Evaluation of two methods of bone age assessment in peripubertal children in Zimbabwe.

OBJECTIVES: Bone age (BA) measurement in children is used to evaluate skeletal maturity and helps in the diagnosis of growth disorders in children. The two most used methods are Greulich and Pyle (GP), and Tanner and Whitehouse 3 (TW3), both based upon assessment of a hand-wrist radiograph. To our knowledge no study has compared and validated the two methods in sub-Saharan Africa (SSA), and only a few have determined BA despite it being a region where skeletal maturity is often impaired for example by HIV and malnutrition. This study aimed to compare BA as measured by two methods (GP and TW3) against chronological age (CA) and determine which method is most applicable in peripubertal children in Zimbabwe. METHODS: We conducted a cross-sectional study of boys and girls who tested negative for HIV. Children and adolescents were recruited by stratified random sampling from six schools in Harare, Zimbabwe. Non-dominant hand-wrist radiographs were taken, and BA assessed manually using both GP and TW3. Paired sample Student t-tests were used to calculate the mean differences between BA and chronological age (CA) in boys and girls. Bland-Altman plots compared CA to BA as determined by both methods, and agreement between GP and TW3 BA. All radiographs were graded by a second radiographer and 20 % of participants of each sex were randomly selected and re-graded by the first observer. Intraclass correlation coefficient assessed intra- and inter-rater reliability and coefficient of variation assessed precision. RESULTS: We recruited 252 children (111 [44 %] girls) aged 8.0-16.5 years. The boys and girls were of similar mean ± SD CA (12.2 ± 2.4 and 11.7 ± 1.9 years) and BA whether assessed by GP (11.5 ± 2.8 and 11.5 ± 2.1 years) or TW3 (11.8 ± 2.5 and 11.8 ± 2.1 years). In boys BA was lower than CA by 0.76 years (95 % CI: -0.95, -0.57) when using GP, and by 0.43 years (95 % CI: -0.61, -0.24) when using TW3. Among the girls there was no difference between BA and CA by either GP [-0.19 years (95 % CI: -0.40, 0.03)] or TW3 [0.07 years (95 % CI: -0.16, 0.29)]. In both boys and girls, there were no systematic differences between CA and TW3 BA across age groups whereas agreement improved between CA and GP BA as children got older. Inter-operator precision was 1.5 % for TW3 and 3.7 % for GP (n = 252) and intra-operator precision was 1.5 % for TW3 and 2.4 % for GP (n = 52). CONCLUSION: The TW3 BA method had better precision than GP and did not systematically differ from CA, meaning that TW3 is the preferred method of assessment of skeletal maturity in Zimbabwean children and adolescents. TW3 and GP methods do not agree for estimates of BA and therefore cannot be used interchangeably. The systematic differences in GP BA assessments over age means it is not appropriate for use in all age groups or stages of maturity in this population.

Development of retinal structure in perinatally HIV-infected children and adolescents: A longitudinal and cross-sectional assessment.

In perinatally HIV-infected (PHIV) children, cross-sectional studies reported on subtle structural retinal differences and found associations between the retina and structural brain changes. Our objective is to investigate whether neuroretinal development in PHIV children is similar to the development in healthy matched controls and to explore associations with the brain structure. We measured RT using optical coherence tomography (OCT) on two occasions in 21 PHIV children or adolescents and 23 matched controls-all with good visual acuity-with a mean interval of 4.6 years (SD 0.3). We also included 22 participants (11 PHIV children and 11 controls) together with the follow-up group for a cross-sectional assessment using a different OCT device. Magnetic resonance imaging (MRI) was used to assess the white matter microstructure. We used linear (mixed) models to assess changes in RT and its determinants (over time), adjusting for age and sex. The development of the retina was similar between the PHIV adolescents and controls. In our cohort, we found that changes in the peripapillary RNFL was significantly associated with changes in WM microstructural makers: fractional anisotropy (coefficient = 0.030, p = 0.022) and radial diffusivity (coefficient = -0.568, p = 0.025). We found comparable RT between groups. A thinner pRNFL was associated with lower WM volume (coefficient = 0.117, p = 0.030). PHIV children or adolescents appear to have a similar development of the retinal structure. In our cohort, the associations between RT and MRI biomarkers underscore the relation between retina and brain.

Comparison of quantitative ultrasonography and dual X-ray absorptiometry for bone status assessment in South African children living with HIV.

Children living with HIV (CLHIV) have decreased bone mineral content (BMC) and density (BMD), increasing risk for fracture and future osteoporosis. While DXA is the gold-standard for bone assessments, it lacks availability in resource-constrained settings (RCS). Quantitative ultrasound (QUS) offers an alternative owing to its portability, low cost, ease of handling, and lack of ionizing radiation. While QUS has detected reduced bone quality in CLHIV, the relationship between QUS and DXA in this population remains unexplored. At baseline and 12 months, BMC and BMD of the whole body, lumbar spine, and radius were measured by DXA in a longitudinal cohort of CLHIV in Johannesburg, South Africa. Calcaneal speed of sound (SOS) and broadband ultrasound attenuation (BUA) and radius SOS were obtained by QUS, and calcaneal stiffness index (SI) was calculated. Spearman correlations, with and without HIV stratification, were performed between QUS and DXA measurements at each visit and for absolute difference in measurements between visits. At baseline and 12-months, calcaneal BUA and SI displayed strong positive correlations with DXA, with only modest correlations between radial QUS and DXA at baseline. Longitudinal measures of QUS did not correlate with DXA. At both baseline and 12-months, individuals with DXA whole-body BMD z-score < -1 displayed significantly lower calcaneal BUA and SI. Cross-sectionally, calcaneal QUS correlates strongly with whole body DXA and may represent a viable diagnostic alternative in RCS. Longitudinally, the two methods do not correlate well, possibly reflecting that each method assesses distinct aspects of bone architecture.

Echocardiographic assessment of asymptomatic US Air Force members with early HIV infection.

OBJECTIVE: People living with HIV (PLHIV) are at increased risk for cardiovascular disease (CVD) and development of subclinical echocardiographic abnormalities. However, there is scant evidence of the echocardiographic changes that occur shortly after seroconversion. In this study we describe the echocardiographic evaluations of asymptomatic US Air Force members who were diagnosed with HIV infection and evaluated at the San Antonio Military Medical Center between September 1, 2015 and September 30, 2016. RESULTS: Patients (n = 50) were predominantly male (96%), mostly African American (60%), with a mean age of 28 years. At HIV diagnosis, the mean viral load was 112,585 copies/mL and CD4 count was 551 cells/µL. All were found to have normal left ventricular systolic ejection fraction (EF) and global longitudinal strain (GLS) however evidence of right ventricular dilatation and left ventricular remodeling was observed in 7 (14%) and 13 (26%) patients, respectively. Subgroup analyses showed no significant differences in echocardiographic findings by HIV disease severity or CVD risk factors (p > 0.05 for all).This study suggests that untreated HIV may have a low impact on the development of echocardiographic abnormalities shortly after seroconversion. Longitudinal studies are warranted to determine the optimal CVD risk assessment strategies for PLHIV.

Assessment of trabecular bone score, an index of bone microarchitecture, in HIV positive and HIV negative persons within the HIV UPBEAT cohort.

INTRODUCTION: Increased prevalence of low bone mineral density (BMD) and increased fracture incidence are observed in persons living with HIV (PLWH). The trabecular bone score (TBS) is a novel index of bone microarchitecture which improves fracture prediction independent of BMD. METHODS: The HIV UPBEAT study is a single centre, prospective cohort study that enrolled subjects with and without HIV from similar sociodemographic backgrounds for annual assessments of bone health. TBS was derived from lumbar spine (LS) dual-energy X-ray absorptiometry images. Univariate and multivariable linear regression was used to assess relationships between baseline TBS, BMD, sociodemographic and clinical factors. RESULTS: 463 subjects (201 HIV positive) were included; PLWH were younger and more likely male, of non-African ethnicity and current smokers. HIV was associated with a mean reduction of 0.037 [-0.060, -0.013] (p = 0.002) in TBS. Lower TBS was also associated with male gender, non-African ethnicity, current smoking status and lower LS BMD. HIV remained associated with lower TBS after adjustment for LS BMD, age, gender and ethnicity. However, adjustment for current smoking significantly attenuated the association between HIV and TBS, with further adjustment for higher bone turnover markers largely explaining any residual association. Among the sub-group of PLWH, exposure to protease inhibitors and lower nadir CD4+ T-cell counts were both predictors of lower TBS. CONCLUSIONS: PLWH have lower TBS independent of LS BMD. However, this is largely explained by higher current smoking rates and higher bone turnover in those with HIV. Exposure to PI, but not tenofovir disproxil fumarate, also contributed to lower TBS in those with HIV.

Optimizing HIV testing services in sub-Saharan Africa: cost and performance of verification testing with HIV self-tests and tests for triage.

INTRODUCTION: Strategies employing a single rapid diagnostic test (RDT) such as HIV self-testing (HIVST) or "test for triage" (T4T) are proposed to increase HIV testing programme impact. Current guidelines recommend serial testing with two or three RDTs for HIV diagnosis, followed by retesting with the same algorithm to verify HIV-positive status before anti-retroviral therapy (ART) initiation. We investigated whether clients presenting to HIV testing services (HTS) following a single reactive RDT must undergo the diagnostic algorithm twice to diagnose and verify HIV-positive status, or whether a diagnosis with the setting-specific algorithm is adequate for ART initiation. METHODS: We calculated (1) expected number of false-positive (FP) misclassifications per 10,000 HIV negative persons tested, (2) positive predictive value (PPV) of the overall HIV testing strategy compared to the WHO recommended PPV ≥99%, and (3) expected cost per FP misclassified person identified by additional verification testing in a typical low-/middle-income setting, compared to the expected lifetime ART cost of $3000. Scenarios considered were as follows: 10% prevalence using two serial RDTs for diagnosis, 1% prevalence using three serial RDTs, and calibration using programmatic data from Malawi in 2017 where the proportion of people testing HIV positive in facilities was 4%. RESULTS: In the 10% HIV prevalence setting with a triage test, the expected number of FP misclassifications was 0.86 per 10,000 tested without verification testing and the PPV was 99.9%. In the 1% prevalence setting, expected FP misclassifications were 0.19 with 99.8% PPV, and in the Malawi 2017 calibrated setting the expected misclassifications were 0.08 with 99.98% PPV. The cost per FP identified by verification testing was $5879, $3770, and $24,259 respectively. Results were sensitive to assumptions about accuracy of self-reported reactive results and whether reactive triage test results influenced biased interpretation of subsequent RDT results by the HTS provider. CONCLUSIONS: Diagnosis with the full algorithm following presentation with a reactive triage test is expected to achieve PPV above the 99% threshold. Continuing verification testing prior to ART initiation remains recommended, but HIV testing strategies involving HIVST and T4T may provide opportunities to maintain quality while increasing efficiency as part of broader restructuring of HIV testing service delivery.

Promoting high standards of care for women living with HIV: position statement from the Women Against Viruses in Europe Working Group.

OBJECTIVES: Gender-related factors can influence management decisions, treatment outcomes and the overall long-term wellbeing of people living with HIV (PLWH). The Women Against Viruses in Europe (WAVE) Working Group was established to promote the health and wellbeing of women living with HIV (WLWH). WAVE is part of the European AIDS Clinical Society (EACS) and organizes annual workshops to discuss different issues in the management of WLWH. METHODS: In 2016, 34 WAVE members including community representatives, HIV clinicians and researchers met to discuss standards of care for WLWH and to review current guidelines. Participants focused on three different themes: (1) access to and engagement and retention in care; (2) monitoring of women on antiretroviral therapy and management of comorbidities; and (3) review of EACS treatment guidelines. RESULTS: Five priority areas for optimizing the care of WLWH were identified: (1) psychosocial aspects of HIV diagnosis and care; (2) mental health and wellbeing; (3) pharmacokinetics, toxicity and tolerability of antiretroviral therapy; (4) coinfections and comorbidities; and (5) sexual and reproductive health. WAVE recommendations are provided for each of these areas, and gaps in knowledge and needs for changes in currently existing standards are discussed. CONCLUSIONS: This position statement provides an overview of the key recommendations to optimize the care of WLWH that emerged during the 2016 WAVE workshop.

Cocaine and HIV are independently associated with neural activation in response to gain and loss valuation during economic risky choice.

Stimulant abuse is disproportionately common in HIV-positive persons. Both HIV and stimulants are independently associated with deficits in reward-based decision making, but their interactive and/or additive effects are poorly understood despite their prevalent co-morbidity. Here, we examined the effects of cocaine dependence and HIV infection in 69 adults who underwent functional magnetic resonance imaging while completing an economic loss aversion task. We identified two neural networks that correlated with the evaluation of the favorable characteristics of the gamble (i.e. higher gains/lower losses: ventromedial prefrontal cortex, anterior cingulate, anterior and posterior precuneus and visual cortex) versus unfavorable characteristics of the gamble (i.e. lower gains/higher losses: dorsal prefrontal, lateral orbitofrontal, posterior parietal cortex, anterior insula and dorsal caudate). Behaviorally, cocaine and HIV had additive effects on loss aversion scores, with HIV-positive cocaine users being the least loss averse. Cocaine users had greater activation in brain regions that tracked the favorability of gamble characteristics (i.e. increased activation to gains, but decreased activation to losses). In contrast, HIV infection was independently associated with lesser activation in regions that tracked the unfavorability of gamble characteristics. These results suggest that cocaine is associated with an overactive reward-seeking system, while HIV is associated with an underactive cognitive control system. Together, these alterations may leave HIV-positive cocaine users particularly vulnerable to making unfavorable decisions when outcomes are uncertain.

Effects of social adversity and HIV on subcortical shape and neurocognitive function.

The purpose of the current study was to examine the independent and interactive effects of social adversity (SA) and HIV infection on subcortical shape alterations and cognitive functions. Participants included HIV+ (n = 70) and HIV- (n = 23) individuals who underwent MRI, neurocognitive and clinical assessment, in addition to completing questionnaires from which responses were used to create an SA score. Bilateral amygdalae and hippocampi were extracted from T1-weighted images. Parametric statistical analyses were used to compare the radial distance of the structure surface to a median curve to determine the presence of localized shape differences as a function of HIV, SA and their interaction. Next, multiple regression was used to examine the interactive association between HIV and SA with cognitive performance data. An HIV*SA interactive effect was found on the shape of the right amygdala and left hippocampus. Specifically, HIV-infected participants (but not HIV-uninfected controls) who evidenced higher levels of SA displayed an inward deformation of the surface consistent with reduced volume of these structures. We found interactive effects of HIV and SA on learning/memory performance. These results suggest that HIV+ individuals may be more vulnerable to neurological and cognitive changes in the hippocampus and amygdala as a function of SA than HIV- individuals, and that SA indicators of childhood SES and perceived racial discrimination are important components of adversity that are associated with cognitive performance.

PPACA and Low-Income People Living with HIV: 2014 Qualified Health Plan Enrollment in a Medicaid Nonexpansion State.

People living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) often are uninsured or underinsured, and they may benefit from the Patient Protection and Affordable Care Act (PL 111-148) and its improved access to medical care. Safety net programs, such as AIDS Drug Assistance Programs (ADAP) funded through the Ryan White HIV/AIDS Program, which serve low-income people living with HIV, are incorporating Patient Protection and Affordable Care Act Marketplace-qualified health plans (QHPs) and helping to fund patients' participation. This changing landscape differs from state to state, and one main element contributing to the differing situations is whether a state elected to expand Medicaid. This review examines QHP enrollment of ADAP clients in Virginia, a Medicaid nonexpansion state, and explores some issues that affect people living with HIV in other Medicaid nonexpansion states. Virginia is a leader in the shift of ADAP healthcare delivery from direct medication provision to purchasing QHPs. Virginia ADAP clients accounted for approximately 2% of ADAP clients nationally, but they represent 17% of ADAP clients enrolled in QHPs nationwide. Ensuring good HIV care of the ADAP population is important to each patient's personal longevity, the public health, and the efficient use of healthcare dollars. As healthcare delivery models shift, the effects on patients and health outcomes achieved should be monitored, particularly for chronic diseases such as HIV.

Assessment of radiological vertebral fractures in HIV-infected patients: clinical implications and predictive factors.

OBJECTIVES: The aim of this study was to evaluate the clinical impact of including lateral spine X-ray in the screening of bone diseases in HIV-positive patients. METHODS: A total of 194 HIV-positive patients underwent dual-energy X-ray absorptiometry (DEXA), lateral spine X-ray and bone biochemical analysis. Vertebral fractures were identified using a morphometric analysis of X-rays and classified using the semiquantitative scoring system of Genant et al. For each patient, a spine deformity index (SDI) score was calculated by summing the grades of vertebral deformities. Reductions in vertebral body height of > 25% were considered vertebral fractures, and those < 25% were considered vertebral deformities. Risk factors associated with vertebral fractures were evaluated by univariate and multivariate analysis. RESULTS: Vertebral fractures were detected in 24 patients (12.4%) and vertebral deformities in 17 patients (8.7%); 153 patients (78.9%) did not show any vertebral deformity. Among patients with fractures, only two with SDI > 10 reported lumbar pain; the remaining were asymptomatic. Patients over 50 years old showed a higher prevalence of vertebral fracture [24.4% versus 11.8% in patients 41-50 years old (P = 0.05) and 1.9% in patients ≤ 40 years old (P = 0.04)]. No significant increase in the prevalence according to bone mineral density (BMD) reduction was observed, and 70% of fractures were diagnosed in nonosteoporotic patients. Older age [adjusted odds ratio 1.09; 95% confidence interval (CI) 1.03-1.13; P = 0.001] and steroid use (adjusted odds ratio 3.64; 95% CI 1.29-10.3; P = 0.01) were independently associated with vertebral fracture; no association was found with HIV- or highly active antiretroviral therapy (HAART)-related variables. CONCLUSIONS: A prevalence of vertebral fractures of 12.4% was observed in our HIV-positive cohort. Given that two-thirds of fractures occurred in nonosteoporotic patients, spine X-ray may be considered in patients at increased risk, irrespective of BMD; that is, in elderly patients and/or patients using steroids.

Cost-effectiveness of point-of-care digital chest-x-ray in HIV patients with pulmonary mycobacterial infections in Nigeria.

BACKGROUND: Chest-x-ray is routinely used in the diagnosis of smear negative tuberculosis (TB). This study assesses the incremental cost per true positive test of a point-of-care digital chest-x-ray, in the diagnosis of pulmonary mycobacterial infections among HIV patients with presumed tuberculosis undetected by smear microscopy. METHODS: Consecutive patients with clinical suspicion of pulmonary tuberculosis were serially tested for Human immunodeficiency virus (HIV), their sputum examined for Acid Fast Bacilli then cultured in broth and solid media. Cultures characterized as tuberculous (M.tb) and non-tuberculous (NTM) mycobacteria by Hain assays were used as gold standards. A chest-x-ray was classified as: (1) consistent for TB, (2) not consistent for TB and (3) no pathology. RESULTS: Of the 1391 suspected cases enrolled, complete data were available for 952 (68%): 753/952 (79%) had negative smear tests while 150/753 (20%) had cultures positive for TB. Of those, 82/150 (55%) had chest-x-ray signs consistent with TB and 29/82 (35%) were positive for HIV. Within the co-infected, 9/29 (31%) had NTM infections. Among all suspects, the cost per positive case detected using smear microscopy test was $52.84; the overall incremental cost per positive case using chest-x-ray in smear negatives was $23.42, and in smear negative, HIV positive patients the cost was $15.77. CONCLUSION: Point-of-care chest-x-ray is a cost-effective diagnostic tool for smear negative HIV positive patients with pulmonary mycobacterial infection.

Short course for focused assessment with sonography for human immunodeficiency virus/tuberculosis: preliminary results in a rural setting in South Africa with high prevalence of human immunodeficiency virus and tuberculosis.

In Africa, human immunodeficiency virus (HIV)-associated extrapulmonary tuberculosis (TB) is common and poses diagnostic difficulties. Ultrasound is useful to find suggestive signs such as effusions or abdominal lymphadenopathy. Because trained radiologists are scarce in resource-poor settings, even this simple and relatively inexpensive diagnostic tool is frequently unavailable to patients in district hospitals in sub-Saharan Africa. We developed a focused protocol for assessment with sonography for HIV/TB and trained physicians in a rural district hospital in South Africa. In this pilot study, high levels of confidence in identifying specific signs were rapidly achieved and ultrasound was introduced into routine clinical practice.

Utility of abdominal ultrasonography in HIV patients.

INTRODUCTION: Various diseases associated with human immunodeficiency virus (HIV) infection are often difficult to diagnose. A poor immune response, atypical presentations and opportunistic pathologies all contribute to this difficulty. We tried to evaluate the utility of routine abdominal ultrasonography (US) in new and follow-up HIV cases, and compared the results among those with a clinical need for US and those where US was performed as a routine screening. METHODS: 150 consecutive seropositive patients were subdivided into four groups depending on the necessity of abdominal US on the initial workup, i.e. Group A (38 patients) or B (112 patients), and whether they were newly-diagnosed HIV patients or follow-up patients, i.e. Group X (62 patients) or Y (88 patients), giving us subgroups, AX (22 patients), AY (16 patients), BX (40 patients) and BY (72 patients). RESULTS: The prevalence of significant US findings was higher in those with CD4 less than 200 cells/ml (77.8 percent) compared to those with CD4 200-500 cells/ml and CD4 more than 500 cells/ml (65.5 percent and 37 percent, respectively). 24 out of 38 patients with clinical indications and 71 out of 112 patients without any obvious clinical need for US, had positive findings on US, the majority of which had a major therapeutic impact. CONCLUSION: We conclude that abdominal US is a simple and cost-effective tool in resource-poor countries like India, where HIV care is becoming more and more important.

[Abdominal echography in patients with human immunodeficiency virus (HIV) infection. Diagnostic usefulness in the evaluation of associated medico-surgical pathology]. / Ecografía abdominal en el paciente con infeción por el virus de la inmunodeficiencia humana (VIH). Utilidad diagnóstica en la valoración de la patología médico-quirúrgica asociada.

BASIS: The abdominal manifestations in the patient with HIV infection are increasingly frequent. We have conducted the present study in order to determine the diagnostic usefulness of the abdominal echography in the clinical assessment of the patient. MATERIALS AND METHODS: We review the echographic findings of 112 patients carrying the HIV with or without the Acquired Immunodeficiency Syndrome (AIDS). Seventy eight patients were men and 34, women, with an average age of 30 years. The main risk group was parenterally drug addiction (72%). The stage of the HIV infection was IVC1 in 41% of the cases, II in 23%, III in 13% and IVC2 in 13%. The echographic exploration was performed using a real-time echography, with a probe of 3.5 Mhz, assessing according to conventional criteria the abdominal organs and their pathology, masses and free intraabdominal fluid. The echographic characteristics were first broadly assessed in the patients from the series and later on, according to the patient's pathology. (Infectious, acute abdominal, hepatic biochemical disorders, HIV carrier-associated pathology). RESULTS: In 33% of the cases, the echography was normal. Hepatomegaly was the most frequent echographic sign: 56 patients (50%), followed by splenomegaly in 43 patients (38.3%), standing out the affection of the biliary and/or vesicular ductus in 7 patients (6.2%). The echographic findings were not related to the HIV infection stage, nor with the presence of hepatic biochemical disorders. However, the presence of organomegaly (hepatosplenomegaly associated or not to retroperitoneal adenopathies) were more frequent in the group with infectious complication, 33.3% vs 19.6% (p < 0.01), that in the patients without associated infectious processes. In patients with medical or surgical acute abdominal pathology, the echography was diagnostic in 9 out of 10 patients. CONCLUSION: In the HIV patient, the echography allows an specific initial diagnostic assessment, being able in most of the patients with abdominal manifestations to diagnose the causal pathology.