venues with high HIV prevalence. We used multiple logistic regression to estimate the associations between self-reported belief in AIDS-related conspiracy theories, mistrust in the government, and HIV testing performed within the past 12 months. Among the 226 participants, 30% reported belief in AIDS conspiracy theories, 72% reported government mistrust, and 45% reported not undergoing HIV testing within the past 12 months. Belief in conspiracy theories was positively associated with recent HIV testing (adjusted odds ratio [OR] = 1.94, 95% confidence interval [CI] = 1.05-3.60), whereas mistrust in the government was negatively associated with testing (OR = 0.43, 95% CI = 0.26-0.73). Psychological barriers are prevalent among at-risk older adults seeking services at venues with high HIV prevalences and may influence HIV testing. Identifying particular sources of misinformation and mistrust would appear useful for appropriate targeting of HIV testing strategies.

Complex care needs of patients with late-stage HIV disease: A retrospective study

This retrospective chart review provides a profile of an emerging population of vulnerable HIV patients with complex comorbidities. Data were abstracted from all 87 patients admitted in 2008 to Casey House, a community-based hospital dedicated to supportive and palliative care for persons with HIV in Toronto, Canada. We describe patient characteristics, including medical and psychiatric conditions, and use a Venn diagram and case study to illustrate the frequency and reality of co-occurring conditions that contribute to the complexity of patients’ health and health care needs. The mean age at admission was 48.9 years (SD = 10.5). Eighty percent were male. Patients experienced a mean of 5.8 medical comorbidities (SD = 2.3) and 1.9 psychiatric disorders (lifetime axis I diagnoses). Forty-one patients (47%) experienced cognitive impairment including HIV-associated dementia. Patients were on a mean of 11.8 (SD = 5.3) medications at admission; 74% were on antiretroviral medications with 55% reporting full adherence. Current alcohol and drug use was common with 54% reporting active use at admission. Our Venn diagram illustrates the breadth of complexity in the clients with 9% of clients living in unstable housing with three or more medical comorbidites and two or more psychiatric diagnoses. Comprehensive HIV program planning should include interventions that can flexibly adapt to meet the multidimensional and complex needs of this segment of patients. Researchers, policymakers and clinicians need to have greater awareness of overlapping medical, psychiatric and psychosocial comorbidities. Inclusion of the needs of these most vulnerable patients in the development of evidence based guidelines is an important step for effectively treating, preventing and planning for the future of HIV/AIDS care.

Determinants of Late-Stage HIV Disease at Diagnosis in Singapore, 1996 to 2009

The delay in HIV diagnosis has been identified as a significant reason for late presentation to medical care. This research aims to elucidate the significant determinants of late-stage HIV infection in Singapore between 1996 and 2009, after the advent of highly active anti-retroviral therapies. We included 3735 patients infected via sexual mode of transmission from the National HIV Registry diagnosed between 1996 and 2009. Late-stage HIV infection is defined as CD4 count less than 200 mm(3) or AIDS-defining opportunistic infections at fi rst diagnosis or within one year of HIV diagnosis. We determined independent epidemiological risk factors for late-stage HIV infection at first diagnosis using multivariate logistic regression. Multivariate analysis showed that older age corresponded significantly with increasing odds of late-stage HIV infection. Compared to persons diagnosed at 15 to 24 years of age, those diagnosed at age 55 years and above were associated with 5-fold increased likelihood of late-stage infection (adjusted odds ratio (AOR): 5.17; 95% CI, 3.21 to 8.33). Chinese ethnicity, singlehood, and non-professional occupations were also significantly associated with late-stage HIV infection. Persons detected in the course of medical care had over 3.5 times the odds of late-stage infection (AOR: 3.55; 95% CI, 2.71 to 4.65). Heterosexual mode of transmission and having sex workers and social escorts as sexual partners, were the other epidemiological risk factors with significant associations. The findings of this study emphasises the need to increase HIV awareness and to encourage early and regular HIV testing among at-risk persons.

Successful outcome of first paediatric renal transplant for HIV associated nephropathy

<h3>Aims</h3> Classical HIV-associated nephropathy (HIVAN) was first described before the advent of highly active anti-retroviral therapy (HAART) in late stages of HIV disease with high viral load and low CD4+ cell count. Renal transplantation guidelines for adults with HIVAN have been developed1 with comparable patient and graft survival.23 We report the successful outcome of living related renal transplantation in an 8 year old girl (AB; name changed) on haemodialysis due to HIVAN. <h3>Patients and methods</h3> AB is a vertically HIV-infected girl who was initially lost to follow-up but represented aged 5.5 years with lymphocytic interstitial pneumonitis (LIP) and CDC stage.1 She was not initially commenced on HAART but subsequently developed acute renal failure and renal biopsy confirmed HIVAN. Hemodialysis and HAART (Lopinavir/ritonavir, lamivudine and abacavir) were started at 6.5 years. <h3>Results</h3> Pre-transplantation screening showed an undetectable HIV-1 viral load and CD4 counts of 43% (=1990/mm³). She underwent living related renal transplantation from her 56-year old maternal grandmother (mismatch 1,1,1; donor and recipient both CMV negative and EBV positive). There was a historical B-cell positive cross-match, and she was therefore treated as a ‘high-risk’ transplant using induction therapy with basiliximab, tacrolimus, mycophenolate mofetil and steroids. Tacrolimus was started six weeks prior to transplantation in order to stabilise levels. HAART (Lopinavir/ritonavir, abacavir and lamivudine) was continued together with isoniazid, azithromycin, co-trimoxazole and fluconazole prophylaxis. Currently, she is 2 months post-transplant with excellent allograft function - plasma creatinine 41-48 µmol/l; estimated glomerular filtration rate 80-94 mls/min/1.73m². She has mild hypertension requiring two anti-hypertensive agents and low-grade albuminuria (25 mg/mmol). Therapeutic tacrolimus levels are achieved with once-daily tacrolimus given 5-days per week only. She has an undetectable HIV-1 viral load and CD4+ counts of 240/mm³. Protocol biopsy at 6 weeks shows mild chronic changes, no donor specific antibodies and normal transplant renal ultrasound. There have been no HIV-related complications. <h3>Conclusion</h3> This is the first reported case of successful renal transplantation in a child with HIVAN in the UK. Adult experience suggests higher risk of rejection and careful monitoring for long-term HIV-associated complications.3

Combining Qualitative and Quantitative Evidence to Determine Factors Leading to Late Presentation for Antiretroviral Therapy in Malawi

BackgroundTreatment seeking delays among people living with HIV have adverse consequences for outcome. Gender differences in treatment outcomes have been observed in sub-Saharan Africa.ObjectiveTo better understand antiretroviral treatment (ART) seeking behaviour in HIV-infected adults in rural Malawi.MethodsQualitative interviews with male and female participants in an ART cohort study at a treatment site in rural northern Malawi triangulated with analysis of baseline clinical and demographic data for 365 individuals attending sequentially for ART screening between January 2008 and September 2009.Results43% of the cohort presented with late stage HIV disease classified as WHO stage 3/4. Respondents reported that women's frequency of testing, health awareness and commitment to children led to earlier ART uptake and that men's commitment to wider social networks of influence, masculine ideals of strength, and success with sexual and marital partners led them to refuse treatment until they were sick. Quantitative analysis of the screening cohort provided supporting evidence for these expressed views. Overall, male gender (adjusted OR 2.3, 95% CI1.3–3.9) and never being married (adjusted OR 4.1, 95% CI1.5–11.5) were risk factors for late presentation, whereas having ≥3 dependent children was associated with earlier presentation (adjusted OR 0.31, 95% CI0.15–0.63),compared to those with no dependent children.ConclusionGender-specific barriers and facilitators operate throughout the whole process of seeking care. Further efforts to enrol men into care earlier should focus on the masculine characteristics that they value, and the risks to these of severe health decline. Our results emphasise the value of exploring as well as identifying behavioural correlates of late presentation.

Commentary: Probability of HIV transmission through anal intercourse

Anal intercourse remains the most common means of HIV transmission in most of the developed world. Homosexual men represent the largest group of new HIV infections in Australia, Western Europe and North America. The rate of HIV diagnosis in homosexual men is on the increase in these regions, and this most likely reflects a true increase in HIV incidence. Recently, it has become clear that homosexual men are also disproportionately affected by HIV in much of the developing world. A detailed understanding of the transmissibility of HIV through anal intercourse, and co-factors which influence risk, is fundamental to the formulation of effective HIV prevention policy for homosexual men, and is also important for the substantial minority of heterosexual people who also practice anal intercourse. A recent review of the per-contact probability of HIV transmission by vaginal intercourse included data from dozens of prospective studies. In contrast, there is a dearth of data on per-contact probability of HIV transmission by anal intercourse. In the review published in this issue of the IJE, Baggaley et al. were able to include only four studies, including only a single prospective cohort. They were unable to find a single published estimate of the per-contact probability of HIV transmission by insertive anal intercourse. Baggaley et al. report a summary per-contact probability of transmission through receptive anal intercourse of 1.4%. This accords precisely with the probability calculated in an Australian study published in early 2010. In that study, the authors also concluded that the per-contact probability of transmission was lower (0.65%) when withdrawal prior to ejaculation occurred. The study also provided the first estimate of per-contact probability of HIV transmission via insertive anal sex, of 0.11% when the insertive partner was circumcised and 0.62% when the insertive partner was uncircumcised. The summary estimate of probability of transmission by receptive anal intercourse of 1.4% is 18-fold higher than the estimated probability of male to female vaginal intercourse, and goes some way to explain why homosexual men have been so disproportionately affected by HIV in developed countries. What co-factors might influence HIV transmission by anal intercourse? For vaginal intercourse, HIV viral load in the index case is of fundamental importance. In people with earlyand late-stage HIV disease, both of which are associated with high HIV viral load, per-contact probability of transmission through vaginal intercourse has been estimated to be 7–9-fold higher than in the asymptomatic phase of HIV infection. In untreated African heterosexuals, the HIV transmission rate increased dramatically with increasing viral load from 0 in couples where the HIV positive partner had a viral load of less than 1500, to 23 per 100 person-years in those couples where the viral load was more than 50 000. As effective antiretroviral therapy generally reduces HIV viral load to undetectable levels, it has been hypothesized that widespread treatment of HIV within a population could have a central role in HIV prevention. The question of whether anti-retroviral therapy will reduce sexual transmission of HIV is being addressed directly by a randomized controlled trial of early vs standard anti-retroviral therapy of HIV-infected individuals in serodiscordant couples. The primary outcome in this study is the rate of HIV infection in the initially HIV-negative partner. Trial results, anticipated to be available in 2013, will shape our understanding of the role of HIV treatment in HIV prevention in heterosexuals. What do we know about the effect of viral load and anti-retroviral therapy on rates of HIV transmission by anal intercourse? The fact that the per-contact probability of transmission is close to 20-fold higher than for vaginal intercourse is a strong argument for not simply extrapolating data from heterosexual populations. The modelling data presented by Baggaley and others demonstrate that the Published by Oxford University Press on behalf of the International Epidemiological Association

CD57 expression by T cells in the female genital tract of HIV-zx1 infected women

Despite an influx of T cells to the cervix during HIV infection, genital T cells are not associated with control of HIV shedding. CD57 expression by T cells has been associated with enhanced migratory potential and CD57+ T cells have been shown to accumulate in tissues during the late stages of HIV disease. We investigated the impact of HIV-infection and clinical status on the expression of CD57 by T cells from the female genital tract in 13 HIV-infected and 5 uninfected women. We found that cervical and blood-derived T cells expressed similar frequencies of CD57. The frequency of CD57 expression by cervical or blood T cells was not associated with clinical status (CD4 counts). No impairment in IFN-γ production by CD57+ T cells from the genital tract was observed. We conclude that increased T cell senescence does not appear to be a hallmark of genital mucosal HIV-1 infection.

The relationship between genotypic sensitivity score and treatment outcomes in late stage HIV disease after supervised HAART

This study investigated the effect of resistance testing quantified through a genotypic sensitivity score (GSS) on virologic, immunologic, and clinical responses among patients with late stage HIV-1 disease receiving supervised highly active antiretroviral therapy (HAART). Newly admitted patients received drug resistance testing (n = 198) and then HAART supervised by residential health-care facilities nurses. After initiating a resistance testing-informed HAART regimen, patients were followed for HIV-1 RNA suppression (<50 copies/ml), mean change in CD4(+) T-cells, new AIDS defining category C opportunistic conditions and death. GSS was constructed using the HAART regimen prescribed after resistance testing and data derived from IAS-USA consensus mutations table with modification. Regressions with generalized estimating equations for robust estimation of standard errors and Cox proportional hazards regression estimated independent associations between GSS and treatment responses. After adjusting for adherence, initial log(10) HIV-1 RNA levels, and other covariates, patients with a GSS > or =3 had significantly greater HIV-1 RNA suppression (adjusted odds ratio (AOR) 2.32; 95% CI 1.14, 4.75). HIV-1 RNA levels were lower among patients with > or =95% adherence, but the effect of GSS on viral suppression was not modified by adherence. Self-rated health status, and baseline CD4(+) T-cell counts independently predicted HIV-1 RNA suppression. GSS did not predict mean change in CD4(+) cells/mm(3) (236 vs. 233, P = 0.92), occurrence of new AIDS defining category C conditions or death. These data support resistance testing-guided therapy as an independent predictive factor to improve virologic responses in treatment-experienced patients.