Association between rectal gonorrhoea and HIV incidence in men who have sex with men: a meta-analysis

BackgroundIncidence of rectal gonorrhoea (GC) has been hypothesised as a correlate of HIV exposure in prevention trials of men who have sex with men (MSM). High rectal GC incidence in MSM trials of new biomedical prevention drugs may provide supportive evidence for ongoing HIV risk. Empirical evidence of correlation between rectal GC and HIV incidence is needed to assess whether high rectal GC rates reliably correlate with high risk of HIV.MethodsRectal GC and HIV are routinely tested in sexual health clinics (SHCs) throughout England. Through routine surveillance data collected at visits to SHCs, we assessed HIV incidence and new rectal GC diagnoses in repeat visits by HIV-negative MSM between 2011 and 2018, predating widespread roll-out of pre-exposure prophylaxis. Meta-analysis regression assessed population-level association between HIV and rectal GC incidence over time.FindingsBetween 2011 and 2018, HIV and rectal GC incidence was assessed in 541 056 HIV-negative MSM attending SHCs in England. HIV incidence among MSM attending SHCs fell from 1.26/100 person-years (PYs) in 2011 to 0.28/100 PYs in 2018. Rectal GC rates increased from 3.5/100 PYs to 11.1/100 PYs over the same period. The rate of HIV incidence decreased by 22.3% for each percent increase in rectal GC (95% CI –30.8 to –14.7, p<0.001).InterpretationAmong the population of MSM attending SHCs in England, rectal GC rates increased substantially while HIV incidence rates decreased between 2011 and 2018. HIV incidence likely decreased through expanded HIV testing, prompt antiretroviral treatment (ART) initiation and increased viral suppression in persons living with HIV, interventions that did not decrease rectal GC. Rectal GC may not be an ideal proxy for HIV incidence in trials, as HIV exposure risk is complex and context dependent, given effective HIV prevention interventions in MSM.Introduction

The Moral Reading of HIV Prevention in the United States: Criminal Law and Tort Law

The United States government has been campaigning to encourage people to take HIV testing and thus get treated. It is puzzling that more than 50% of States have HIV-specific criminal laws that criminalize both exposure and transmission. At the same time, there is an increased tort law to seek financial compensation for unwanted HIV exposure and transmission. While both laws the moral claim of protecting people from HIV infection, this paper is trying to find an answer to the following inquiry: What is the difference of the moral reading between the use of criminal law and tort law in addressing HIV prevention in the United States? This paper uses the traditional descriptive comparison between criminal law and tort law under the American legal system with a nationwide jurisdictional scope. This paper measures the difference using the frame of reference of Ronald Dworkin's law, morality, and interpretation theory. Both criminal law and tort law have been developing similar liability principles regarding HIV exposure and transmission under the United States' common law tradition. For HIV prevention itself, both criminal law and tort law play a marginal role in gaining public health purposes in reversing the HIV epidemic. Criminal law has been scrutinized as not aligned with the purpose of law where misconceptions exist in both substantive dimension and the underlying moral claim. Tort law, on the other hand, suffers an even less moral claim on public health purposes. However, tort law maintains a consistent narrow sense of financial liability.

Clinical pneumonia in the hospitalised child in Malawi in the post-pneumococcal conjugate vaccine era: a prospective hospital-based observational study

Objective Assess characteristics of clinical pneumonia after introduction of pneumococcal conjugate vaccine (PCV), by HIV exposure status, in children hospitalized in a governmental hospital in Malawi. Methods and findings We evaluated 1,139 children ≤5 years old hospitalised with clinical pneumonia: 101 HIV-exposed uninfected (HEU) and 1038 HIV-unexposed, uninfected (HUU). Median age was 11 months (IQR 6-20), 59% were male, median mid-upper arm circumference (MUAC) was 14 cm (IQR 13-15) and mean weight-for-height z score was -0.7 (+/-2.5). The highest Respiratory Index of Severity in Children (RISC) scores were allocated to 10.4% of the overall cohort, respectively. Only 45.7% had fever, and 37.2% had at least one danger sign at presentation. The most common clinical features were crackles (54.7%), nasal flaring (53.5%), and lower chest wall indrawing (53.2%). Compared to HUU, HEU children were significantly younger (9 months v. 11 months), with lower mean birth weight (2.8 kg v. 3.0 kg) and MUAC (13.6 cm v. 14.0 cm), had higher prevalence of vomiting (32.7% v. 22.0%), tachypnoea (68.4% v. 49.8%), and highest RISC scores (20.0% v. 9.4%). Five children died (0.4%). However, clinical outcomes were similar for both groups. Conclusions In this post-PCV setting where prevalence of HIV and malnutrition is high, children hospitalised fulfilling the WHO Integrated Management of Childhood Illness criteria for clinical pneumonia present with heterogeneous features. These vary by HIV exposure status but this does not influence either the frequency of danger signs or mortality. The poor performance of available severity scores in this population and the absence of more specific diagnostics hinder appropriate antimicrobial stewardship and the rational application of other interventions.

Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of highly active anti-retroviral therapy

HIV-Exposed Uninfected (HEU) infants are a rapidly expanding population in Sub Saharan Africa and are highly particularly susceptible to disease caused by encapsulated bacteria in the first year of life. The mechanism of this increased risk is still poorly understood and we therefore, investigated if HIV exposure dysregulates HEU infant immunity and if this is amplified by human herpes infection (HHV). Here, we compared monocyte enzymatic function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HUU infants. We demonstrate altered monocyte phagosomal function and B cell subset homeostasis, and lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-Tetanus Toxoid (TT) IgG titers in HEU compared to HUU infants. There was no difference in the prevalence of HHV infection between HEU and HUU infants. Our findings suggest that even in the era of ART-mediated viral suppression, HIV exposure dysregulates monocyte and B cell function during a vulnerable period of immune maturation in infancy. This may contribute to the high rates of bacterial disease and pneumonia in HEU infants.

Disentangling the Role of HIV Exposure on Linear Growth Among Mother-Infant Dyads in Western Kenya: A Comparison of Three Growth Models

Objectives HIV-exposed and uninfected (HEU) infants may experience altered growth compared to HIV-unexposed and uninfected (HUU) infants. Most studies to date have used analytic techniques that do not reflect the dynamic trends in infant growth patterns. We therefore sought to evaluate growth patterns using 3 different analytic methods and examine the role of HIV on growth with each method. Methods Repeated measures for infant anthropometrics were taken from 6 wk to 23 mo of age in the former Nyanza region, Kenya (n = 310, 52% HEU, 50% male). We used (1) Latent Class Mixed Modeling (LCMM) to identify length-for-age z-score (LAZ) trajectory classes and then multinomial logistic regression to assess how HIV exposure status predicted trajectory class membership, adjusting for covariates (e.g., maternal height, food insecurity); (2) SuperImposition by Translation and Rotation (SITAR) to estimate length in terms of size and velocity (rate of growth) differences by maternal HIV status; and (3) longitudinal regression, the conventional method for analyzing growth, to estimate differences in length and LAZ based on HIV exposure. Results At 6 wks of age, HEU infants had a mean LAZ score of −1.03 ± 1.85 compared to −1.10 ± 1.83 for HUU infants. LCMM identified four LAZ trajectory classes (average 5.1 measurements/infant). Across time, class one LAZ scores remained near 1; class two declined 0 to −1; class three remained near −1; and class four fluctuated between −2 and −3. In logistic regression models, HEU infants were less likely to belong to classes one (RR = 0.3; 95% CI: 0.1,0.9) and two (RR = 0.4; 95% CI: 0.2,0.7) relative to class three. Similarly, SITAR estimated that HEU infants were on average 0.62 cm shorter than HUU infants across the study (95% CI: −1.3,0.1) but there were no differences in mean linear growth velocities. Longitudinal regression models predicted that mean stature for HEU infants was 0.8 cm (95% CI: −1.5, −0.1) shorter and that mean LAZ for HEU infants was 0.4 points (95% CI: −0.7, −0.1) lower compared to HUU infants. Conclusions Across the 3 methods, HEU infants were shorter than HUU infants during the first 23 mo of life. Compared to longitudinal regression, advanced modeling with LCMM and SITAR allows for a more flexible assessment of the altered growth patterns HEU infants experience. Funding Sources NIH.

The utility of a modified W.H.O. TB screening tool among children at a Botswana child welfare clinic

Background: In high TB/HIV settings, the increased risk for TB amongst children exposed to HIV has been established through biomedical tests. Screening HIV exposed children for TB can improve early childhood TB detection and treatment. Objective: This study assessed the utility of a modified World Health Organization (WHO) tool by including HIV variables, to determine TB exposure amongst HIV exposed children presenting to a “Well Child” Clinic (CWC). Methods: Clinical data were obtained from medical records and/or from the caregivers of children presenting to CWC. Data was analyzed to explore factors associated with positive screening for TB, including being exposed to HIV and current HIV status. Results: Five percent (55/1100) screened reported a close TB contact and 21% (n=231) had positive TB symptom screen. History of close TB contact was a risk factor for positive screening for TB symptoms (OR 1.89 CI 1.05-3.4) while being HIV negative was protective (OR 0.3, Cl 0.19-0.62). HIV exposure was associated with increased risk of TB exposure (OR 2.9 CI 1.61-5.19). Conclusion: Integrating HIV variables in the existing WHO screening tool for childhood TB can be useful in early detec- tion and treatment of TB in HIV exposed children in resource limited settings. Keywords: Childhood TB screening; HIV Exposure screening; TB/HIV integration.

The utility of a modified W.H.O. TB screening tool among children at a Botswana child welfare clinic

Background: In high TB/HIV settings, the increased risk for TB amongst children exposed to HIV has been established through biomedical tests. Screening HIV exposed children for TB can improve early childhood TB detection and treatment. Objective: This study assessed the utility of a modified World Health Organization (WHO) tool by including HIV variables, to determine TB exposure amongst HIV exposed children presenting to a “Well Child” Clinic (CWC). Methods: Clinical data were obtained from medical records and/or from the caregivers of children presenting to CWC. Data was analyzed to explore factors associated with positive screening for TB, including being exposed to HIV and current HIV status. Results: Five percent (55/1100) screened reported a close TB contact and 21% (n=231) had positive TB symptom screen. History of close TB contact was a risk factor for positive screening for TB symptoms (OR 1.89 CI 1.05-3.4) while being HIV negative was protective (OR 0.3, Cl 0.19-0.62). HIV exposure was associated with increased risk of TB exposure (OR 2.9 CI 1.61-5.19). Conclusion: Integrating HIV variables in the existing WHO screening tool for childhood TB can be useful in early detec- tion and treatment of TB in HIV exposed children in resource limited settings. Keywords: Childhood TB screening; HIV Exposure screening; TB/HIV integration.