Kate Shearer

Loss to follow-up before and after delivery among women testing HIV positive during pregnancy in Johannesburg, South Africa.

HIV‐positive pregnant women are at heightened risk of becoming lost to follow‐up (LTFU) from HIV care. We examined LTFU before and after delivery among pregnant women newly diagnosed with HIV.

Treatment outcomes after 7 years of public-sector HIV treatment.

Objectives:To assess outcomes over the first 7 years of antiretroviral therapy (ART) at Themba Lethu Clinic, Johannesburg, South Africa. Design:Observational cohort study. Methods:Patients are managed according to South African National Treatment Guidelines. Mortality is ascertained through linkage with the national vital registration system. Loss to follow-up is defined as at least 3 months late for the last scheduled appointment. Results:Between April 2004 and March 2010, 13 227 patients initiated ART, increasing from 1794 in the year 2004/2005 to 2481 in 2009/2010. Median CD4 cell count at ART initiation increased 39% between 2004 and 2009 (82 vs. 114 cells/&mgr;l). The proportion who died within 1 year on ART was below 11% at all time points, whereas the proportion lost by 1 year increased from 8.5% in 2004 to 12.1% in 2009 [risk ratio (RR) 1.42, 95% confidence interval (CI) 1.18–1.71]. We followed the 1794 patients initiated in April 2004 and March 2005 through August 2011 for 8172 person-years. We estimated 25% of patients were lost and 16% died. The overall mortality rate was 3.59 per 100 person-years (95% CI 3.20–4.02). Of the 1577 who completed at least 6 months of follow-up, 213 (13.5%) failed first-line treatment in a median (interquartile range) of 25.9 (15.8–41.4) months on treatment. Of those who failed, 141 (66.2%) switched to second-line for a rate of 48.5 per 100 person-years (95% CI 41.1–57.2). Conclusion:Despite some improvements over 7 years, more intervention is needed in the first year on treatment to reduce overall attrition.

Attrition through multiple stages of pre-treatment and ART HIV care in South Africa.

Introduction While momentum for increasing treatment thresholds is growing, if patients cannot be retained in HIV care from the time of testing positive through long-term adherence to antiretroviral therapy (ART), such strategies may fall short of expected gains. While estimates of retention on ART exist, few cohorts have data on retention from testing positive through long-term ART care. Methods We explored attrition (loss or death) at the Themba Lethu HIV clinic, Johannesburg, South Africa in 3 distinct cohorts enrolled at HIV testing, pre-ART initiation, and ART initiation. Results Between March 2010 and August 2012 we enrolled 380 patients testing HIV+, 206 initiating pre-ART care, and 185 initiating ART. Of the 380 patients enrolled at testing HIV-positive, 38.7% (95%CI: 33.9–43.7%) returned for eligibility staging within ≤3 months of testing. Of the 206 enrolled at pre-ART care, 84.5% (95%CI: 79.0–88.9%) were ART eligible at their first CD4 count. Of those, 87.9% (95%CI: 82.4–92.2%) initiated ART within 6 months. Among patients not ART eligible at their first CD4 count, 50.0% (95%CI: 33.1–66.9%) repeated their CD4 count within one year of the first ineligible CD4. Among the 185 patients in the ART cohort, 22 transferred out and were excluded from further analysis. Of the remaining 163, 81.0% (95%CI: 74.4–86.5%) were retained in care through two years on treatment. Conclusions Our findings from a well-resourced clinic demonstrate continual loss from all stages of HIV care and strategies to reduce attrition from all stages of care are urgently needed.

Costs of inpatient treatment for multi‐drug‐resistant tuberculosis in South Africa

In South Africa, patients with multi‐drug‐resistant tuberculosis (MDR‐TB) are hospitalised from MDR‐TB treatment initiation until culture conversion. Although MDR‐TB accounts for <3% of incident TB in South Africa, 55% of the public sector TB budget is spent on MDR‐TB. To inform new strategies for MDR‐TB management, we estimated the per‐patient cost (USD 2011) of inpatient MDR‐TB treatment.

Predictors of mortality and treatment success during treatment for rifampicin-resistant tuberculosis within the South African National TB Programme, 2009 to 2011: a cohort analysis of the national case register

BACKGROUND The South African Electronic Drug-Resistant Tuberculosis Register (EDRweb) is the national database of registered drug-resistant tuberculosis (DR-TB) cases. METHODS This study was a retrospective, de-identified secondary analysis of EDRweb patients initiating treatment for rifampicin-resistant TB (January 2009 to September 2011). The relative risks of death and treatment success were estimated using modified Poisson regression with robust error estimation. RESULTS Seventeen thousand six hundred and ninety-seven cases of DR-TB were registered and met the inclusion criteria; 52.0% (n=9207) were male and the median age was 35 years (interquartile range 27-43 years). Of the 9419 cases with HIV infection (53.2%), 7157 (76.0%) were on antiretroviral therapy. Most had undergone previous TB treatment (76.5%, n=13531). Multidrug-resistant TB was the most common diagnosis, at 80.6% (n=14272). No treatment outcome was available for 6934 patients (39.2%). For patients with outcomes, 4227 (39.4%) were successfully treated, 2987 (27.8%) died, 2533 (23.7%) were lost to follow-up, and 996 (9.3%) failed. Second-line drug resistance was the strongest predictor of death during DR-TB treatment; extensively drug-resistant TB patients were more likely to have died during treatment (adjusted relative risk 2.63, 95% confidence interval 2.45-2.84). CONCLUSIONS Testing for second-line drug resistance at initiation of DR-TB treatment can identify patients most at risk of treatment failure and death and most in need of individualized treatment.

Increases in regimen durability associated with the introduction of tenofovir at a large public-sector clinic in Johannesburg, South Africa.

In April 2010, tenofovir replaced stavudine in public‐sector first‐line antiretroviral therapy (ART) in South Africa. The association of tenofovir with fewer side effects and toxicities compared to stavudine could translate to increased durability of tenofovir‐based regimens. We evaluated changes over time in regimen durability at the Themba Lethu Clinic, Johannesburg, South Africa.

Incidence and predictors of herpes zoster among antiretroviral therapy-naïve patients initiating HIV treatment in Johannesburg, South Africa

OBJECTIVES To describe the characteristics of HIV-infected patients experiencing herpes zoster after antiretroviral therapy (ART) initiation and to describe the incidence and predictors of a herpes zoster diagnosis. METHODS Adult patients initiating ART from April 2004 to September 2011 at the Themba Lethu Clinic in Johannesburg, South Africa were included. Patients were followed from ART initiation until the date of first herpes zoster diagnosis, or death, transfer, loss to follow-up, or dataset closure. Herpes zoster is described using incidence rates (IR) and predictors of herpes zoster are presented as subdistribution hazard ratios (sHR) and 95% confidence intervals (95% CI). RESULTS Fifteen thousand and twenty-five patients were included; 62% were female, the median age was 36.6 years, and the median baseline CD4 count was 98 cells/mm(3). Three hundred and forty patients (2.3%) experienced herpes zoster in a median of 26.1 weeks after ART initiation. Most (71.5%) occurred within 1 year of initiation, for a 1-year IR of 18.1/1000 person-years. In an adjusted model, patients with low CD4 counts (<50 vs. ≥200 cells/mm(3); sHR: 1.71, 95% CI: 1.21-2.47) and with a prior episode of herpes zoster (sHR: 1.53, 95% CI: 0.97-2.28) were at increased risk of incident herpes zoster. CONCLUSIONS While only 2% of patients were diagnosed with herpes zoster in this cohort, patients with low CD4 counts and those with prior episodes of herpes zoster were at higher risk for a herpes zoster diagnosis.

Impact of choice of NRTI in first-line antiretroviral therapy: a cohort analysis of stavudine vs. tenofovir.

In April 2010, South Africa replaced stavudine with tenofovir in first‐line antiretroviral therapy (ART) despite tenofovirs higher cost. We examined treatment outcomes over 24 months amongst patients initiated on tenofovir‐based vs. stavudine‐based first‐line regimens.

The impact of choice of NNRTI on short-term treatment outcomes among HIV-infected patients prescribed tenofovir and lamivudine in Johannesburg, South Africa.

Introduction Recent WHO guidelines for resource-limited settings recommend tenofovir in first-line antiretroviral therapy (ART) yet there are suggestions that patients receiving nevirapine with tenofovir have worse outcomes than those receiving efavirenz. We sought to compare outcomes among those taking nevirapine vs. efavirenz with tenofovir and lamivudine. Methods We analyzed data on ART naïve, non-pregnant patients, ≥18 years old without tuberculosis co-infection, initiating tenofovir with lamivudine and either nevirapine or efavirenz between April 1, 2010 and July 31, 2011 (when South Africa’s public-sector use of tenofovir began) at Themba Lethu Clinic in South Africa. We measured virologic suppression (viral load <400 copies/ml), virologic failure (2 consecutive viral loads >1000 copies/ml), and attrition (death/loss to follow-up) all at 12 months after ART initiation. Modified Poisson regression with robust error estimation was used to estimate risk ratios (RR) and 95% confidence intervals (CI) for predictors of each outcome. Results 2,254 patients were prescribed efavirenz, 131 nevirapine. Patients were followed a median (range) of 12.0 (0.1–12.0) person-months. 62.2% were female and median (IQR) age was 37.7 years (31.5–44.1). Patients prescribed efavirenz had similar initiating CD4 counts (median 132 for both regimens) but were somewhat more likely to be WHO Stage III or IV (39.6% vs. 33.6%) than those prescribed nevirapine. No difference in attrition was found (aRR: 0.83; 95% CI: 0.49–1.41). Among patients with ≥1 viral load within 1 year on ART, those prescribed nevirapine were as likely to reach virologic suppression (aRR: 0.97; 95% CI: 0.88–1.07) but more likely to experience virologic failure (aRR: 1.84; 95% CI: 1.02–3.31) than those prescribed efavirenz. Conclusions Our results support the notion that, among patients prescribed tenofovir and lamivudine, virologic failure is more common among those taking nevirapine than among those taking efavirenz. Longer-term follow up and larger studies will be needed to confirm this finding.

Marginal structural models to assess delays in second-line HIV treatment initiation in South Africa

Background South African HIV treatment guidelines call for patients who fail first-line antiretroviral therapy (ART) to be switched to second-line ART, yet logistical issues, clinician decisions and patient preferences make delay in switching to second-line likely. We explore the impact of delaying second-line ART after first-line treatment failure on rates of death and virologic failure. Methods We include patients with documented virologic failure on first-line ART from an observational cohort of 9 South African clinics. We explored predictors of delayed second-line switch and used marginal structural models to analyze rates of death following first-line failure by categorical time to switch to second-line. Cox proportional hazards models were used to examine virologic failure on second-line ART among patients who switched to second-line. Results 5895 patients failed first-line ART, and 63% switched to second-line. Among patients who switched, median time to switch was 3.4 months (IQR: 1.1–8.7 months). Longer time to switch was associated with higher CD4 counts, lower viral loads and more missed visits prior to first-line failure. Worse outcomes were associated with delay in second-line switch among patients with a peak CD4 count on first-line treatment ≤100 cells/mm3. Among these patients, marginal structural models showed increased risk of death (adjusted HR for switch in 6–12 months vs. 0–1.5 months = 1.47 (95% CI: 0.94–2.29), and Cox models showed increased rates of second-line virologic failure despite the presence of survivor bias (adjusted HR for switch in 3–6 months vs. 0–1.5 months = 2.13 (95% CI: 1.01–4.47)). Conclusions Even small delays in switch to second-line ART were associated with increased death and second-line failure among patients with low CD4 counts on first-line. There is opportunity for healthcare providers to switch patients to second-line more quickly.