The impact of highly active antiretroviral therapy on activities of daily living in HIV-infected adults in South Africa.

This study investigated the relationship between highly active antiretroviral therapy (HAART) and instrumental activities of daily living (IADLs) among two clinical cohorts in South Africa. Between 2003 and 2008 structured questionnaires were administered to HIV-positive patients attending outpatient clinics at an urban hospital (Soweto, n = 3,081) and a rural hospital (Acornhoek, n = 1,247). Among those receiving help, an average of 4.8 and 5.1 h of assistance with IADLs daily was reported (rural and urban participants, respectively), with the patient's mother and children assisting the most. Participants on HAART were 17 and 41% less likely to receive assistance with IADLs in the rural and urban cohorts, respectively, after adjusting for demographic characteristics, healthcare utilization, and CD4 counts. HAART significantly decreased the IADL assistance among patients in South Africa. Alongside clinical benefits, HAART has the potential to reduce the burden of HIV-related care, potentially extending wider social and economic gains to other family members.

Patient referral from nurses to doctors in a nurse-led HIV primary care clinic in South Africa: implications for training and support.

Health services in sub-Saharan Africa are under great pressure to provide adequate clinical care due to the continued HIV epidemic, and nurse-driven models of care are one means to address physician shortages. This case-control study examines the reasons for and correlates of patient referral from nurses to physicians at HIV primary care clinics in South Africa prior to initiating antiretroviral treatment. Ninety-seven HIV-infected cases who required physician consolation and 160 controls who did not require physician consultation (matched on gender, age, and date of clinic visit) were consecutively enrolled at both an urban and rural HIV primary care clinic during a 12-month period beginning in March 2006. Univariate and multivariate logistic regression models were used to assess correlates of patient referral to a physician. Cases were more likely to have lower CD4 cell counts and have WHO Stages III and IV disease compared to controls (p<0.05). Predictors of patient referral were a CD4 cell count between 50 and 200 cells/µl (adj OR: 5.27, 95% CI: 2.16-12.88, p<0.0001), a CD4 cell count below 50 cells/µl (adj OR: 3.47, 95% CI: 1.12-10.78, p=0.032), and Stage IV disease (adj OR: 4.58, 95% CI: 1.35-15.60, p=0.015). Additionally, the following ICD-10 clinical diagnoses were associated with patient referral: tuberculosis, aplastic and other anemias, and lower respiratory tract infection (p<0.05). Nurses can provide adequate clinical and diagnostic management for certain clinical conditions to HIV-infected patients. Further studies are needed to examine specifically how HIV healthcare delivery can be scaled-up in resource-limited settings with a high burden of HIV, but with a minimal healthcare infrastructure.

Integrated Source Case Investigation for Tuberculosis (TB) and HIV in the Caregivers and Household Contacts of Hospitalised Young Children Diagnosed with TB in South Africa: An Observational Study.

BACKGROUND: Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa. METHODS: Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts. RESULTS: Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART. CONCLUSION: In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings-integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed.

Piloting PrePex for Adult and Adolescent Male Circumcision in South Africa--Pain Is an Issue.

BACKGROUND: The World Health Organisation and the Joint United Nations Programme on HIV/AIDS have recommended the scale-up of Medical Male Circumcision (MMC) in countries with high HIV and low MMC prevalence. PrePex device circumcision is proposed as an alternate method for scaling up MMC. OBJECTIVE: Evaluate safety and feasibility of PrePex in South Africa. DESIGN: A multisite prospective cohort PrePex study in adults and adolescents at three MMC clinics. Participants were followed-up 8 times, up to 56 days after PrePex placement. RESULTS: In total, 398 PrePex circumcisions were performed (315 adults and 83 adolescents) their median ages were 26 (IQR: 22-30) and 16 years (IQR: 15-17), respectively. The median time for device placement across both groups was 6 minutes (IQR: 5-9) with the leading PrePex sizes being B (30%) and C (35%) for adults (18-45 years), and A (31%) and B (38%) for adolescents (14-17 years). Additional sizes (size 12-20) were rarely used, even in the younger age group. Pain of device application was minimal but that of removal was severe. However, described pain abated rapidly and almost no pain was reported 1 hour after removal. The Adverse Events rate were experienced by 2.7% (11/398) of all participants, three of which were serious (2 displacements and 1 self-removal requiring prompt surgery). None of the Adverse Events required hospitalization. The majority of participants returned to work within a day of device placement. CONCLUSION: Our study shows that PrePex is a safe MMC method, for males 14 years and above. PrePex circumcision had a similar adverse event rate to that reported for surgical MMC, but device removal caused high levels of pain, which subsided rapidly.

Rates and cost of hospitalization before and after initiation of antiretroviral therapy in urban and rural settings in South Africa.

Few studies have compared hospitalizations before and after antiretroviral therapy (ART) initiation in the same patients. We analyzed the cost of hospitalizations among 3906 adult patients in 2 South African hospitals, 30% of whom initiated ART. Hospitalizations were 50% and 40% more frequent and 1.5 and 2.6 times more costly at a CD4 cell count, 100 cells/mm(3) when compared with 200­350 cells/mm(3) in the pre-ART and ART period, respectively. Mean inpatient cost per patient year was USD 117 (95%confidence interval, 85 to 158) for patients on ART and USD 72(95% confidence interval, 56 to 89) for pre-ART patients. Raising ART eligibility thresholds could avoid the high cost of hospitalization before and immediately after ART initiation.

Increased regression and decreased incidence of human papillomavirus-related cervical lesions among HIV-infected women on HAART.

OBJECTIVE: To determine the impact of HAART on incidence, regression, and progression of cytopathological abnormalities in HIV-infected women. DESIGN: Prospective cohort. METHODS: HIV-infected women (N=1123) from Soweto, South Africa underwent serial cervical smears that were analyzed and reported using the Bethesda System. The results of HAART and non-HAART users were compared using two statistical approaches: a survival analysis assessing risk of incident smear abnormality among women with baseline normal smear results; and analysis with marginal models assessing for an association between HAART use and likelihood of regression/progression in consecutive smears. RESULTS: After multivariate survival analysis, women using HAART with a normal baseline smear were 38% less likely to have an incident smear abnormality during follow-up than nonusers [confidence interval (CI) 0.42-0.91; P=0.01]. Multivariate marginal models analysis identified a significantly increased likelihood (odds ratio 2.61; CI 1.75-3.89; P<0.0001) of regression of cervical lesions among women on HAART. CONCLUSION: Our large prospective cohort study adds significant weight to the side of the balance of clinical research supporting the positive impact of HAART on the natural history of human papillomavirus-related cervical disease in HIV-infected women.

Progression and regression of premalignant cervical lesions in HIV-infected women from Soweto: a prospective cohort.

OBJECTIVE: To ascertain progression and regression of cervical dysplasia in HIV-infected women in Soweto. DESIGN: Prospective cohort. METHODS: Women attending an HIV wellness clinic were offered cervical smears as part of care; smears were assessed using the Bethesda system. Those with high-grade lesions or worse were referred for colposcopy. Progression analyses included women with at least two smears at least 5.5 months apart. Hazard ratios were used to ascertain predictors of progression. RESULTS: Two thousand, three hundred and twenty-five women had a baseline smear; their median age and CD4 cell count was 32 years and 312 cells/µl, respectively; 17% were taking highly active antiretroviral therapy (HAART); 62, 20 and 14% had normal, low-grade squamous intraepithelial lesions (LSIL) or high-grade squamous intraepithelial lesions (HSIL), respectively. Of those with baseline normal or LSIL smears, 1074 had another smear; progression from normal to LSIL was 9.6/100 person-years (95% CI 8.3-11.1) and progression from normal or LSIL to HSIL was 4.6/100 person-years (95% CI 3.9-5.5). Of 225 women with LSIL at baseline and at least one subsequent smear at least 11.5 months later, 44.0% regressed to normal (21.2/100 person-years (95% CI 17.5-25.7)). Multivariate models suggested increasing risk for progression in women with CD4 cell count below 500 cells/µl and HAART may reduce the risk of progression [adjusted hazard ratio (aHR) 0.72 (0.52-0.99)]. CONCLUSION: HIV-infected women have high rates of prevalent and incident HSIL and LSIL with relatively low risk of regression to normal from LSIL. HAART appears to protect against progression. Our findings suggest cervical screening intervals should be less than 10 years - irrespective of age in women with CD4 cell counts below 500 cells/µl.

Body mass index and risk of tuberculosis and death.

BACKGROUND: High BMI has been shown to be protective against tuberculosis (TB) among HIV-uninfected individuals, as well as against disease progression and mortality among those with HIV. We examined the effect of BMI on all-cause mortality and TB incidence among a cohort of HIV-infected adults in Soweto, South Africa. METHODS: A clinical cohort of 3456 HIV-infected adults from South Africa was prospectively followed from 2003 to 2008 with regular monitoring. The primary exposure was BMI and the outcomes of interest were all-cause mortality and a newly diagnosed episode of TB. Cox proportional hazard models assessed associations with risk of mortality or incident TB. RESULTS: Incidence rates of mortality were 10.4/100 person-years for baseline BMI of 18.5 or less, 3.6/100 person-years for baseline BMI 18.6-25, 1.7/100 person-years for baseline BMI 25.1-30, and 1.6/100 person-years for baseline BMI more than 30. Compared to those with normal BMI, overweight and obese participants had a significantly reduced risk of mortality [adjusted hazard ratio 0.59 (95% confidence interval, CI 0.40-0.87) and 0.48 (95% CI 0.29-0.80), respectively]. Incidence rates of TB by baseline BMI were 7.3/100 person-years for underweight, 6.0/100 person-years for normal, 3.2/100 person-years for overweight, and 1.9/100 person-years for obese. Compared to those with normal BMI, those with overweight and obese BMI were at a significantly reduced risk of developing TB [adjusted hazard ratio 0.56 (95% CI 0.38-0.83) and 0.33 (95% CI 0.19-0.55), respectively]. CONCLUSION: HIV-infected individuals with obese and overweight BMI have a significantly reduced risk of both mortality and TB, after adjusting for HAART use and CD4 cell count.