A prospective study on the outcome of human immunodeficiency virus-infected patients requiring mechanical ventilation in a high-burden setting.

BACKGROUND: There is a paucity of data on the mortality of patients admitted to the intensive care unit (ICU), despite the fact that human immunodeficiency virus (HIV)-related diseases represent a significant burden to health care resources particularly in sub-Saharan Africa. AIM: To describe the outcome and prognostic factors of HIV-infected patients requiring mechanical ventilation in an ICU. DESIGN: Prospective observational study. METHODS: All 54 patients (34.8 ± 10.4 years, 38 females) admitted with confirmed HIV from October 2012 until May 2013 were enrolled. Disease severity was graded according to APACHEII score. Admission diagnoses, clinical features and laboratory investigations, complications and outcomes were recorded. RESULTS: The mean length of ICU stay was 11.0 days (range: 1-49 days), and 33 patients survived (ICU mortality: 38.9%). The in-hospital mortality at 30 days was 48.1%. ICU mortality was associated with an AIDS-defining diagnosis (OR = 7.97, P = 0.003). Non-survivors had higher APACHEII scores (25.8 vs. 18.6, P = 0.001) and lower mean admission CD4 counts (102.5 vs. 225.2, P = 0.014). Multiple logistical regression analysis confirmed the independent predictive value of WHO stage 4 disease (P = 0.008), lower mean CD4 count on admission (P = 0.057) and higher APACHEII score (P = 0.010) on ICU mortality, and WHO stage 4 (P = 0.007) and higher APACHE II score (P = 0.003) on 30-day mortality. CONCLUSIONS: The ICU mortality of mechanically ventilated HIV-positive patients was high. WHO stage 4 disease and a higher APACHEII score were predictive of both ICU and 30-day mortality, whereas a low CD4 count on admission was associated with ICU mortality.

Novel mutations identified using a comprehensive CCR5-denaturing gradient gel electrophoresis assay.

BACKGROUND: Most mutations detected for the gene for CC chemokine receptor 5 (CCR5) are either relatively specific to different population groups or rarely observed in Africans. OBJECTIVES: To develop a comprehensive mutation detection assay for the entire coding region of CCR5 and to identify novel mutations that may play a role in genetic susceptibility to HIV-1 infection, within the diverse South African population. DESIGN: The study cohort consisted of 103 HIV-seropositive patients and 146 HIV-seronegative controls of predominantly African descent. METHODS: A mutation detection assay for the entire coding region of CCR5 was designed; this included amplification of part of the coding region of CCR2. The assay was based on denaturing gradient gel electrophoresis (DGGE) and allowed the complete analysis of samples from 10 individuals per denaturing gel. RESULTS: The use of the CCR5-DGGE assay led to the identification of seven novel and six previously reported mutations. All novel mutations, including a common polymorphism at codon 35, occurred exclusively in non-Caucasians, indicating possible African origin. CONCLUSION: A comprehensive DGGE mutation detection assay has been developed for the entire coding region of CCR5. Application of this assay resulted in the identification of novel CCR5 mutations, which may have a significant effect on the normal functioning of CCR5 and thus contribute to host variability and susceptibility to HIV-1 infection and/or progression to AIDS within this population.

Impact of timing of antiretroviral therapy initiation on survival of cervical squamous intraepithelial lesions: a cohort analysis from South Africa.

To determine factors that influence excision treatment outcome and recurrence of cervical squamous intraepithelial lesions (SIL) in women living with HIV infection, we analysed 1848 women who underwent excision treatment of cervical SIL at Tygerberg Hospital, Cape Town, South Africa. We compared treatment failure defined as presence of cervical intraepithelial neoplasia (CIN) I (presence of CIN I or higher at first follow-up after excision treatment) and post-excision recurrence of lesions (at one year or later) between women of HIV-positive, -negative or unknown status and examined factors associated with excision treatment outcome and recurrence. HIV-infected women experienced higher treatment failure than uninfected women (53.8% versus 26.9%, P < 0.001). At treatment failure, more HIV-infected women had low-grade squamous intraepithelial lesion (LSIL) compared with uninfected women (64.9% versus 37.3%, P < 0.001). Treatment failure did not differ with the type of excision used in HIV-infected women. HIV-infected women were more likely to experience recurrence of lesions after excision treatment than uninfected women (hazard ratio 1.95, 95% confidence interval [CI] 1.59-2.39; P < 0.001). Antiretroviral therapy (ART) initiated before excision biopsy had a strong protective effect against recurrence (hazard ratio 0.70, 95% CI 0.55-0.89; P = 0.006). Our data suggest that women with cervical SIL initiated on ART earlier may be expected to have better long-term excision treatment outcome. Close follow-up should be maintained after cervical excision treatment, especially in a setting of high HIV prevalence.

Post-traumatic stress disorder among recently diagnosed patients with HIV/AIDS in South Africa.

This study examined the prevalence of and factors associated with post-traumatic stress disorder in recently diagnosed HIV/AIDS patients in South Africa. One hundred and forty-nine (44 male, 105 female) recently diagnosed HIV/AIDS patients (mean duration since diagnosis = 5.8 months, SD = 4.1) were evaluated. Subjects were assessed using the MINI International Neuropsychiatric Interview (MINI), the Carver Brief COPE coping scale and the Sheehan Disability Scale. In addition, previous exposures to trauma and past risk behaviours were assessed. Twenty-two patients (14.8%) met criteria for PTSD. Current psychiatric conditions more likely to be associated with PTSD included major depressive disorder (29% in PTSD patients versus 7% in non-PTSD patients, p = 0.004), suicidality (54% versus 11%, p = 0.001) and social anxiety disorder (40% versus 13%, p = 0.04). Further patients with PTSD reported significantly more work impairment and demonstrated a trend towards higher usage of alcohol as a means of coping. Discriminant function analysis indicated that female gender and a history of sexual violation in the past year were significantly associated with a diagnosis of PTSD. Patients whose PTSD was a direct result of an HIV/AIDS diagnosis (8/22) did not differ from other patients with PTSD on demographic or clinical features. In the South African context, PTSD is not an uncommon disorder in patients with HIV/AIDS. In some cases, PTSD is secondary to the diagnosis of HIV/AIDS but in most cases it is seen after other traumas, with sexual violation and intimate partner violence in women being particularly important.