Increased CD4 counts, pain and depression are correlates of lower sleep quality in treated HIV positive patients with low baseline CD4 counts.

Poor sleep quality leads to increased immune activation and immune activation leads to worse sleep quality. South African HIV positive patients typically have delayed start of treatment, which has been associated with CD4+ effector T cells being more spontaneously activated in chronically treated patients. This cross-sectional study investigated whether subjective sleep quality was associated with CD4+ T lymphocyte reconstitution in treated South African HIV+ patients. One hundred and thirty-nine treated HIV+ patients (109 F, age average (SD) = 43 (9)) were recruited from Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, South Africa. Participants completed questionnaires evaluating their subjective sleep quality (Pittsburgh Sleep Quality Index), daytime sleepiness (Epworth sleepiness scale), pain, and depression severity (Beck Depression Inventory). Univariate and multivariate analyses were run to determine the correlates of sleep quality in this population. Patients had been on antiretroviral treatment for about 4 years and had increased their CD4 counts from a median at baseline of 82 to 467 cells/µL. They had overall poor sleep quality (average (SD) PSQI = 7.7 (±5), 61% reporting PSQI > 5, a marker of lower sleep quality), 41% had clinical depression (average (SD) BDI = 17 (±12)) and 55% reported pain. In two separate multivariate analyses, both the overall CD4 count increase from baseline (p = 0.0006) and higher current CD4 counts (p = 0.0007) were associated with worse sleep quality, when adjusting for depression severity (p < 0.001), daytime sleepiness (p = 0.01) and the presence of pain (p < 0.01). In this cohort of treated South African HIV positive patients, poor sleep quality was associated with higher current CD4 counts, when adjusting for depression severity, daytime sleepiness and pain. Further studies should investigate the temporal relationship between HIV-related poor sleep quality and underlying immune activation.

Treatment outcomes of pre- and extensively drug-resistant tuberculosis in Johannesburg, South Africa.

BACKGROUND: Extensively drug-resistant tuberculosis (XDR-TB) has a poor treatment success rate and high mortality. Multidrug-resistant TB (MDR-TB) has worse outcomes when there is added resistance to second-line injectable drugs (pre-XDR-TBSLID) or fluoroquinolones (pre-XDR-TBFQ). OBJECTIVES: Treatment outcomes in patients with pre-XDR-TB and XDR-TB in a high HIV prevalence area were compared. METHODS: A retrospective medical record review was conducted of patients with pulmonary pre-XDR-TB and XDR-TB managed from 2008 to 2010 at Sizwe Tropical Disease Hospital, Johannesburg, South Africa. Standardised MDR-TB treatment was instituted and was subsequently individualised when further second-line susceptibility results became available. RESULTS: Of 86 patients studied, 95% were sputum smear-positive at baseline, 73% had sputum culture conversion, and 65% were human immunodeficiency virus (HIV) infected, with a median CD4 count of 201 cells/mm³. Of 53 patients with XDR-TB, 26 with pre-XDR-TBFQ and 7 with pre-XDR-TBSLID, respectively 13%, 12% and 29% were cured, 21%, 23% and 57% had a favourable outcome, and 26%, 23% and 14% died. Clofazimine (P < 0.001) and linezolid (P = 0.044) impacted on favourable outcomes. CONCLUSION: Patients with pre-XDR-TBFQ did not have better outcomes than those with XDR-TB. In countries with standardised regimens for resistant TB, patients with pre-XDR-TBFQ may need to receive XDR-TB treatment.

Evaluation of screening and treatment of cryptococcal antigenaemia among HIV-infected persons in Soweto, South Africa.

OBJECTIVES: We retrospectively evaluated clinic-based screening to determine the prevalence of cryptococcal antigenaemia and management and outcome of patients with antigenaemia. METHODS: Cryptococcal antigen (CrAg) screening of HIV-infected adults who attended the HIV clinic at Chris Hani Baragwanath Hospital was conducted over 19 months. Data collected from CrAg-positive patients included CD4 T-lymphocyte count at screening, prior or subsequent cryptococcal meningitis (CM), antifungal and antiretroviral treatment and outcome after at least 8 months. RESULTS: Of 1460 patients with no prior CM, 30 (2.1%) had a positive CrAg test. The prevalence of antigenaemia among patients with a CD4 count < 100 cells/µl and no prior CM was 2.8% (20 of 708). Of 29 evaluable CrAg-positive patients with no prior CM, 14 (48%) did not return for post-screening follow-up. Of these 14, five developed CM and one (7%) was known to be alive at follow-up. Of 15 patients who returned for follow-up, two already had evidence of nonmeningeal cryptococcosis. Overall, 11 received fluconazole, one did not and fluconazole treatment was unknown for three. Among these 15, one developed CM and 10 (67%) were known to be alive at follow-up. Overall, 18 (62%) of 29 CrAg-positive patients died or were lost to follow-up. Seven (0.5%) of 1430 CrAg-negative patients developed CM a median of 83 days post-screening (range 34 to 219 days). CONCLUSIONS: Loss to follow-up is the major operational issue relevant to scale-up of screen-and-treat. Patient outcomes may be improved by rapid access to CrAg results and focus on linkage to and retention in HIV care.

Tuberculosis in older adults in Soweto, South Africa.

The impact of tuberculosis (TB) on older adults in Southern Africa is rarely emphasised. The case notification rate in 2004 among the elderly in Soweto was 262 per 100 000 population. The elderly comprised 5.8% of adults and 1.6% of adults notified. Among 110 elderly patients studied, 50% had pulmonary TB, 37% had extra-pulmonary TB (EPTB) and 13% had both. A predisposing disease occurred in 46%. TB was microbiologically proven in 77%. Human immunodeficiency virus (HIV) status was known for 25 (23%) patients, with 10 (9% of the cohort) being HIV-infected. HIV-infected adults had more EPTB, anaemia and hyponatraemia. Older adults in Soweto bear a high burden of TB.

Efavirenz-based combination antiretroviral therapy after peripartum single-dose nevirapine.

Single-dose nevirapine (sdNVP) reduces mother-to-child HIV transmission, but induces NVP resistance and subsequent NVP-based combination antiretroviral therapy (cART) may fail. Some resistance mutations affect NVP more than efavirenz (EFV). We evaluated virological suppression of EFV-based cART in women after sdNVP. A retrospective analysis matched 107 women who had received sdNVP within the 24 months before cART (cases) with women who had never received sdNVP (controls). By total cohort (intention-to-continue treatment) at week 96, 65% of cases and 73% of controls had a viral load (VL) <400 copies/mL and 63% of cases and 64% of controls had VL <25 copies/mL. At weeks 48 and 96, women starting cART less than six months after sdNVP (n = 20) had VL <400 copies/mL of 90% and 75%, respectively compared with 90% and 70%, respectively, for controls. Overall 172 (80%) women reached week 96. EFV-based cART, in field conditions, was effective for women after sdNVP, even within six months of sdNVP.

Immune reconstitution inflammatory syndrome involving the skin.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) occurs in 10-25% of unselected patients starting highly active antiretroviral therapy (HAART). About 52-78% of these cases involve cutaneous features. AIM: To describe the prevalence and incidence of new dermatological conditions within 6 months of patients starting HAART, and to specify the clinical and immunological features and time of onset in patients responding to HAART. METHODS: A retrospective cohort analysis was performed of 59 treatment-naive patients started on HAART and followed up for 6 months by a clinician trained in dermatology. Medical records were reviewed for new dermatological conditions diagnosed clinically. RESULTS: In all, 30 patients (50.8%) developed 45 new skin conditions at a median of 8 weeks (range 3-24 weeks) after starting HAART. The incidence rate was 104.5 cases per 100 patient-years. Diagnoses included seborrhoeic dermatitis (nine patients), anogenital herpes (seven patients), acne, tinea and folliculitis (six patients each), Kaposi's sarcoma, herpes zoster, genital warts and eczema (two patients each), and molluscum contagiosum, planar warts and pityriasis versicolor (one patient each). Significantly more women (23/38; 60.5%) than men (7/21; 33.3%) (P < 0.05) developed new skin lesions after starting HAART. Baseline median CD4 counts in those with and without IRIS were 60/microL and 62/microL, respectively, and in both groups, the counts increased to > 90/microL by week 12. Baseline median viral load was > 100,000 copies/mL and was < or = 32 copies/mL by week 12. In both groups, the majority of patients were in World Health Organization stages 3 and 4. CONCLUSIONS: New skin lesions were very common in this cohort, with the majority being women and patients with very low baseline CD4 counts.

Influenza- and respiratory syncytial virus-associated adult mortality in Soweto.

BACKGROUND: Influenza and respiratory syncytial virus (RSV) infections cause seasonal excess mortality and hospitalisation in adults (particularly the elderly) in high-income countries. Little information exists on the impact of these infections on adults in Africa. OBJECTIVES: To estimate influenza- and RSV-related adult mortality, stratified by age and hospitalisation in Soweto. STUDY DESIGN: A retrospective hospital-based study in Soweto from 1997 to 1999 to estimate influenza- and RSV-related excess all-cause deaths and hospitalisation using a rate-difference method. The study was based on influenza seasons of varying severity, provided by surveillance data. RESULTS: Influenza seasons were significantly associated with excess mortality in adults across all 3 years, except for 18 - 64-year-olds in 1998. Excess mortality was highest in those > or = 65 years of age: 82.8/100 000 population in the mild 1997 season and 220.9/100 000 in the severe 1998 season. Influenza significantly increased adult medical hospitalisation in the severe 1998 season alone. RSV did not significantly affect mortality or hospitalisation. CONCLUSION: Influenza-related mortality was substantial and disproportionately affected the elderly. Influenza vaccination for the elderly warrants consideration. The RSV-related burden was not significantly increased but merits observation over a longer period.

Shigella bacteraemia over a decade in Soweto, South Africa.

Shigella infection rarely penetrates beyond the intestinal mucosa to cause bacteraemia. AIDS patients may be at increased risk. We investigated Shigella bacteraemia rates over a decade in a South African population with a high HIV prevalence and analysed presentation and outcome. A retrospective cohort analysis was performed for hospitalized patients for 2003-2006. The rates were compared to those for 1996-1998. Adult medical rates decreased from 0.195/1000 in 1996-1998 to 0.087/1000 admissions in 2003-2006, and paediatric rates were 0.807/1000 and 0.809/1000 admissions, respectively. Twenty patients were children (median age 7 months) and 14 were adults (median age 41 years). The main clinical presentations were acute (

A high incidence of lactic acidosis and symptomatic hyperlactatemia in women receiving highly active antiretroviral therapy in Soweto, South Africa.

BACKGROUND: Lactic acidosis and symptomatic hyperlactatemia may complicate nucleoside reverse-transcriptase inhibitor use. Females may be at increased risk for such complications. Our study evaluated the incidence of lactic acidosis and symptomatic hyperlactatemia by sex, analyzed clinical features, and described the safety of reintroducing highly active antiretroviral therapy (HAART) with zidovudine replacing stavudine. METHODS: A retrospective cohort analysis was performed for 1735 adults (63% of whom were female) who initiated HAART from April 2004 through August 2005 in Soweto, South Africa, with follow-up until February 2006. Patients with lactate levels > or =4.5 mmol/L and no potential cause of elevated lactic acidosis other than receipt of HAART were included in the study. RESULTS: A total of 23 patients (22 of whom were female) experienced lactic acidosis. The overall incidence was 10.6 cases per 1000 patient-years; the incidence was 16.1 cases per 1000 patient-years in female patients and 1.2 cases per 1000 patient-years in male patients. Seven (30.4%) of the patients died. Eight (34.8%) of the patients were obese (body mass index [calculated as weight in kilograms divided by the square of height in meters], >30) at HAART initiation. Forty-four patients (37 of whom were female) had symptomatic hyperlactatemia. The overall incidence was 20.2 cases per 1000 patient-years, with an incidence of 27.0 cases per 1000 patient-years in female patients and 8.7 cases per 1000 patient-years in male patients. None of the patients died. Nine (20.4%) of the patients were obese at HAART initiation. Sixty-six of 67 patients were receiving stavudine, and 5 patients were receiving didanosine. Among 56 patients who restarted HAART with zidovudine for a cumulative nucleoside reverse-transcriptase inhibitor reexposure of 44.6 patient-years--including 41 patients who received treatment for > or =9 months--there were no relapses. CONCLUSION: Women in Soweto, South Africa, have a higher frequency of symptomatic hyperlactatemia and lactic acidosis than has been reported for patients in other study groups. In cases associated with stavudine use, restarting HAART with zidovudine seemed to be safe and effective for patients with limited nucleoside reverse-transcriptase inhibitor alternatives.

Adherence to antiretroviral therapy in HIV-infected adults in Soweto, South Africa.

Little is known about achievable levels of antiretroviral treatment (ART) adherence in resource-limited settings. We conducted a cross-sectional study of adherence among patients at Chris Hani Baragwanath Hospital's Adult HIV Clinic in Soweto, South Africa. Adherence was assessed using a 1-month, self-report questionnaire and was calculated as a ratio of doses taken to doses prescribed. The 66 patients studied had a mean age of 36.1 years, a median duration of ART use of 18 months, and an overall baseline median CD4(+) cell count of 200/mm(3) (IQR: 114-364). The adherence reported by these patients for the previous month was >95% for 58 patients (88%), 90-95% for 6 (9%) and, < 90% for 2 (3%). The main reasons given for missing doses were being away from home (30%), difficulty with the dosing schedules (23%), and running out of pills (12%). Adherence decreased considerably with fear of being stigmatized by the sexual partner (OR = 0.13 95%, CI 0.02-0.70). Plasma HIV RNA levels were <400 copies/ml in the majority of patients (73% of those with adherence >95% and 88% of patients with < or =95% adherence) and the overall median CD4(+) cell count rose to 324/mm(3) (IQR: 193-510). High adherence and viral suppression are achievable for a significant proportion of HIV-infected patients taking ART in a resource-limited area such as Soweto, South Africa. Strategies to maximize adherence in this setting should emphasize ready access to affordable and simple ART regimens, as well as HIV education programs to help increase awareness and decrease disease stigmatization.

Cryptococcal meningitis caused by Cryptococcus neoformans var. gattii, serotype C, in AIDS patients in Soweto, South Africa.

We present four patients from South Africa with meningitis caused by Cryptococcus neoformans var. gattii, serotype C. These are the first patients with human immunodeficiency virus (HIV) infection to be reported with serotype C meningitis.

Prevalence and clinical manifestations of disseminated Mycobacterium avium complex infection in South Africans with acquired immunodeficiency syndrome.

In a sample of 100 hospitalized human immunodeficiency virus-seropositive black South African patients with CD4 cell counts of <100 cells/mm(3), the point prevalence of disseminated Mycobacterium avium complex infection was 10%, in contrast with other African studies that report that the infection is uncommon. The point prevalence of Mycobacterium tuberculosis was 54%. The clinical and laboratory features of these patients were largely unhelpful in detecting M. avium complex; the BACTEC blood culture (Becton Dickinson) was the only reliable method.

Pneumococcal bacteremia in adults in Soweto, South Africa, during the course of a decade.

We retrospectively reviewed 414 episodes of pneumococcal bacteremia that occurred in adults from July 1986 through June 1987 (1986/1987) and from July 1996 through June 1997 (1996/1997) to monitor the incidence and clinical and laboratory characteristics and to assess the influence of human immunodeficiency virus (HIV) infection on any changes. The incidence increased from 26 per 100,000 persons in 1986/1987 to 36 per 100,000 persons in 1996/1997; the increase was most marked among patients who were aged 25-44 years (24 cases per 100,000 persons to 45 per cases 100,000 persons) and > or =65 years (43 cases per 100,000 persons to 50 cases per 100,000 persons). Of 161 patients who were tested for HIV in 1996/1997, 108 (67%) were HIV seropositive. Among the general population, the prevalence of other underlying diseases and smoking decreased from 45% and 67%, respectively, in 1986/1987 to 23% (P<.0001) and 35% (P<.0001) in 1996/1997. Strains of pneumococci that were not susceptible to penicillin were found in 4% patients in 1986/1987 and 12% in 1996/1997 (P=.005). This increase occurred exclusively among the HIV-infected patients (22% of the HIV-seropositive patients versus 4% of HIV-seronegative patients; P=.008), and there was a parallel increase for childhood serotypes (51% of HIV-seropositive patients versus 17% of HIV-seronegative patients; P<.0001).

Occupational exposure of interns to blood in an area of high HIV seroprevalence.

OBJECTIVE: To determine the epidemiology of work-related exposure to blood among interns. DESIGN: Interns were invited to complete anonymously a questionnaire concerning their past percutaneous and mucocutaneous exposures to blood. SETTING: Chris Hani Baragwanath Hospital, Soweto, and Johannesburg Hospital, Gauteng, where HIV infection is common among patients. RESULTS: Ninety-eight interns (96%) were surveyed. Sixty-nine per cent of interns reported one or more percutaneous exposures to blood during the intern year, and 33% of interns recalled accidental percutaneous exposure to HIV-infected blood. Forty-five per cent recalled a mucocutaneous exposure to HIV-positive blood. Only 28 (64%) of 44 percutaneous injuries from HIV-infected patients were reported. During their student clinical training, 56% of interns had suffered a penetrating injury, and 18% recollected needlestick injuries involving HIV-infected patients. The most common mechanisms of injury included unexpected patient movement (23%), needle recapping (17%), and withdrawal of the needle (17%). Half of the injuries occurred during the first 4 months of internship. Only 22% of intern percutaneous exposures could have been avoided by following universal precautions. CONCLUSIONS: Intern and medical student exposure to blood is extremely common, but is markedly underreported. Strict compliance with universal precautions will not prevent the majority of exposures. Priorities should be the introduction of safer techniques and equipment, skills training and methods of reporting blood exposures.

The utility of bone-marrow examination in HIV-infected adults in South Africa.

We retrospectively reviewed a consecutive case series of 257 adults with HIV infection who had undergone a bone-marrow examination with trephine bone biopsy, to assess the diagnostic usefulness of bone-marrow examination and evaluate possible predictors of a diagnostic examination. Bone-marrow examination was positive in 97 (38%) patients and gave a unique diagnosis in 61 (24%). The diseases were tuberculosis (83 patients), Mycobacterium avium complex infection and cryptococcosis (four patients each), and haematological malignancies (eight patients). The yield of the examination was significantly increased, by univariate analysis, in patients with wasting, oral thrush, leukopenia, CD4< or =100/mm3, and granuloma formation on histopathology. Granulomata were present in 113 (44%) patients, of whom 28 (25%) had no specific cause identified. Granulomata occurred in 22 (25%) of 89 patients with CD4 >100/mm3 compared to 36 (51%) of 70 patients with CD4< or =100/mm3 (OR 0.3; 95%CI 0.15-0.62). Of 48 patients with CD4 <50/mm3, 25 had granulomata, including 15 with caseation necrosis. The yield of bone-marrow examination was considerable in our setting. Expanding access to modern blood culture techniques for mycobacteria to primary care level could limit the number of bone-marrow examinations required.

Bone marrow cryptococcal infection in the acquired immunodeficiency syndrome.

OBJECTIVES: To describe the bone marrow lesions in eight cases of Cryptococcus neoformans infection involving the bone marrow in HIV-infected patients. METHODS: Archival bone marrow biopsies from patients with HIV-related cryptococcosis of the bone marrow were retrospectively reviewed. Cryptocococcal organisms were identified on haematoxylin- and eosin-stained slides and confirmed using mucicarmine staining. RESULTS: Yeast cells stimulated a granulomatous response in all cases despite immunosuppression. The number of cryptococcal organisms appeared to be inversely proportional to the adequacy of the granulomatous response. All patients had a cytopenia. CONCLUSIONS: The ability to mount a tissue response in order to localize organisms is retained in patients with AIDS. Infection of the bone marrow with cryptococci may act in synergy with HIV to cause cytopenia.

Pneumococcal bacteremia during a decade in children in Soweto, South Africa.

OBJECTIVES: To monitor for a decade the incidence and the clinical and microbiologic characteristics of pneumococcal bacteremia in children in Soweto and to assess the influence of HIV infection on any changes. METHODS: Case records of children with pneumococcal bacteremia at Chris Hani Baragwanath Hospital from July, 1986, to June, 1987 (1986/ 1987), and from July, 1996, to June, 1997 (1996/ 1997), were retrospectively reviewed. RESULTS: There were 194 episodes, 62 in 19861 1987 and 132 in 1996/1997. The minimum annual incidence for children younger than 5 years of age increased from 61 per 100000 (179 per 100000 for those <12 months old) in 1986/1987 to 130 per 100000 (349 per 100000 for those <12 months old) in 1996/1997. Sixty-seven (60%) of 111 patients tested in 1996/1997 were HIV-seropositive; none were tested in 1986/1987. The HIV-infected compared with HIV-noninfected were more likely to be malnourished (61% vs. 36%, P = 0.02), less likely to have other underlying disease (12% vs. 50%, P = 0.00001) and more frequently used antibiotics recently (69% vs. 43%, P = 0.008). Penicillin-nonsusceptible isolates were found in 22 (35%) patients in 1986/1987 and 52 (39%) in 1996/1997. There was no significant change in antimicrobial susceptibility during the decade or by HIV serostatus. CONCLUSIONS: Children in Soweto had a high incidence of pneumococcal bacteremia which doubled during the decade mainly as a result of the impact of the HIV epidemic. There has been no significant change in antimicrobial susceptibility for the decade.