Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis

Purpose

To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula) compared with age-matched HIV-negative controls.

Methods

Cohort of patients with known HIV under CART (combination Antiretroviral Therapy) treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT) to assess retinal layers and retinal thickness.

Results

Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative) were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior), the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308–6,872 cones/mm²). A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative) was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea). We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer) was also significantly thickened in all the different locations scanned compared with HIV-negative controls.

Conclusion

Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis.     

Shorter Telomere Length - A Potential Susceptibility Factor for HIV-Associated Neurocognitive Impairments in South African Woman

The neuropathogenesis of the human immunodeficiency virus (HIV) may manifest as various neurocognitive impairments (NCI). HIV-positive individuals also have significantly shorter telomere length (TL) in peripheral blood mononuclear cells (PBMCs) and CD8+ T cells compared to HIV-negative individuals. Additionally, reduced TL has been found to be associated with chronic psychological stress. This study focused on the effects of HIV-infection and chronic stress associated with childhood trauma on telomere length, and investigated whether leukocyte TL (LTL), in particular, represents a risk factor for NCI. Eighty-three HIV-positive and 45 HIV-negative women were assessed for childhood trauma and were subjected to detailed neurocognitive testing. Blood from each participant was used to extract Deoxyribonucleic acid (DNA). Relative LTL were determined by performing real time quantitative PCR reactions as described by Cawthon et al. (2002). As expected, relative LTL in the HIV-positive individuals was significantly shorter than that of HIV-negative individuals (F = 51.56, p = <0.01). Notably, a significant positive correlation was evident between relative LTL and learning performance in the HIV-positive group. In addition, a significant negative correlation was observed between relative LTL and verbal fluency, but this association was only evident in HIV-positive individuals who had experienced trauma. Our results suggest that reduced LTL is associated with worse learning performance in HIV-positive individuals, indicating that TL could act as a susceptibility factor in increasing neurocognitive decline in HIV-infected individuals.     

Antisperm antibodies in human immunodeficiency virus infection: effects on fertilization and embryonic development

Sera from human immunodeficiency virus (HIV)-infected males (n = 10) and females (n = 5) were analyzed for the presence of antisperm antibodies reacting against sperm-specific antigens. Of the HIV-positive males tested, sera of 40% were positive for human sperm extract (HSE), 70% for protamine, and 70% for fertilization antigen (FA-1) for at least one class of antibodies, compared to sera from HIV-negative males. Of the HIV-positive females tested, sera of 40% were positive for HSE, 30% for protamine, and 30% for FA-1 compared to sera from HIV-negative females. The majority of the sperm antigen-reactive antibodies belonged to the IgG class. The reactions observed with FA-1 were weaker than those with other antigens. Ninety percent of HIV-positive male sera and 80% of the HIV-negative female sera were found to contain immune complexes, 20% of which showed the presence of FA-1. HIV-positive male or female sera did not bind to any specific protein on the Western blot of HSE. The minimal amount of free anti-FA-1 antibodies present in sera did not bind to live sperm in the sperm immobilization technique, sperm agglutination technique, or immunobead binding technique and thus were incapable of affecting human sperm penetration of zona-free hamster ova (SPA). Nor did HIV-positive sera induce any apparent abnormality in the development of 2-cell embryos to blastocysts in vitro in murine bioassay. In conclusion, these results indicate that HIV-infected patients have sperm-specific antibodies in their sera that do not adversely affect SPA and murine embryo bioassay. There was a high incidence of immune complex formation after HIV infection. These data will provide the basis for exploring further the role of sperm antigens in altering the immunoregulatory mechanisms after HIV infection.     

Time to Complete Wound Healing in HIV-Positive and HIV-Negative Men following Medical Male Circumcision in Kisumu,Kenya: A Prospective Cohort Study

Background

While voluntary medical male circumcision (VMMC) has been shown to be protective against HIV-acquisition, the procedure may place men and their partners at risk of HIV infection in the period following circumcision if sex is resumed before the wound is healed. This prospective cohort study evaluates post-circumcision wound healing to determine whether the 42-day post-circumcision abstinence period, recommended by the World Health Organization and adopted by VMMC programs, is optimal.

Methods and Findings

Men were circumcised by forceps-guided method and their post-circumcision wounds examined weekly for seven weeks and at 12 weeks. Time to complete healing was recorded in completed weeks since circumcision, and its associations with baseline covariates were assessed by Kaplan-Meier methods and Cox Proportional Hazard Models. A total of 215 HIV-negative and 108 HIV-positive men aged 18–35 years (median 26, IQR 23–30) were enrolled. 97.1% of scheduled follow-up visits were completed. At week 4, 59.3% of HIV-positive men and 70.4% of age-matched HIV-negative men were healed. At week 6, these percentages rose to 93.4% in HIV-positive men and 92.6% in age-matched HIV-negative men. There was no difference in the hazard of healing between 108 HIV-positive and 108 age-matched HIV-negative men (HR 0.91 95% CI 0.70–1.20). Early post-operative infection was associated with delayed healing in both HIV-positive and HIV-negative men (HR 0.48 95% CI 0.23–1.00).

Conclusions

Our results indicate that the WHO recommendation for 42-days post-circumcision sexual abstinence should be maintained for both HIV-positive and HIV-negative men. It is important to stress condom use upon resumption of sex in all men undergoing circumcision.     

Plasma Lipidomic Profiling of Treated HIV-Positive Individuals and the Implications for Cardiovascular Risk Prediction

Background

The increased risk of coronary artery disease in human immunodeficiency virus (HIV) positive patients is collectively contributed to by the human immunodeficiency virus and antiretroviral-associated dyslipidaemia. In this study, we investigate the characterisation of the plasma lipid profiles of treated HIV patients and the relationship of 316 plasma lipid species across multiple lipid classes with the risk of future cardiovascular events in HIV- positive patients.

Methods

In a retrospective case-control study, we analysed plasma lipid profiles of 113 subjects. Cases (n = 23) were HIV-positive individuals with a stored blood sample available 12 months prior to their diagnosis of coronary artery disease (CAD). They were age and sex matched to HIV-positive individuals without a diagnosis of CAD (n = 45) and with healthy HIV-negative volunteers (n = 45).

Results

Association of plasma lipid species and classes with HIV infection and cardiovascular risk in HIV were determined. In multiple logistic regression, we identified 83 lipids species and 7 lipid classes significantly associated with HIV infection and a further identified 74 lipid species and 8 lipid classes significantly associated with future cardiovascular events in HIV-positive subjects. Risk prediction models incorporating lipid species attained an area under the receiver operator characteristic curve (AUC) of 0.78 (0.775, 0.785)) and outperformed all other tested markers and risk scores in the identification of HIV-positive subjects with increased risk of cardiovascular events.

Conclusions

Our results demonstrate that HIV-positive patients have significant differences in their plasma lipid profiles compared with healthy HIV-negative controls and that numerous lipid species were significantly associated with elevated cardiovascular risk. This suggests a potential novel application for plasma lipids in cardiovascular risk screening of HIV-positive patients.     

Using the number of koilocytes to predict HIV serostatus in women with HPV-associated SIL

OBJECTIVE: To investigate the relationship between specific cytopathologic changes, koilocyte counts and human papillomavirus (HPV) types in HIV-positive and -negative women. STUDY DESIGN: A cohort of 459 women (266 HIV+ and 193 HIV-), were examined in a multicentric study (Early Diagnosis of Neoplasia in AIDS) involving 14 gynecologic centers. Altogether, 97 women had cervical smears consistent with squamous intraepithelial lesions (SIL). Koilocytes were found in 60/97 SIL slides, subjected to quantitative counting in 30 predetermined fields. HPV genotype was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. RESULTS: SIL lesions were four times more frequent (29%) in HIV-positive women than in HIV-negative women (10%) (odds ratio = 3.80). HPV DNA was equally frequent in both groups. There was a strong association between the number of koilocytes and HIV serostatus in both high grade and low grade SIL diagnoses. The presence of eight or more koilocytes had a specificity of 93% and sensitivity of 76% toward the diagnosis of HIV-positive status. No HIV-negative woman had a count > 8 koilocytes. No association was shown between koilocyte count and HPV genotype. CONCLUSION: An elevated number of koilocytes could suggest the possibility of HIV infection. Pap smear examination might give the first clue to HIV positivity in otherwise-unsuspected cases.     

隐球菌性脑膜炎治疗的更新

隐球菌性脑膜炎(cryptococcal meningitis,CM)是一种由新型隐球菌和格特隐球菌引起的机会性真菌感染性疾病。尽管近些年来,随着CM诊断方法与治疗手段的重大进展,患者整体病死率明显下降,但其发病率在世界范围内仍呈升高趋势,在我国尤为明显。虽然CM常发生在有免疫缺陷的人群如HIV患者,但HIV阴性的人群患病率却逐年升高,且二者的治疗方案不尽相同。本文总结了国内外关于HIV阳性与HIV阴性隐球菌性脑膜炎患者治疗的新进展,旨在对HIV阳性和HIV阴性隐球菌性脑膜炎患者的治疗提供依据。     

Outcomes and Diagnostic Processes in Outpatients with Presumptive Tuberculosis in Zomba District,Malawi

Background

In Malawi, outpatients who have presumptive tuberculosis (TB), i.e. fever, night sweats, weight loss and/or any-duration cough (HIV-infected) or cough of at least 2 weeks (HIV-uninfected), are registered in chronic cough registers. They should receive a diagnostic work-up with first-step provider-initiated HIV testing and sputum testing which includes XpertMTB/RIF, following a national algorithm introduced in 2012.

Methods

An operational study, in which we prospectively studied 6-month outcomes of adult outpatients who were registered in chronic cough registers in Zomba Central Hospital and Matawale peri-urban Health Center, between February and September 2013. We recorded implementation of the diagnostic protocol and outcomes at 6 months from registration.

Results

Of 348 patients enrolled, 165(47%) were male, median age was 40 years, 72(21%) had previous TB. At registration 154(44%) were known HIV-positive, 34(10%) HIV-negative (26 unconfirmed) and 160(46%) had unknown HIV status; 104(56%) patients with unknown/unconfirmed HIV status underwent HIV testing. At 6 months 191(55%) were HIV-positive, 87(25%) HIV-negative (26 unconfirmed) and 70(20%) still had unknown HIV status. Higher age and registration in Matawale were independently associated with remaining unknown HIV status after 6 months. 62% of patients had sputum tested, including XpertMTB/RIF, according to the algorithm. TB was diagnosed in 54(15%) patients. This was based on XpertMTB/RIF results in 8(15%) diagnosed cases. In 26(48%) TB was diagnosed on clinical grounds. Coverage of ART in HIV-positive patients was 89%. At 6 months, 236(68%) were asymptomatic, 48(14%) symptomatic, 25(7%) had been lost-to-follow-up and 39(11%) had died. Mortality among those HIV-positive, HIV-negative and with unknown HIV-status was 15%, 2% and 10%, respectively. Male gender, being HIV-positive-not-on-ART and not receiving antibiotics were independent risk factors for mortality.

Conclusion

HIV prevalence among patients with presumptive TB was high (55%). One quarter was not HIV tested and mortality in this group was substantial (10%). The impact of XpertMTB/RIF on TB diagnosis was limited.     

Identification of a New Microsporidian Parasite Related to Vittaforma corneae in HIV-Positive and HIV-Negative Patients from Portugal

ABSTRACT. Fecal samples from 22 HIV-positive and 3 HIV-negative patients from Portugal with symptomatic diarrhea were diagnosed positive for microsporidia by microscopy, with most parasites detected significantly bigger than Enterocytozoon bieneusi and Encephalitozoon spp. Sequence characterization of the small subunit (SSU) rRNA gene identified a microsporidian parasite with 96% homology to two published Vittaforma corneae sequences. Phylogenetic analysis confirmed the genetic relatedness of this new microsporidian parasite to Vittaforma corneae as well as Cystosporogenes operophterae. Results of the study demonstrate the presence of a new human-pathogenic microsporidian species, which is responsible for significant number of infections in HIV-positive and HIV-negative patients in Portugal.     

Polymerase chain reaction for Mycobacterium tuberculosis complex DNA. Use on negative archival Ziehl-Neelsen cytologic samples

OBJECTIVE: To evaluate the usefulness of a nested polymerase chain reaction (PCR) for Mycobacterium tuberculosis complex on routinely stained cytologic samples from patients with extrapulmonary tuberculosis. STUDY DESIGN: Nested PCR for the detection of a fragment of the IS6110 insertion sequence of M tuberculosis complex was applied to Ziehl-Neelsen-negative archival cytologic slides of serous effusions (pleural [n = 7], peritoneal [n = 1] and pericardial [n = 1]) and a lymph node fine needle aspirate (n = 1) from nine human immunodeficiency virus (HIV)-positive patients with autopsy-proven active extrapulmonary tuberculosis. Malignant effusions and aspirates from nine HIV-positive patients with non-Hodgkin's lymphoma and pleural effusions from seven HIV-negative patients with heart failure were used as controls. DNA was extracted after removing the coverslip and gently scraping the cytologic sample from the slides. RESULTS: In all cases, enough DNA was obtained for PCR without any significant loss of integrity, as demonstrated by PCR positive for HLA-Dq. PCR for M tuberculosis was positive in 8 of the 10 samples (80%) from patients with tuberculosis but also in three samples (30%) from HIV-positive patients in the control group. None of the samples from the HIV-negative patients was positive. CONCLUSION: PCR for M tuberculosis can be reliably performed on archival cytologic slides from extrapulmonary samples, but although it is highly sensitive, it may lead to positive results in immunocompromised patients without any sign of active tubercular disease.     

Presence of IgG Anti-gp160/120 Antibodies Confers Higher HIV Capture Capacity to Erythrocytes from HIV-Positive Individuals

Background

HIV binding has been demonstrated in erythrocytes from HIV-positive and HIV-negative individuals. However, the presence of immunoglobulins G anti-HIV (IgG anti-HIV) in erythrocytes from HIV-positive individuals is still to be elucidated. Moreover, the capacity of erythrocytes from HIV-positive individuals to capture an additional amount of HIV has not been studied. Indeed, it is unknown if HIV binding to erythrocytes in HIV-positive persons could have consequences on the cell-free infectious virus available.

Methodology/Principal Findings

IgGs anti-HIV associated to erythrocytes were found in 77.3% (58/75) of the HIV-positive individuals studied and the IgGs anti-gp160 and anti-p24 were the most frequently found. We found a positive association between detectable plasma viral load (pVL) and presence of IgGs anti-HIV associated to erythrocyte (p<0.005), though the anti-p24/160 were present with or without detectable pVL. The HIV capture capacity was higher in erythrocytes from HIV-positive than HIV-negative individuals (p<0.0001). Furthermore, among the HIV-positive individuals the higher viral capture capacity was associated with the presence of anti-gp160/gp120 on erythrocytes. Moreover, the viral capture by erythrocytes was independent of pVL (rho = 0.022, p = 0.8817). Additionally, reduction of cell-free infectious virus and available viral load was observed in the presence of erythrocytes from HIV-positive individuals.

Conclusions/Significance

Results suggest that in HIV-positive individuals, erythrocytes are capable of capturing high amounts of HIV by the presence of IgGs anti-gp160/120 on their membranes and this may produce a reduction in the available free virus. Finally, the current measurement of pVL would underestimate the real viral quantity due to the HIV binding through specific antibodies to erythrocytes.     

Infant feeding practices at routine PMTCT sites, South Africa: results of a prospective observational study amongst HIV exposed and unexposed infants - birth to 9 months

Background

We sought to investigate infant feeding practices amongst HIV-positive and -negative mothers (0-9 months postpartum) and describe the association between infant feeding practices and HIV-free survival.

Methods

Infant feeding data from a prospective observational cohort study conducted at three (of 18) purposively-selected routine South African PMTCT sites, 2002-2003, were analysed. Infant feeding data (previous 4 days) were gathered during home visits at 3, 5, 7, 9, 12, 16, 20, 24, 28, 32 and 36 weeks postpartum. Four feeding groups were of interest, namely exclusive breastfeeding, mixed breastfeeding, exclusive formula feeding and mixed formula feeding. Cox proportional hazards models were fitted to investigate associations between feeding practices (0-12 weeks) and infant HIV-free survival.

Results

Six hundred and sixty five HIV-positive and 218 HIV-negative women were recruited antenatally and followed-up until 36 weeks postpartum. Amongst mothers who breastfed between 3 weeks and 6 months postpartum, significantly more HIV-positive mothers practiced exclusive breastfeeding compared with HIV-negative: at 3 weeks 130 (42%) versus 33 (17%) (p < 0.01); this dropped to 17 (11%) versus 1 (0.7%) by four months postpartum. Amongst mothers practicing mixed breastfeeding between 3 weeks and 6 months postpartum, significantly more HIV-negative mothers used commercially available breast milk substitutes (p < 0.02) and use of these peaked between 9 and 12 weeks. The probability of postnatal HIV or death was lowest amongst infants living in the best resourced site who avoided breastfeeding, and highest amongst infants living in the rural site who stopped breastfeeding early (mean and standard deviations: 10.7% ± 3% versus 46% ± 11%).

Conclusions

Although feeding practices were poor amongst HIV-positive and -negative mothers, HIV-positive mothers undertake safer infant feeding practices, possibly due to counseling provided through the routine PMTCT programme. The data on differences in infant outcome by feeding practice and site validate the WHO 2009 recommendations that site differences should guide feeding practices amongst HIV-positive mothers. Strong interventions are needed to promote exclusive breastfeeding (to 6 months) with continued breastfeeding thereafter amongst HIV-negative motherswho are still the majority of mothers even in high HIV prevalence setting like South Africa.     

Measuring Population Transmission Risk for HIV: An Alternative Metric of Exposure Risk in Men Who Have Sex with Men (MSM) in the US

Background

Various metrics for HIV burden and treatment success [e.g. HIV prevalence, community viral load (CVL), population viral load (PVL), percent of HIV-positive persons with undetectable viral load] have important public health limitations for understanding disparities.

Methods and Findings

Using data from an ongoing HIV incidence cohort of black and white men who have sex with men (MSM), we propose a new metric to measure the prevalence of those at risk of transmitting HIV and illustrate its value. MSM with plasma VL>400 copies/mL were defined as having ‘transmission risk’. We calculated HIV prevalence, CVL, PVL, percent of HIV-positive with undetectable viral loads, and prevalence of plasma VL>400 copies/ml (%VL400) for black and white MSM. We used Monte Carlo simulation incorporating data on sexual mixing by race to estimate exposure of black and white HIV-negative MSM to a partner with transmission risk via unprotected anal intercourse (UAI). Of 709 MSM recruited, 42% (168/399) black and 14% (44/310) white MSM tested HIV-positive (p<.0001). No significant differences were seen in CVL, PVL, or percent of HIV positive with undetectable viral loads. The %VL400 was 25% (98/393) for black vs. 8% (25/310) for white MSM (p<.0001). Black MSM with 2 UAI partners were estimated to have 40% probability (95% CI: 35%, 45%) of having ≥1 UAI partner with transmission risk vs. 20% for white MSM (CI: 15%, 24%).

Discussion

Despite similarities in other metrics, black MSM in our cohort are three times as likely as white MSM to have HIV transmission risk. With comparable risk behaviors, HIV-negative black MSM have a substantially higher likelihood of encountering a UAI partner at risk of transmitting HIV. Our results support increasing HIV testing, linkage to care, and antiretroviral treatment of HIV-positive MSM to reduce prevalence of those with transmission risk, particularly for black MSM.     

Antibody responses to Cryptosporidium antigen in HIV-positive patients in the Republic of Korea

The diagnosis of cryptosporidiosis has been carried out using coprologic techniques in the Republic of Korea. However, antibody responses to Cryptosporidium have rarely been studied. Serum antibodies from HIV-positive/oocyst-positive Korean patients recognized significantly 31 and 27 kDa antigens, and HIV-negative/oocyst-positive individuals clearly reacted to 15/17 kDa antigens. Compared with oocyst-positive cases, 18.7% and 75.8% of sera from HIV-positive patients reacted to 31 and 27 kDa antigens. Only 11.1% of HIV-negative individuals reacted to 15/17 kDa. Based on these findings, serum antibody responses were different between HIV-positive and HIV-negative individuals infected with Cryptosporidium, and it is suggested that HIV-positive patients are more frequently exposed to C. parvum compared to HIV-negative individuals.     

T-SPOT.TB: an in vitro diagnostic assay measuring T-cell reaction to Mycobacterium tuberculosis-specific antigens

The overall sensitivity of the RD1 ELISPOT assay (T-SPO.TB), which counts T cells sensitized to specific Mycobacterium tuberculosis peptide sequences, was 81-97% in populations with confirmed tuberculosis, in whom 39-78% had immunosuppressive conditions. In patients with confirmed tuberculosis, the respective RD1 ELISPOT versus tuberculin skin test (TST) sensitivities were 100% versus 89% in adults and 77% versus 35% in children (of whom 39% were HIV-positive). In contrast to that of the TST, the sensitivity of the RD1 ELISPOT assay was not significantly affected by age <36 months, or the immunological or nutritional status of the subjects. Specificity was 100% in two UK-based studies. Isolated false positives have been recorded in patients infected with non-tuberculous M. kansasii. A study investigating latent tuberculosis infection found no significant difference in results between HIV-positive and -negative participants for the RD1 ELISPOT assay, while the TST varied significantly with HIV status. Contact-tracing studies have demonstrated concordance between the RD1 ELISPOT assay and the TST of 65-89%. There is a significant correlation between a positive result and the degree of exposure to the index case for the RD1 ELISPOT assay, but not for the TST, in contact-tracing studies. Unlike the TST, the RD1 ELISPOT assay is not confounded by bacille Calmette-Guérin vaccination.     

The High Cost of HIV-Positive Inpatient Care at an Urban Hospital in Johannesburg,South Africa

Background

While most HIV care is provided on an outpatient basis, hospitals continue to treat serious HIV-related admissions, which is relatively resource-intensive and expensive. This study reports the primary reasons for HIV-related admission at a regional, urban hospital in Johannesburg, South Africa and estimates the associated lengths of stay and costs.

Methods and Findings

A retrospective cohort study of adult, medical admissions was conducted. Each admission was assigned a reason for admission and an outcome. The length of stay was calculated for all patients (N = 1,041) and for HIV-positive patients (n = 469), actual utilization and associated costs were also estimated. Just under half were known to be HIV-positive admissions. Deaths and transfers were proportionately higher amongst HIV-positive admissions compared to HIV-negative and unknown. The three most common reasons for admission were tuberculosis and other mycobacterial infections (18%, n = 187), cardiovascular disorders (12%, n = 127) and bacterial infections (12%, n = 121). The study sample utilized a total of 7,733 bed days of those, 55% (4,259/7,733) were for HIV-positive patients. The average cost per admission amongst confirmed HIV-positive patients, which was an average of 9.3 days in length, was $1,783 (United States Dollars).

Conclusions

Even in the era of large-scale antiretroviral treatment, inpatient facilities in South Africa shoulder a significant HIV burden. The majority of this burden is related to patients not on ART (298/469, 64%), and accounts for more than half of all inpatient resources. Reducing the costs of inpatient care is thus another important benefit of expanding access to ART, promoting earlier ART initiation, and achieving rates of ART retention and adherence.     

Risk Factors for Vitamin D Deficiency among Veterans with and without HIV Infection

Objectives

We aimed to describe and compare the prevalence of vitamin D deficiency between HIV-negative and HIV-infected veterans in the southern United States, and to determine risk factors for vitamin D deficiency for HIV infected patients.

Methods

Cross-sectional, retrospective study including all patients followed at the Atlanta VA Medical Center with the first 25-hydroxyvitamin D [25(OH)D] level determined between January 2007 and August 2010. Multivariate logistic regression analysis was used to determine risk factors associated with vitamin D deficiency (< 20 ng/ml).

Results

There was higher prevalence of 25(OH)D deficiency among HIV-positive compared to HIV-negative patients (53.2 vs. 38.5%, p <0.001). Independent risk factors for vitamin D deficiency in HIV + patients included black race (OR 3.24, 95% CI 2.28–4.60), winter season (OR 1.39, 95% CI 1.05–1.84) and higher GFR (OR 1.01, CI 1.00–1.01); increasing age (OR 0.98, 95% CI 0.95–0.98), and tenofovir use (OR 0.72, 95% CI 0.54–0.96) were associated with less vitamin D deficiency.

Conclusions

Vitamin D deficiency is a prevalent problem that varies inversely with age and affects HIV-infected patients more than other veterans in care. In addition to age, tenofovir and kidney disease seem to confer a protective effect from vitamin D deficiency in HIV-positive patients.     

Contraceptive use and method preference among women in Soweto, South Africa: the influence of expanding access to HIV care and treatment services

Objective

Preventing unintended pregnancy among HIV-positive women constitutes a critical and cost-effective approach to primary prevention of mother-to-child transmission of HIV and is a global public health priority for addressing the desperate state of maternal and child health in HIV hyper-endemic settings. We sought to investigate whether the prevalence of contraceptive use and method preferences varied by HIV status and receipt of highly active antiretroviral therapy (HAART) among women in Soweto, South Africa.

Methods

We used survey data from 563 sexually active, non-pregnant women (18–44 years) recruited from the Perinatal HIV Research Unit in Soweto (May–December, 2007); 171 women were HIV-positive and receiving HAART (median duration of use = 31 months; IQR = 28, 33), 178 were HIV-positive and HAART-naïve, and 214 were HIV-negative. Medical record review was conducted to confirm HIV status and clinical variables. Logistic regression models estimated adjusted associations between HIV status, receipt of HAART, and contraceptive use.

Results

Overall, 78% of women reported using contraception, with significant variation by HIV status: 86% of HAART users, 82% of HAART-naïve women, and 69% of HIV-negative women (p<0.0001). In adjusted models, compared with HIV-negative women, women receiving HAART were significantly more likely to use contraception while HAART-naïve women were non-significantly more likely (AOR: 2.40; 95% CI: 1.25, 4.62 and AOR: 1.59; 95% CI: 0.88, 2.85; respectively). Among HIV-positive women, HAART users were non-significantly more likely to use contraception compared with HAART-naïve women (AOR: 1.55; 95% CI: 0.84, 2.88). Similar patterns held for specific use of barrier (primarily male condoms), permanent, and dual protection contraceptive methods.

Conclusion

Among HIV-positive women receiving HAART, the observed higher prevalence of contraceptive use overall and condoms in particular promises to yield fewer unintended pregnancies and reduced risks of vertical and sexual HIV transmission. These findings highlight the potential of integrated HIV and reproductive health services to positively impact maternal, partner, and child health.     

Serologic Responses to Recombinant Pneumocystis jirovecii Major Surface Glycoprotein among Ugandan Patients with Respiratory Symptoms

Background

Little is known about the serologic responses to Pneumocystis jirovecii major surface glycoprotein (Msg) antigen in African cohorts, or the IgM responses to Msg in HIV-positive and HIV-negative persons with respiratory symptoms.

Methods

We conducted a prospective study of 550 patients, both HIV-positive (n = 467) and HIV-negative (n = 83), hospitalized with cough ≥2 weeks in Kampala, Uganda, to evaluate the association between HIV status, CD4 cell count, and other clinical predictors and antibody responses to P. jirovecii. We utilized ELISA to measure the IgM and IgG serologic responses to three overlapping recombinant fragments that span the P. jirovecii major surface glycoprotein: MsgA (amino terminus), MsgB (middle portion) and MsgC1 (carboxyl terminus), and to three variations of MsgC1 (MsgC3, MsgC8 and MsgC9).

Results

HIV-positive patients demonstrated significantly lower IgM antibody responses to MsgC1, MsgC3, MsgC8 and MsgC9 compared to HIV-negative patients. We found the same pattern of low IgM antibody responses to MsgC1, MsgC3, MsgC8 and MsgC9 among HIV-positive patients with a CD4 cell count <200 cells/µl compared to those with a CD4 cell count ≥200 cells/µl. HIV-positive patients on PCP prophylaxis had significantly lower IgM responses to MsgC3 and MsgC9, and lower IgG responses to MsgA, MsgC1, MsgC3, and MsgC8. In contrast, cigarette smoking was associated with increased IgM antibody responses to MsgC1 and MsgC3 but was not associated with IgG responses. We evaluated IgM and IgG as predictors of mortality. Lower IgM responses to MsgC3 and MsgC8 were both associated with increased in-hospital mortality.

Conclusions

HIV infection and degree of immunosuppression are associated with reduced IgM responses to Msg. In addition, low IgM responses to MsgC3 and MsgC8 are associated with increased mortality.