Case 15-2011: A 19-year-old South African woman with headache, fatigue, and vaginal discharge.

No abstract available.This case was presented at the Fourth Annual Workshop on Advanced Clinical Care - AIDS in Durban, South Africa, September 30–October 1, 2010. The workshop was sponsored by the Harvard University Center for AIDS Research, McCord Hospital (Durban), the University of KwaZulu-Natal, the South African HIV Clinicians Society, and the Department of Health of KwaZulu-Natal

Expanding HIV surveillance to include TB patients in resource-limited settings with a generalized epidemic.

Screening of antenatal clinic attendees is central to monitoring the human immunodeficiency virus (HIV) epidemic. However, recent evidence suggests that declining fertility rates are affecting the reliability of antenatal clinic surveys as the epidemic matures. Population-based HIV surveys, while ideal, are resource-intensive, necessitating newer, cost-effective approaches. Unlinked anonymous testing for HIV in sputum of tuberculosis (TB) patients serves as reliable proxy for estimating the burden of symptomatic HIV disease and is a potential adjunct to current surveillance efforts. Unlinked anonymous testing for HIV surveillance in KwaZulu-Natal, South Africa, the epicentre of the global epidemic, is justified, as data from the largest urban TB referral clinic indicate that only 22% of TB patients uptake voluntary HIV testing

Functional characterization of Vif proteins from HIV-1 infected patients with different APOBEC3G haplotypes.

CAPRISA, 2016.Abstract available in PDF file

Changes in natural killer cell activation and function during primary HIV-1 infection.

Background. Recent reports suggest that Natural Killer (NK) cells may modulate pathogenesis of primary HIV-1 infection. However, HIV dysregulates NK-cell responses. We dissected this bi-directional relationship to understand how HIV impacts NK-cell responses during primary HIV-1 infection. Methodology/Principal Findings. Paired samples from 41 high-risk, initially HIV-uninfected CAPRISA004 participants were analysed prior to HIV acquisition, and during viraemic primary HIV-1 infection. At the time of sampling post-infection five women were seronegative, 11 women were serodiscordant, and 25 women were seropositive by HIV-1 rapid immunoassay. Flow cytometry was used to measure NK and T-cell activation, NK-cell receptor expression, cytotoxic and cytokine-secretory functions, and trafficking marker expression (CCR7, α4β7). Non-parametric statistical tests were used. Both NK cells and T-cells were significantly activated following HIV acquisition (p = 0.03 and p<0.0001, respectively), but correlation between NK-cell and T-cell activation was uncoupled following infection (pre-infection r = 0.68;p<0.0001; post-infection, during primary infection r = 0.074;p = 0.09). Nonetheless, during primary infection NK-cell and T-cell activation correlated with HIV viral load (r = 0.32'p = 0.04 and r = 0.35;p = 0.02, respectively). The frequency of Killer Immunoglobulin-like Receptor-expressing (KIRpos) NK cells increased following HIV acquisition (p = 0.006), and KIRpos NK cells were less activated than KIRneg NK cells amongst individuals sampled while seronegative or serodiscordant (p = 0.001;p<0.0001 respectively). During HIV-1 infection, cytotoxic NK cell responses evaluated after IL-2 stimulation alone, or after co-culture with 721 cells, were impaired (p = 0.006 and p = 0.002, respectively). However, NK-cell IFN-y secretory function was not significantly altered. The frequency of CCR7+ NK cells was elevated during primary infection, particularly at early time-points (p<0.0001). Conclusions/Significance. Analyses of immune cells before and after HIV infection revealed an increase in both NK-cell activation and KIR expression, but reduced cytotoxicity during acute infection. The increase in frequency of NK cells able to traffic to lymph nodes following HIV infection suggests that these cells may play a role in events in secondary lymphoid tissue

Impact of blood processing variations on natural killer cell frequency, activation, chemokine receptor expression and function.

Understanding the role of natural killer (NK) cells in human disease pathogenesis is crucial and necessitates study of patient samples directly ex vivo. Manipulation of whole blood by density gradient centrifugation or delays in sample processing due to shipping, however, may lead to artifactual changes in immune response measures. Here, we assessed the impact of density gradient centrifugation and delayed processing of both whole blood and peripheral blood mononuclear cells (PBMC) at multiple timepoints (2–24 h) on flow cytometric measures of NK cell frequency, activation status, chemokine receptor expression, and effector functions. We found that density gradient centrifugation activated the NK cells and modified the chemokine receptor expression. Delays in processing beyond 8 h activated NK cells in PBMC but not in whole blood. Likewise, processing delays decreased chemokine receptor (CCR4 and CCR7) expression in both PBMC and whole blood. Finally, delays in processing PBMC were associated with a decreased ability of NK cells to degranulate (as measured by CD107a expression) or secrete cytokines (IFN-γ and TNF-α). In summary, our findings suggest that density gradient centrifugation and delayed processing of PBMC can alter measures of clinically relevant NK cell characteristics including effector functions; and therefore should be taken into account in designing clinical research studies

Interleukin-10 Promoter Polymorphisms Influence HIV-1 Susceptibility and Primary HIV-1 Pathogenesis.

Interleukin (IL)–10 directly inhibits human immunodeficiency virus type 1 (HIV-1) replication, but it may also promote viral persistence by inactivation of effector immune mechanisms. Here, we show in an African cohort that individuals with genotypes associated with high IL-10 production at 2 promoter single-nucleotide polymorphisms ( 1082 and 592) were less likely to become HIV-1 infected but had significantly higher median plasma viral loads during the acute phase ( 3 months after infection). However, as the infection progressed, the association between genotype and median viral load was reversed. Thus, IL-10 may influence HIV-1 susceptibility and pathogenesis, but effects on the latter may differ according to the infection phase

Evaluation of a synthetic peptide for the detection of anti-Mycobacterium tuberculosis curli pili IgG antibodies in patients with pulmonary tuberculosis.

CAPRISA, 2018.Abstract available in pdf

Association of polymorphisms in the regulatory region of the cyclophilin A gene (PPIA) with gene expression and HIV/AIDS disease progression.

CAPRISA, 2016.Abstract available in PDF file

Interleukin 1-Beta (IL-1β) production by innate cells following TLR stimulation correlates with TB recurrence in art-treated HIV-infected patients.

CAPRISA, 2017.Abstract available

CD8+ T cell breadth and ex vivo virus inhibition capacity distinguish between viremic controllers with and without protective HLA class I alleles.

CAPRISA, 2016.Abstract available in PDF file