The clinical profiles and outcomes of HIV-negative cryptococcal meningitis patients in type II diabetes mellitus.

BACKGROUND: The clinical profiles and outcomes of cryptococcal meningitis have been shown to vary depending on the underlying condition. The aim of this study was to investigate clinical characteristics and outcomes in patients with and without type II diabetes mellitus. METHODS: A retrospective study was performed. Clinical data of HIV-negative cryptococcal meningitis patients with type II diabetes mellitus (n = 26) and without type II diabetes mellitus (n = 52) referring to the Jiangxi Chest Hospital between January 2012 to December 2018 were analyzed. The data were analyzed using chi square, none-parametric tests, and logistic regression. P-values < 0.05 were considered significant. RESULTS: In this study, cryptococcal meningitis patients suffering from type II diabetes mellitus had a higher mortality (23.08% vs. 7.69%; P = 0.055), and required longer hospitalization (59.58 vs. 42.88 days; P = 0.132). Moreover, cerebrospinal fluid examinations revealed that cryptococcal meningitis patients with type II diabetes mellitus had higher opening pressure (271.54 vs. 234.23 mmH2O; P = 0.125).The results of multivariate regression analysis revealed that cryptococcal meningitis patients with type II diabetes were more often presented with visual disorders (28.54% vs. 11.54%; [95% CI 0.056-0.705]; p = 0.012), and had higher cerebrospinal fluid protein levels (1027.62 ± 594.16 vs. 705.72 ± 373.88 mg/l; [95% CI 1.000-1.002]; p = 0.016). Among patients with type II diabetes mellitus, nausea and vomiting was more frequent at the initial visit in those died (100% vs. 50%; p = 0.027), and 66% of died type II diabetes mellitus patients were poorly controlled blood glucose level, compared with 30% in survival type II diabetes mellitus patients. CONCLUSION: This study suggests that cryptococcal meningitis patients with type II diabetes mellitus differ significantly from cryptococcal meningitis patients without type II diabetes mellitus with respect to clinical symptoms such as visual disorders and cerebrospinal fluid examination. The presence of nausea and vomiting among type II diabetes mellitus patients could have implication in mortality.

Changes in T-lymphocyte subsets and risk factors in human immunodeficiency virus-negative patients with active tuberculosis.

PURPOSE: Immune function imbalance is closely associated with the occurrence and development of infectious diseases. We studied the characteristics of changes in T-lymphocyte subsets and their risk factors in HIV-negative patients with active tuberculosis (ATB). METHODS: T-lymphocyte subsets in 275 HIV-negative ATB patients were quantitatively analyzed and compared with an Mycobacteriumtuberculosis-free control group. Single-factor and multifactor analyses of clinical and laboratory characteristics of patients were also conducted. RESULTS: In ATB patients, CD4 and CD8 T-cell counts decreased, and the levels were positively interrelated (r = 0.655, P < 0.0001). After 4 weeks of antituberculosis treatment, CD4 and CD8 T-cell counts increased significantly but remained lower than in the control group. CD4 and CD8 cell counts were negatively associated with the extent of lesions detected in the chest by computed tomography (all P < 0.05). Although not reflected in the CD4/CD8 ratio, CD4 and CD8 cell counts differed between drug-resistant TB patients and drug-susceptible TB patients (P = 0.030). The multivariate analysis showed prealbumin, alpha-1 globulin, body mass index, and platelet count were independent risk factors for decreased CD4 cell count (all P < 0.05), while age and platelet count were independent risk factors for decreased CD8 cell count (all P < 0.05). CONCLUSION: CD4 and CD8 T-cell counts showed the evident value in predicting ATB severity. An increase in the CD4/CD8 ratio may be a critical clue of drug resistance in ATB. Although the factors influencing CD4 and CD8 are not identical, our results indicated the importance of serum protein and platelets to ATB patients' immune function.

The prevalence of renal impairment in individuals seeking HIV testing in Urban Malawi.

BACKGROUND: Chronic kidney disease (CKD) poses a major health threat to people living in low- and middle-income countries, especially when it is combined with HIV, antiretroviral treatment (ART) or communicable and non-communicable diseases. Data about the prevalence of CKD and its association with other diseases is scarce, particularly in HIV-negative individuals. This study estimated the prevalence of CKD in individuals who were either HIV-positive (and ART-naïve) or HIV-negative in an urban Malawian population. METHODS: This cross-sectional study was conducted at a HIV Testing and Counselling Centre in Lilongwe, Malawi. Consecutive clients who were ≥18 years and consented to participate were enrolled over a 3-month period. Clients were screened for potential renal disease and other conditions. Their blood pressure was measured, urine examined via dipstick and albumin/creatinine ratio and blood drawn for creatinine, cystatin C and sero-markers for schistosomiasis. Estimated glomerular filtration (eGFR) rate was calculated using a cystatin C-based formula and classified according to the matching CKD stages by K/DOQI (The National Kidney Foundation Kidney Disease Outcome Quality Initiative). We performed a descriptive analysis and compared differences between HIV-positive (and ART naïve) and -negative participants. RESULTS: Out of 381 consecutive clients who were approached between January and March 2012, 366 consented and 363 (48% female; 32% HIV-positive) were included in the analysis. Reasons for exclusion were missing samples or previous use of ART. HIV-positive and negative clients did not differ significantly with regard to age, sex or medical history, but they did differ for BMI-21.3 (±3.4) vs. 24 (±5.1), respectively (p < 0.001). Participants also differed with regard to serum cystatin C levels, but not creatinine. Reduced kidney function (according to CKD stages 2-5) was significantly more frequent 15.5 vs. 3.6%, respectively (p < 0.001) among HIV-positive clients compared to the HIV-negative group. Differences in renal function were most pronounced in the eGFR range 60-89 ml/min/1.73 m2 accompanied by proteinuria with results as 11.2% vs. 1.2%, respectively for clients who were HIV-positive vs. HIV-negative (p = 0.001). CONCLUSIONS: Reduced glomerular filtration and/or proteinuria occurred in 15.5% of HIV-positive, and 3.6% of HIV-negative patients in this urban Malawian cohort. Since generalized renal monitoring is not feasible in Malawi or other resource-limited countries, strategies to identify patients at risk for higher stages of CKD and appropriate preventive measures are needed for both HIV-positive and HIV-negative patients.

Myasthenia gravis developing in an HIV-negative patient with Kaposi's sarcoma.

Myasthenia gravis is a disorder of neuromuscular transmission caused by autoimmune mechanisms. We reported a possible association between seropositive myasthenia gravis and Kaposi's sarcoma in a HIV-negative subject and the observed interactions between the treatment regimen for these two conditions. A 62-year-old man came to our attention for ocular myasthenia gravis. He suffered from a classic form of Kaposi's sarcoma since about 1 year. When myasthenic symptoms worsened, the patient was started on prednisone and azathioprine. The patient had a significant worsening of Kaposi's sarcoma, so prednisone and azathioprine were reduced and he was treated with vinblastine, with improvement both in dermatologic than in neurological symptomatology. We propose some considerations: the potential correlation between Kaposi's sarcoma and myasthenia gravis through immunological mechanism; myasthenia gravis as a paraneoplastic manifestation of Kaposi's sarcoma, and the role of an antitumoral agent as a treatment for both the conditions.

[Sexuality and risk for sexual transmission of HIV among serodiscordant couples in Ouagadougou, Burkina Faso]. / Sexualité et risque de transmission du VIH chez les couples sérodiscordants suivis à l'hôpital de jour du CHU de Ouagadougou (Burkina Faso).

This article is a contribution to improve the management of serodiscordant couples in Ouagadougou. The aim of the study was to explore sexuality and the risk for sexual transmission of HIV among serodiscordant couples followed-up in CHU-YO. The study consisted of a descriptive cross-sectional study conducted over 6 months, from 1 January 2010 to 30 June 2010. A total of 80 heterosexual serodiscordant couples participated. Women were infected with HIV in most cases (75%). The mean age was 37.5 years for HIV partners and 40 years for seronegatives. Men were significantly older than women (p = 0.01). The couples weremarried (83.7%) or cohabiting (16.3%). The average of serodiscordance duration was 4 years. Seventy-four couples (92.5%) engaged in sexual intercourses, mostly vaginal intercourses. Both partners were satisfied only in 9 couples (12.2%). Although most couples (97.5%) knew the use of condoms for HIV prevention, 59.5% did not use it consistently, particularly when women were the seropositive partners (p = 0.01). The lack of privacy (37.5%) and desire of childbearing (26.25%) were the main reasons for not consistently using condoms among couples. Sexual dysfunction was a concern with 97.5% of the couples. The decrease in libido was most common (37.2%). Sexual intercourses with an outside partner were reported in 20 couples (25%), mostly regarding men (p = 0.03). Specific management could improve the quality of sexual life for couples in the light of the difficulties they face and reduce the risk for HIV transmission to negative partners.

Test-retest stability of calibrated BOLD-fMRI in HIV- and HIV+ subjects.

Subject performance, scanner hardware, or biological factors can affect single session neuroimaging measures. Stability studies using calibrated blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) have been performed in health but not disease. We utilized calibrated BOLD-fMRI to determine the effects of HIV on neurovascular coupling. Six clinically stable HIV-infected patients (HIV+) and 10 seronegative controls (HIV-) were scanned at two separate sessions approximately 3 months apart. Both mild hypercapnia (5% CO(2)) exposure and a visual functional activation task were performed. Intraclass correlation coefficients (ICC) and inter-subject variance were determined for calibrated BOLD-fMRI measures (baseline cerebral blood flow (CBF), functional CBF, BOLD, and cerebral metabolic rate of oxygen consumption (CMRO(2)) changes) for HIV+ and HIV- subjects. The two groups did not differ in age, sex, or education. HIV+ subjects had lower mean baseline CBF (p<0.04, Cohen's d=-1.07) and functional BOLD responses (p<0.001, Cohen's d=-2.47) and a trend towards a decrease in mean functional CBF responses (p=0.07, Cohen's d=-0.92) despite similar mean functional CMRO(2) changes (p=0.71, Cohen's d=0.19). The stability of each calibrated BOLD-fMRI measure, as assessed by ICC, was significantly lower for HIV+ subjects. In addition, HIV+ participants had greater inter-subject variability for baseline CBF (p<0.02), functional BOLD (p<0.001), CBF (p<0.001), and CMRO(2) (p<0.002) responses. Our results demonstrate that calibrated BOLD-fMRI measures have excellent stability within healthy controls. In contrast, these values have greater variability in clinically stable HIV+ subjects and may reflect alterations in coupling between CBF and CMRO(2) with disease.

An Uncommon Concurrence of Cytomegalovirus Retinitis and Corneal Endotheliitis in an Immunocompromised HIV-Negative Patient.

Purpose: To describe a case of Cytomegalovirus (CMV) retinitis in both eyes complicated with unilateral corneal endotheliitis in an iatrogenic immunocompromised patient.Methods: A retrospective case report.Result: A 58-year-old male, on long-term immunosuppressive treatment for chronic glomerulonephritis and nephrotic syndrome. Ocular examination revealed bilateral vitritis and necrotizing retinitis and concurrent corneal endotheliitis with ocular hypertension in his left eye. The PCR result showed positivity for CMV infection by diagnostic aqueous aspiration. Vitritis/retinitis in both eyes resolved gradually after systemic valganciclovir use, and the endotheliitis in the left eye regressed after topical antiviral treatment. There was no recurrence of retinitis/endotheliitis with a maintenance dose of oral valganciclovir. Unfortunately, tractional macular hole developed in the left eye and complicated the visual outcome.Conclusion: CMV retinitis may occur in HIV-negative immunocompromised individuals, but CMV endotheliitis generally appears in the immunocompetent. It is a rare combination of CMV retinitis and endotheliitis in this patient.

Fertility of HIV-infected women: insights from Demographic and Health Surveys.

OBJECTIVE: To analyse the data from Demographic and Health Survey (DHS) linking HIV serological data and fertility, and to recommend new age-specific fertility rate (ASFR) ratios of HIV-positive women to HIV-negative women to be used in the WHO/UNAIDS HIV estimates. METHODS: The authors obtained ASFRs and ASFR ratios from HIV-infected women and HIV-uninfected women from 20 DHS surveys collected between 2003 and 2007. The authors then computed mean and median ASFR ratios, and performed general linear modelling to estimate the overall ASFR ratio for each age group, and finally performed an analysis to identify determinants to national ASFR ratio for women aged 15-19 years old. RESULTS: The overall ASFR ratio estimated by regression was highest among women aged 15-19 years old (ASFR ratio of 1.20), and decreased with age (ASFR ratio of 0.76, 0.71, 0.65, 0.59 and 0.53, respectively for every 5-year bracket of 20-44 years old). The mean and median of ASFR ratios among 20 countries were similar to the results above. The analysis suggested that country-specific proportion of sexually active women aged 15-19 years old could be a determinant of the ASFR ratio for this group. The higher proportion of sexually active women in this group suggested a lower ASFR ratio in young women. CONCLUSION: This study confirmed previous findings of a high ASFR ratio among women younger than 20 years old, and of decreasing ASFR ratios with age among those aged 20 years or older, based on nationally representative data from a large number of countries. The study updated the assumptions used in the annual WHO/UNAIDS HIV epidemic estimates. Countries should compute their own ASFR ratio of 15-19-year-old women accounting for the sexually active rate among young females.

Risk behaviors in volunteer blood donors who seroconverted for HIV, Abidjan, Côte d'Ivoire 1997 to 2005.

BACKGROUND: The residual risk of human immunodeficiency virus (HIV) transmission from blood products in the Abidjan National Blood Transfusion Center was estimated to be 1 in 5780 blood donations over the period 2002 through 2004. We aimed at describing risk behaviors in blood donors who seroconverted for HIV in Abidjan to improve the pre-blood donation selection. STUDY DESIGN AND METHODS: We investigated the behavioral profile of HIV seroconverters assessed before their HIV diagnosis, during the blood donation selection at the blood bank of Abidjan, and compared it to the profile documented after this HIV diagnosis, at enrollment in the PRIMO-CI cohort. Since 1997, enrollment in this cohort is offered to every blood donor whose delay since HIV seroconversion was 36 months or less. RESULTS: Among the 418 blood donors who seroconverted for HIV between 1997 and 2005, 241 were enrolled in the cohort. Median age was 28 years and 63% were men. The median time between the last HIV-negative test and the first positive test was 7 months. Since the last blood donation, 29% of donors reported unprotected sexual intercourse with multiple casual sexual partners, 55% unprotected sexual intercourse with one casual sexual partner, and 36% sharing of nail clippers. During the pre-blood donation questionnaire, 69% of HIV seroconverters had reported unprotected sexual intercourse since the last blood donation (vs. 89% reported after donation), and 7% had had multiple casual sexual partners (vs. 32%). CONCLUSION: Volunteer blood donors who seroconverted for HIV in Abidjan reported a high proportion of unprotected sexual intercourse with casual sexual partners.

Sterol metabolism modulates susceptibility to HIV-1 Infection.

BACKGROUND: 25-hydroxylase (CH25H) is an interferon-stimulated gene (ISG), which catalyzes the synthesis of 25-hydroxycholesterol (25HC). 25HC intervenes in metabolic and infectious processes and controls cholesterol homeostasis and influences viral entry into host cells. We verified whether natural resistance to HIV-1 infection in HIV-1-exposed seronegative (HESN) individuals is at least partially mediated by particularities in sterol biosynthesis. METHODS: Peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages (MDMs) isolated from 15 sexually exposed HESN and 15 healthy controls were in vitro HIV-1-infected and analyzed for: percentage of IFNα-producing plasmacytoid dendritic cells (pDCs); cholesterol signaling and inflammatory response RNA expression; resistance to HIV-1 infection. MDMs from five healthy controls were in vitro HIV-1-infected in the absence/presence of exogenously added 25HC. RESULTS: IFNα-producing pDCs were augmented in HESN compared with healthy controls both in unstimulated and in in vitro HIV-1-infected PBMCs (P < 0.001). An increased expression of CH25H and of a number of genes involved in cholesterol metabolism (ABCA1, ABCG1, CYP7B1, LXRα, OSBP, PPARγ, SCARB1) was observed as well; this, was associated with a reduced susceptibility to in-vitro HIV-1-infection of PBMCs and MDMs (P < 0.01). Notably, addition of 25HC to MDMs resulted in increased cholesterol efflux and augmented resistance to in-vitro HIV-1-infection. CONCLUSION: Results herein show that in HESN sterol metabolism might be particularly efficient. This could be related to the activation of the IFNα pathway and results into a reduced susceptibility to in-vitro HIV-1 infection. These results suggest a possible basis for therapeutic interventions to modulate HIV-1 infection.

Auditory, video head impulse test and vestibular evoked myogenic potentials findings in adults with human immunodeficiency virus.

OBJECTIVES: Even though there is an association between hearing loss and human immunodeficiency virus (HIV), particularly in low- and middle-income countries, further research is needed to investigate the nature of such hearing loss. Likewise, despite documented vestibular alterations in people with HIV, the true occurrence, presentation, and nature of these manifestations are yet to be established. Advances in technology for vestibular testing has allowed for objective site-of-lesion tests such as the video head impulse test (vHIT), cervical vestibular evoked myogenic potentials (cVEMPs) and ocular vestibular evoked myogenic potential (oVEMPs). The current study aimed to compare and describe auditory, vHIT, cVEMPs and oVEMPs findings in adults with and without HIV. METHODS: The current study included an HIV positive group (n = 30) and an HIV negative group (n = 30) who underwent an auditory assessment (tympanometry and pure tone audiometry) and objective vestibular assessments. RESULTS: The occurrence of hearing loss was 53.3% in the HIV positive group compared to 33.3% in the HIV negative group. A higher occurrence of vestibular involvement was documented in the HIV positive group (73.3%) compared to 13.3% in the HIV negative group. CONCLUSION: Auditory assessment and objective measures of vestibular end-organ function (vHIT and VEMPs) can be useful to detect sub-clinical alterations. The equipment is mobile and can be performed in any health care setting such as infectious disease clinics for surveillance and monitoring purposes.

Frequent expression of activation-induced cytidine deaminase in diffuse large B-cell lymphoma tissues from persons living with HIV.

OBJECTIVE: The increased risk for persons living with HIV to develop diffuse large B-cell lymphoma (DLBCL) even in the post-antiretroviral therapy eras suggests a role beyond immunosuppression in lymphoma development. However, the mechanisms leading to lymphoma in the HIV setting are not fully understood. HIV is known to induce activation-induced cytidine deaminase (AID) levels in nonneoplastic B cells in vitro and chronic AID expression may play an important role in lymphomagenesis. Although AID expression is observed in B-cell lymphoma, studies in HIV-associated DLBCL are limited. DESIGN: In this study, we conducted a retrospective review of DLBCL tissues from patients with and without HIV infection to compare expression of AID and B-cell receptors potentially involved in HIV and B-cell interaction. METHODS: We evaluated DLBCL formalin-fixed paraffin-embedded tissues from 72 HIV-seropositive and 58 HIV-seronegative patients for AID, DC-SIGN, and CD40 protein expression. BCL2 and MYC, two well established prognostically significant oncoproteins in DLBCL, were also assessed at the protein and mRNA levels. Subset analysis was performed according to DLBCL subtype and EBV status. RESULTS: Of note, AID expression was more frequent in HIV-associated DLBCL compared with non-HIV-associated DLBCL regardless of cell-of-origin subtype, and also displayed significantly less BCL2 expression. Despite no direct correlation with AID expression, the HIV-DLBCL tissues also exhibited high levels of the DC-SIGN receptor. CONCLUSION: Collectively, these findings support a potential role for AID in the pathogenesis of HIV-associated lymphomas and suggest the need of further investigations into the involvement of the DC-SIGN receptor-signaling pathway.

Human immunodeficiency virus type 1 in the central nervous system leads to decreased dopamine in different regions of postmortem human brains.

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after infection and becomes localized in varying concentrations in different brain regions, the most vulnerable is the basal ganglia (BG). It is hypothesized that HIV-1-mediated neuropathogenesis involves degeneration of dopaminergic neurons in the substantia nigra and the loss of dopaminergic terminals in the BG, leading to deficits in the central dopaminergic activity, resulting in progressive impairment of neurocognitive and motor functions. In the era of highly active antiretroviral therapy (HAART), although the incidence of HIV-associated dementia (HAD) has decreased, the neurocognitive and neuropsychological deficits continue to persist after HAART. In this study, We investigated the impact of HIV-1 on dopaminergic activity with respect to concentrations of dopamine (DA) and homovanillic acid (HVA) in different regions of postmortem human brains of HIV-1-negative and HIV-1+ individuals and their relationship to neurocognitive impairment. We found that in HIV-1+ as well as HIV-negative cases, dopamine and HVA concentrations in ranged widely in different brain regions. In HIV-negative brain regions, the highest concentration of DA was found in putamen, caudate, substantia nigra, and the basal ganglia. In HIV-1+ cases, there was a significant decrease in DA levels in caudate nucleus, putamen, globus pallidus, and substantia nigra compared to that in HIV-negative cases. In HIV-1+ cases, a strong correlation was found between DA levels in substantia nigra and other brain regions. Concentration of HVA in HIV-negative cases was also highest in the regions containing high dopamine levels. However, no significant decrease in regional HVA levels was found in HIV-1+ cases. HIV-1 RNA load (nondetectable [ND] to log10 6.9 copies/g tissue) also ranged widely in the same brain regions of HIV-1+ cases. Interestingly, the brain regions having the highest HIV-1 RNA had the maximum decrease in DA levels. Age, gender, ethnicity, and postmortem interval were not correlated with decrease in DA levels. Profile of DA, HVA, and HIV-1 RNA levels in the brain regions of HIV-1+ individuals treated with HAART was similar to those not treated with HAART. A majority of HIV-1+ individuals had variable degrees of neurocognitive impairments, but no specific relationship was found between the regional DA content and severity of neurocognitive deficits. These findings suggest widespread deficits in dopamine in different brain regions of HIV-1-infected cases, and that these deficits may be the results of HIV-1-induced neurodegeneration in the subcortical regions of human brain.

A prospective study of risk factors for herpes simplex virus type 2 acquisition among high-risk HIV-1 seronegative women in Kenya.

OBJECTIVES: Several studies have demonstrated an association between herpes simplex virus type 2 (HSV-2) and HIV-1, but available data on risk factors for HSV-2 acquisition are limited. The objective of this analysis was to determine the incidence and risk factors for HSV-2 acquisition among HIV-1-seronegative female sex workers in Kenya. METHODS: Between February 1993 and December 2006, HIV-1-seronegative women attending a municipal sexually transmitted infection (STI) clinic were invited to enroll in a prospective cohort study. Screening for HIV-1 and STIs were done at monthly follow-up visits. Archived blood samples were tested for HSV-2. RESULTS: Of 1527 HIV-1-seronegative women enrolled, 302 (20%) were HSV-2 seronegative at baseline of whom 297 had at least one follow-up visit. HSV-2 incidence was high (23 cases/100 person-years; 115 cases). In multivariate analysis, HSV-2 was significantly associated with more recent entry into sex work, workplace and higher number of sex partners per week. Condom use was protective, although this was statistically significant only for the intermediate strata (25-75% condom use; HR 0.43; p = 0.05). There were statistical trends for bacterial vaginosis to increase HSV-2 risk (HR 1.56; p = 0.07) and for oral contraceptive use to decrease risk (HR 0.50; p = 0.08). The 23% annual HSV-2 incidence in this study is among the highest reported anywhere in the world. CONCLUSIONS: Women were at increased risk if they had recently entered sex work, had a higher number of sex partners or worked in bars. HSV-2 risk reduction interventions are urgently needed among high-risk African women.

Anal squamous intraepithelial lesions among HIV positive and HIV negative men who have sex with men in Thailand.

OBJECTIVES: To evaluate the prevalence and risk factors of anal squamous intraepithelial lesions (ASIL), the putative anal cancer precursor, in Asian HIV positive and HIV negative men who have sex with men (MSM). METHODS: Men who underwent anal Pap smear reported clinical, sociodemographic and behavioural information collected through questionnaire and interview between January 2007 and April 2008. Chi(2) and logistic regression were used to evaluate ASIL prevalence and risk factors among HIV positive and HIV negative MSM. RESULTS: Of the 174 MSM (mean age 32.1 years), 118 (67.8%) were HIV positive. Overall, 27% had abnormal anal cytology: 13.2% had atypical squamous cells of undetermined significance (ASC-US), 11.5% had low-grade squamous intraepithelial lesion (LSIL) and 2.3% had high-grade squamous intraepithelial lesion (HSIL). Prevalence of ASIL was higher among HIV positive than HIV negative MSM (33.9% vs 12.5%; p = 0.003). Among HIV positive MSM, 16.1% had ASC-US, 14.4% had LSIL and 3.4% had HSIL and 7.1%, 5.4% and 0% in HIV negative MSM, respectively. Anal condyloma was detected in 22% of HIV positive and 16.1% (9/56) of HIV negative MSM (p = 0.5). In HIV positive MSM, anal condyloma (OR 3.42, 95% CI 1.29 to 9.04; p = 0.01) was a significant risk factor for ASIL. Highly active antiretroviral therapy use and CD4+ T cell count were not associated with ASIL. CONCLUSIONS: One-third of HIV positive and 12.5% of HIV negative MSM had ASIL. Thus, as greater numbers of HIV positive MSM live longer due to increasing access to HAART worldwide, effective strategies to screen and manage anal precancerous lesions are needed.

Effect of saquinavir/ritonavir (1000/100 mg bid) on the pharmacokinetics of methadone in opiate-dependent HIV-negative patients on stable methadone maintenance therapy.

This study was performed to determine the effect of two protease inhibitors, saquinavir (SQV, oral 1000 mg bid) boosted by ritonavir (RTV, oral 100 mg bid), on pharmacokinetics (PK) of methadone in opiate-dependent HIV-negative patients on stable methadone maintenance therapy. This was a two-center, open-label, one-sequence cross-over, multiple-dose study in 13 HIV-negative patients who were on stable methadone therapy (oral, 60-120 mg qd). All patients continued methadone treatment on days 2-15. All patients received SQV/RTV in combination with methadone from days 2-15. PK of methadone was assessed on day 1 (alone) and on day 15 when methadone treatment was combined with SQV/RTV at steady state. Twelve patients completed the study. Median age, body weight and height were 50 years (range: 24-54 years), 80 kg (range: 57-97 kg) and 174 cm (range: 163-189 cm), respectively. All patients were Caucasian, and 11 were smokers. Median methadone dose was 85 mg qd. Geometric mean area under curve of the plasma concentration-time curve over 24 hour dosing interval (AUC(0-24 hour)) ratio of methadone with and without SQV/RTV was 0.81% (90% confidence interval: 71-91%). There was no significant plasma protein-binding displacement of methadone by SQV/RTV. The combination of SQV/RTV and methadone was well tolerated. There were no clinically significant adverse events or significant changes in laboratory parameters, electrocardiograms or vital signs. The 19% decrease in R-methadone AUC(0-24 hour) in the presence of SQV/RTV was not clinically relevant. There appears to be no need for methadone dose adjustment when methadone (60-120 mg qd) and SQV/RTV (1000/100 mg bid) are coadministered.

Whole gastrointestinal transit time is associated with clinical severity and nutritional status of HIV-infected children.

BACKGROUND: Malnutrition and malabsorption are common consequences in pediatric human immunodeficiency virus (HIV) infection. The gastrointestinal tract is a major site affected by HIV Rapid gastrointestinal transit time may contribute to malabsorption. OBJECTIVE: To determine whether the whole gastrointestinal transit time (WGTT) correlates with disease stages or degrees of malnutrition in HIV-infected children. MATERIAL AND METHOD: Forty HIV-seropositive children, at various stages of disease, and thirty seronegative age-matched controls, aged between 1 mo and 3 yr, were enrolled in the present study. The body weight, length, or height and the WGTT were assessed Then the WGTT of children in different stages of HIV disease and in different degrees of malnutrition were compared with those of the control group. RESULTS: The mean ages were 15.5 and 14.3 mo in HIV-infected and control groups respectively. A greater degree of malnutrition was found in HIV-infected children with more advances HIV clinical symptoms. Compared to controls, WGTT was most rapid in severely symptomatic acquired immunodeficiency syndrome (AIDS) patients (Category C) (14.32 +/- 3.88 versus 7.22 +/- 3.17 h; p < 0.01) but not in asymptomatic, mildly and moderately symptomatic children. Accelerated WGTT in HIV-infected children was also significantly associated with a higher degree of malnutrition. CONCLUSION: Malnutrition is clearly related to the progression ofHIV disease. Accelerated WGTT is associated with HIV seropositivity, severe clinical symptoms, and higher degrees of malnutrition.

Placental Structure in Preterm Birth Among HIV-Positive Versus HIV-Negative Women in Kenya.

BACKGROUND: Preterm birth (PTB) is a major cause of infant morbidity and mortality in developing countries. Recent data suggest that in addition to Human Immunodeficiency Virus (HIV) infection, use of antiretroviral therapy (ART) increases the risk of PTB. As the mechanisms remain unexplored, we conducted this study to determine whether HIV and ART were associated with placental changes that could contribute to PTB. SETTING: We collected and evaluated placentas from 38 HIV-positive women on ART and 43 HIV-negative women who had preterm deliveries in Nairobi, Kenya. METHODS: Anatomical features of the placentas were examined at gross and microscopic levels. Cases were matched for gestational age and compared by the investigators who were blinded to maternal HIV serostatus. RESULTS: Among preterm placentas, HIV infection was significantly associated with thrombosis (P = 0.001), infarction (P = 0.032), anomalies in cord insertion (P = 0.02), gross evidence of membrane infection (P = 0.043), and reduced placental thickness (P = 0.010). Overall, preterm placentas in both groups were associated with immature villi, syncytial knotting, villitis, and deciduitis. Features of HIV-positive versus HIV-negative placentas included significant fibrinoid deposition with villus degeneration, syncytiotrophoblast delamination, red blood cell adhesion, hypervascularity, and reduction in both surface area and perimeter of the terminal villi. CONCLUSIONS: These results imply that HIV infection and/or ART are associated with morphological changes in preterm placentas that contribute to delivery before 37 weeks. Hypervascularity suggests that the observed pathologies may be attributable, in part, to hypoxia. Further research to explore potential mechanisms will help elucidate the pathways that are involved perhaps pointing to interventions for decreasing the risk of prematurity among HIV-positive women.

Association between fertility and HIV status: what implications for HIV estimates?

BACKGROUND: Most estimates of HIV prevalence have been based on sentinel surveillance of pregnant women which may either under-estimate or over-estimate the actual prevalence in adult female population. One situation which can lead to either an underestimate or an overestimate of the actual HIV prevalence is where there is a significant difference in fertility rates between HIV-positive and HIV-negative women. Our aim was to compare the fertility rates of HIV-infected and HIV-uninfected women in Cameroon in order to make recommendations on the appropriate adjustments when using antenatal sentinel data to estimate HIV prevalence. METHODS: Cross-sectional, population-based study using data from 4493 sexually active women aged 15 to 49 years who participated in the 2004 Cameroon Demographic and Health Survey. RESULTS: In the rural area, the age-specific fertility rates in both HIV positive and HIV negative women increased from 15-19 years age bracket to a maximum at 20-24 years and then decreased monotonically till 35-49 years. Similar trends were observed in the urban area. The overall fertility rate for HIV positive women was 118.7 births per 1000 woman-years (95% Confidence Interval [CI] 98.4 to 142.0) compared to 171.3 births per 1000 woman-years (95% CI 164.5 to 178.2) for HIV negative women. The ratio of the fertility rate in HIV positive women to the fertility rate of HIV negative women (called the relative inclusion ratio) was 0.69 (95% CI 0.62 to 0.75). CONCLUSION: Fertility rates are lower in HIV-positive than HIV-negative women in Cameroon. The findings of this study support the use of summary RIR for the adjustment of HIV prevalence (among adult female population) obtained from sentinel surveillance in antenatal clinics.

Pneumocystis jirovecii pneumonia (PCP) PCR-negative conversion predicts prognosis of HIV-negative patients with PCP and acute respiratory failure.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is often fatal in human immunodeficiency (HIV)-negative patients and typically presents with respiratory insufficiency. Predicting treatment failure is challenging. This study aimed to identify prognostic factors and examine PCP polymerase chain reaction (PCR)-negative conversion in non-HIV PCP patients with respiratory failure. METHOD: We retrospectively enrolled 81 non-HIV patients diagnosed with and treated for PCP with respiratory failure in the intensive care unit at a tertiary hospital over a 3-year period. PCP was diagnosed via nested PCR-mediated detection of Pneumocystis jirovecii in induced sputum samples, endotracheal aspirates, and bronchoalveolar lavage fluids. PCP PCR was performed weekly to check for negative conversion. RESULTS: The overall survival rate was 35.8%. Seventy-four patients (91.3%) required mechanical ventilation, and 6 (7.4%) required high-flow nasal oxygen treatment. The PCP PCR-negative conversion rate was 70.5% (survivors, 97%; non-survivors, 63.5%); the median time to conversion was 10 (7.0-14.0) days. On univariate analysis, the APACHE II score (p < 0.001), renal failure requiring renal replacement therapy (p = 0.04), PCP PCR-negative conversion (p = 0.003), and the PaO2/FiO2 ratio (first 24 hours) (p < 0.001) significantly correlated with mortality. On multivariate analysis, PCP PCR-negative conversion (hazard ratio, 0.433; 95% confidence interval, 0.203-0.928; p = 0.031) and the PaO2/FiO2 ratio (first 24 hours) (hazard ratio, 0.988; 95% confidence interval, 0.983-0.993; p < 0.001) independently predicted prognosis. CONCLUSIONS: Determination of PCP PCR-negative conversion and PaO2/FiO2 ratios may help physicians predict treatment failure and mortality in non-HIV PCP patients with respiratory failure.