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In preparation of an ongoing trial to improve the treatment of leprosy (MetLep, clinicaltrials.gov: NCT05243654), we conducted a photovoice project among persons affected by leprosy in eastern Indonesia. Photovoice is a participatory visual method in which photographic images are used to explore community health and social issues among disadvantaged populations. This project generated opportunities to visualize stigma and misunderstandings people with leprosy face, and the social and mental burden that this puts on them and those around them.

Plasma viral load (VL) and CD4(+) T cell count are widely used as biomarkers of HIV type 1 (HIV-1) replication, pathogenesis, and response to antiretroviral therapy (ART). However, the clinical potential of cell-associated (CA) HIV-1 molecular markers is much less understood. Here, we measured CA HIV-1 RNA and DNA in HIV-infected individuals treated with temporary ART initiated during primary HIV-1 infection. We demonstrate substantial predictive value of CA RNA for (a) the virological and immunological response to early ART, (b) the magnitude and time to viral rebound after discontinuation of early ART, and (c) disease progression in the absence of treatment. Remarkably, when adjusted for CA RNA, plasma VL no longer appeared as an independent predictor of any clinical endpoint in this cohort. The potential of CA RNA as an HIV-1 clinical marker, in particular as a predictive biomarker of virological control after stopping ART, should be explored in the context of HIV-1 curative interventions.

Skin cancer is an emerging public health issue, and despite many misconceptions, it encompasses all races and ethnicities. Although skin cancer is less common in dark populations than in light-skinned Western societies, it is often diagnosed at a more advanced stage leading to a worse prognosis and overall survival rate. This may be explained by cultural and socioeconomic factors (e.g., lack of knowledge, taboo) and less accessibility to appropriate medical healthcare. The following chapter will focus on the most common skin cancers seen in migrant populations, such as Kaposi’s sarcoma, malignant melanoma, keratinocyte cancers, and primary cutaneous lymphomas.

Podoconiosis is a form of lymphoedema that occurs in tropical highland areas in genetically susceptible individuals who are exposed to irritant volcanic soils. The disease is preventable through consistent use of footwear and attention to foot hygiene; however, in endemic areas there is a strong barefoot tradition, and many cannot afford shoes. Patients with podoconiosis face significant physical disability, psychological comorbidity, reduced quality of life and experience frequent episodes of systemic illness due to acute dermatolymphangioadenitis. This review provides an overview of this important and neglected tropical skin disease and summarizes the latest research findings.

The Primo-SHM trial, a multicenter randomized trial comparing no treatment with 24 or 60 weeks of combination antiretroviral therapy (cART) during primary human immunodeficiency virus (HIV) infection (PHI), recently demonstrated that temporary early cART lowered the viral set point and deferred the need for re-initiation of cART during chronic HIV infection. This study examined whether the beneficial effect of early treatment was caused by preservation of immunological responses. Twenty-seven treated and 20 untreated PHI individuals participating in the Primo-SHM trial were compared at viral set point, that is, 36 weeks after baseline or after treatment interruption, respectively, for a diverse set of immunological parameters. The results show no differences between treated and untreated individuals at the level of effector T-cell formation or replication capacity of the T-cells; regulation of various T, B, natural killer, or dendritic cells; polyfunctionality of the CD8 T-cells; preservation of CD4 T-cells in the gut associated lymphoid tissue; or immune activation. There were subtle differences in the quality of the cytolytic CD4 T-cell response: 11% (median) of CD4 T-cells of the early treated individuals produced the cytolytic molecule perforin compared to 5% in untreated individuals (p=0.046), and treatment caused a modest increase in CD4 T-cells expressing both perforin and granzyme B (median 9% vs. 4% of CD4 T-cells; p=0.045). Early treatment had a modest positive effect on the quality of the CD4 T-cell response. It remains unclear, however, whether these subtle immunological differences were the cause or a result of the lower viral set point in patients who received early treatment.

Contains fulltext : 175954.pdf (Publisher’s version ) (Open Access) To our knowledge, this is the first case report of juvenile dermatomyositis (JDM) in Tanzania. It demonstrates that the characteristic cutaneous findings of JDM may easily be overlooked, especially on dark skin, and the difficulty of clinical management in resource-constrained settings.

A high prevalence of low bone mineral density (BMD) has been reported among men with primary or chronic human immunodeficiency virus (HIV) infection. To gain further insight into the contribution of HIV infection, we compared the BMD of 41 men who have sex with men (MSM) with primary HIV infection, 106 MSM with chronic HIV infection, and a control group of 30 MSM without HIV infection. Low BMD, defined as a z score of ≥2.0 SDs below the mean at the lumbar spine or hip, was highly prevalent in all 3 groups. In the multivariate analyses, HIV infection was not associated with BMD, suggesting that low BMD previously reported in HIV-infected MSM may predate HIV acquisition. © 2012 The Author.

Background Neutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the memory B cell compartment following 6 months of cART or in the absence of treatment. The patients included participated in the Primo-SHM trial where patients with an early HIV-1 infection were randomized to no treatment or treatment for 24 or 60 weeks. Methods Primo-SHM trial patients selected for the present study were untreated (n = 23) or treated for 24 weeks (n = 24). Here we investigate memory B cell properties at viral set-point and at a late time point (respectively median 54 and 73 weeks) before (re)-initiation of treatment. Results At viral set-point, the memory B cell compartment in treated patients demonstrated significantly lower fractions of antigen-primed, activated, memory B cells (p = 0.006). In contrast to untreated patients, in treated patients the humoral HIV-specific response reached a set point over time. At a transcriptional level, sets of genes that showed enhanced expression in memory B cells at viral setpoint in untreated patients, conversely showed rapid increase of expression of the same genes in treated patients at the late time point. Conclusion These data suggest that, although the memory B cell compartment is phenotypically preserved until viral setpoint after treatment interruption, the development of the HIV-specific antibody response may benefit from exposure to HIV. The effect of viral exposure on B cell properties is also reflected by longitudinal changes in transcriptional profile in memory B cells over time in early treated patients.

Objectives The aim of the study was to compare health-related quality of life (HRQL) over 96 weeks in patients receiving no treatment or 24 or 60 weeks of combination antiretroviral therapy (cART) during primary HIV-1 infection (PHI). Methods A multicentre prospective cohort study of PHI patients, with an embedded randomized trial, was carried out. HRQL was assessed with the Medical Outcomes Study Health Survey for HIV (MOS-HIV) and a symptom checklist administered at weeks 0, 8, 24, 36, 48, 60, 72, 84 and 96. Mixed linear models were used for the analysis of differences in HRQL among the three groups. Results A total of 112 patients were included in the study: 28 received no treatment, 45 received 24 weeks of cART and 39 received 60 weeks of cART. Over 96 weeks of follow-up, the groups receiving 24 and 60 weeks of cART had better cognitive functioning than the no-treatment group (P = 0.005). Patients receiving 60 weeks of cART had less pain (P = 0.004), better role functioning (P = 0.001), better physical functioning (P = 0.02) and a better physical health summary score (P = 0.006) than the groups receiving no treatment or 24 weeks of cART. Mental health was better in patients receiving 24 weeks of cART than in patients in the no-treatment group or the group receiving 60 weeks of cART (P = 0.02). At week 8, patients in the groups receiving 24 and 60 weeks of cART reported more nausea (P = 0.002), diarrhoea (P

BACKGROUND In vitro, animal, and mathematical models suggest that human immunodeficiency virus (HIV) co- or superinfection would result in increased fitness of the pathogen and, possibly, increased virulence. However, in patients, the impact of dual HIV type 1 (HIV-1) infection on disease progression is unclear, because parameters relevant for disease progression have not been strictly analyzed. The objective of the present study is to analyze the effect of dual HIV-1 infections on disease progression in a well-defined cohort of men who have sex with men. METHODS Between 2000 and 2009, 37 men who had primary infection with HIV-1 subtype B, no indication for immediate need of combination antiretroviral therapy (cART), and sufficient follow-up were characterized with regard to dual infection or single infection and to coreceptor use. Patients were followed to estimate the effect of these parameters on clinical disease progression, as defined by the rate of CD4(+) T-cell decline and the time to initiation of cART. RESULTS Four patients presented with HIV-1 coinfection; 6 patients acquired HIV-1 superinfection, on average 8.5 months from their primary infection; and 27 patients remained infected with a single strain. Slopes of longitudinal CD4(+) T-cell counts and time-weighted changes from baseline were significantly steeper for patients with dual infection compared with patients with single infection. Multivariate analysis showed that the most important parameter associated with CD4(+) T-cell decline over time was dual infection (P = .001). Additionally, patients with HIV-1 coinfection had a significantly earlier start of cART (P

For the development of a neutralizing antibody-based human immunodeficiency virus type 1 (HIV-1) vaccine, it is important to characterize which antibody specificities are most effective against currently circulating HIV-1 variants. We recently reported that HIV-1 has become more resistant to antibody neutralization over the course of the epidemic, and we here explore whether this increased neutralization resistance is also observed for the newly identified broadly neutralizing antibodies (BrNAbs) PG9, PG16, and VRC01. Furthermore, we performed a comprehensive analysis of the neutralizing sensitivity of currently circulating recently transmitted subtype B viruses to the currently most known BrNAbs. Virus variants isolated less than 6 months after seroconversion from individuals who seroconverted between 2003 and 2006 ( n = 21) were significantly more resistant to neutralization by VRC01 than viruses from individuals who seroconverted between 1985 and 1989 ( n = 14). In addition, viruses from contemporary seroconverters tended to be more resistant to neutralization by PG16, which coincided with the presence of more mutations at positions in the viral envelope that may potentially influence neutralization by this antibody. Despite this increased neutralization resistance, all recently transmitted viruses from contemporary seroconverters were sensitive to at least one BrNAb at concentrations of ≤5 μg/ml, with PG9, PG16, and VRC01 showing the greatest breadth of neutralization at lower concentrations. These results suggest that a vaccine capable of eliciting multiple BrNAb specificities will be necessary for protection of the population against HIV-1 infection.

By comparing HIV-1 variants from people who became infected at the beginning of the epidemic and from people who have recently contracted the virus, we observed an enhanced resistance of the virus to antibody neutralization over time, accompanied by an increase in the length of the variable loops and in the number of potential N-linked glycosylation sites on the HIV-1 envelope gp120 subunit. The enhanced neutralization resistance of HIV-1 in contemporary seroconverters coincided with the poorer elicitation of neutralizing antibody responses, which may have implications for vaccine design.

Background We assessed whether quadruple or triple-class therapy for the initial treatment of HIV-1 infection provides a virological benefit over standard triple therapy in patients with very high plasma viraemia. The assessment was made based on a national observational HIV cohort in the Netherlands. Methods Inclusion criteria were age ≥18 years, treatment-naive, plasma viral load (pVL) ≥500,000 copies/ml and initiation of quadruple or triple therapy between 2001 and 2011. Time to viral suppression, defined as pVLResults A total of 675 patients were included: 125 (19%) initiated quadruple and 550 (81%) triple therapy. Median pVL was 5.9 (IQR 5.8–6.1) log10 copies/ml in both groups ( P=0.49). 22 (18%) patients on quadruple and 63 (12%) on triple therapy interrupted the treatment regimen because of drug-related toxicity ( P=0.06). Median time to viral suppression was 5.8 (IQR 4.6–7.9) and 6.0 (4.0–9.4) months in the patients on quadruple and triple therapy, respectively (log-rank, P=0.42). In the adjusted Cox analysis, quadruple therapy was not associated with time to viral suppression (HR 1.07 [95% CI 0.86, 1.33], P=0.53). Similar results were seen when comparing triple- versus dual-class therapy ( n=72 versus n=601, respectively). Conclusions Initial quadruple- or triple-class therapy was equally effective as standard triple therapy in the suppression of HIV-1 in treatment-naive patients with very high viraemia and did not result in faster pVL decreases, but did expose patients to additional toxicity.

The dynamics of immune cell populations during acute HIV-1 infection are not fully deciphered, especially for non-T cells. In this study, we tested whether specific cellular subsets of the innate arm of the immune response are affected early after HIV-1 infection. Using a cohort of HIV-1-infected individuals, we have monitored the relative frequency of blood T lymphocytes, monocytes, and DCs at various infection stages and measured their respective intracellular HIV-1 DNA loads. The HIV-1 DNA load in naive CD4+ T lymphocytes, which are lost very early during acute infection, was ten- to 100-fold lower than in CD57– and CD57+ memory CD4+ T lymphocytes. We observed that despite rapid, persistent loss after HIV-1 infection, pDCs represented a non-negligible HIV-1 DNA reservoir. CD16+ proinflammatory cDCs and monocytes accumulated gradually, and HIV-infected CD16+ monocytes contained higher HIV-1 DNA loads than their CD16– counterpart during acute infection. During chronic infection, CD16+ cDCs exhibited higher HIV-1 DNA loads than the CD16– population. Overall, our results demonstrate that non-T cell compartments are a major HIV-1 DNA reservoir, and CD16+ monocytes and CD16+ cDCs potentially play an important role in HIV-1 dissemination.

Objective: To assess the bone mineral density (BMD) in a cohort of men with primary HIV-1 infection (PHI). Methods: Thirty-three men with PHI had a dual-energy X-ray absorptiometry (DXA) of the lumbar spine, femoral neck and total hip. Osteopenia and osteoporosis were defined according to WHO criteria as T-scores between -1 and -2.5 and -2.5 or less, respectively. The association between clinical and laboratory parameters and BMD was investigated using multivariable linear regression analysis. Results: Mean age was 38 (SD 9) years and mean body mass index (BMI) 22.7 (SD 3.3) kg/m(2). Twenty-four men (73%) had a negative or indeterminate Western blot, 32 men (97%) were combination antiretroviral therapy-naive. Mean plasma HIV-1 RNA was 5.0 (SD 1.2) log(10) copies/ml. Mean lumbar spine T (-0.8, SD 1.3, P = 0.001) and Z-scores (-0.7, SD 1.3, P = 0.004) and femoral neck T-score (-0.5, SD 0.9, P = 0.003) were significantly lower compared to the reference population. 15/33 men (45%) had osteopenia and 2/33 (6%) osteoporosis. Markers of bone turnover did not differ between patients with or without osteopenia/osteoporosis. Age was negatively associated with femoral neck (beta-coefficient = -0.05, P