Ashraf Grimwood

Improved Survival and Antiretroviral Treatment Outcomes in Adults Receiving Community-Based Adherence Support: 5-Year Results From a Multicentre Cohort Study in South Africa

Introduction:A large increase in lay health care workers has occurred in response to shortages of professional health care staff in sub-Saharan African antiretroviral treatment (ART) programs. However, little effectiveness data of the large-scale implementation of these programs is available. We evaluated the effect of a community-based adherence-support (CBAS) program on ART outcomes across 57 South African sites. Methods:CBAS workers provide adherence and psychosocial support for patients and undertake home visits to address household challenges affecting adherence. An observational multicohort study of adults enrolling for ART between 2004 and 2010 was performed. Mortality, loss to follow-up, and virological suppression were compared by intention to treat between patients who received and did not receive CBAS until 5 years of ART, using multiple imputation of missing covariate values. Results:Of the 66,953 patients who were included, 19,668 (29.4%) patients received CBAS and 47,285 (70.6%) patients did not. Complete-case covariate data were available for 54.3% patients. After 5 years, patient retention was 79.1% [95% confidence interval (CI): 77.7% to 80.4%] in CBAS patients versus 73.6% (95% CI: 72.6% to 74.5%) in non-CBAS patients; crude hazard ratio (HR) for attrition was 0.68 (95% CI: 0.65 to 0.72). Mortality and loss to follow-up were independently lower in CBAS patients, adjusted HR (aHR) was 0.65 (95% CI: 0.59 to 0.72) and 0.63 (95% CI: 0.59 to 0.68), respectively. After 6 months of ART, virological suppression was 76.6% (95% CI: 75.8% to 77.5%) in CBAS patients versus 72% (95% CI: 71.3% to 72.5%) in non-CBAS patients (P < 0.0001), adjusted odds ratio was 1.22 (95% CI: 1.14 to 1.30). Improvement in virological suppression occurred progressively for longer durations of ART [adjusted odds ratio was 2.66 (95% CI: 1.61 to 4.40) by 5 years]. Conclusions:Patients receiving CBAS had considerably better ART outcomes. Further scale-up of these programs should be considered in low-income settings.

Improved virological suppression in children on antiretroviral treatment receiving community-based adherence support: A multicentre cohort study from South Africa

Adherence to antiretroviral treatment (ART) is a challenge in childhood, and children on ART have reduced virological suppression compared to adults. This study evaluated the effect of community-based adherence support (CBAS) on virological outcomes amongst children receiving ART in four South African provinces. Patient Advocates are lay CBAS workers who provide adherence and psychosocial support for patients, undertaking home visits to address household challenges affecting adherence. Patient Advocates provide counselling for childrens carers regarding adherence and psychosocial problems. A multicentre cohort study using routinely collected data was conducted at 57 public ART sites including ART-naive children (<16 years) starting ART. Virological suppression until four years of ART was compared between children who received and did not receive CBAS. Analyses were by intention-to-treat, controlling for confounding using multivariable generalised estimating equations. A total of 4853 children were included, of whom 982 (20.2%) received CBAS. The median baseline age was 6.3 years and the baseline CD4 cell percentage was 12.0%; both were equivalent between the two groups. CBAS children had more advanced baseline clinical disease (62.1% vs. 52.6% World Health Organisation stages III or IV; P < 0.0001). A total of 5908 viral load results were analysed. Virological suppression was 65.6% (95% confidence interval [CI]: 62.7–68.4%) vs. 55.5% (95% CI: 54.1–57.0%) in CBAS and non-CBAS children, respectively, at any time-point on treatment (P < 0.0001). In analyses controlling for baseline clinical, demographic, site-related variables and time on ART, children receiving CBAS were more likely to achieve virological suppression, adjusted odds ratio (aOR) 1.60 (95% CI: 1.35–1.89; P < 0.0001). The effect of CBAS increased in magnitude with increasing durations of ART, and CBAS particularly improved virological suppression in a higher-risk subgroup (children younger than two years, aOR 2.47 [95% CI: 1.59–3.84]). CBAS was associated with improved virological suppression in children receiving ART. Expanded implementation of this low-cost intervention should be considered in resource-poor settings.

Progress of preventing mother-to-child transmission of HIV at primary healthcare facilities and district hospitals in three South African provinces

Improving national prevention of mother-to-child (PMTCT) services in South Africa has been challenging. PMTCT outcomes were analysed at 58 primary and secondary level antenatal facilities across seven high HIV-burden sub-districts in three provinces, over an 18 month period during which new South African PMTCT clinical guidelines were implemented and a nurse quality mentor program was expanded. Early infant HIV DNA polymerase chain reaction test positivity reduced by 75.2% from 9.7% (CI: 8.1%-11.5%) to 2.4% (CI: 1.9%-3.1%); p<0.0005. HIV test positivity at 18 months of age decreased by 64.5% from 10.7% (CI: 7.2-15.1%) to 3.8% (CI: 2.4-5.6%); p<0.0005. PMTCT outcomes have improved substantially at these facilities.

Increased vulnerability of rural children on antiretroviral therapy attending public health facilities in South Africa: a retrospective cohort study

BackgroundA large proportion of the 340,000 HIV-positive children in South Africa live in rural areas, yet there is little sub-Saharan data comparing rural paediatric antiretroviral therapy (ART) programme outcomes with urban facilities. We compared clinical, immunological and virological outcomes between children at seven rural and 37 urban facilities across four provinces in South Africa.MethodsWe conducted a retrospective cohort study of routine data of children enrolled on ART between November 2003 and March 2008 in three settings, namely: urban residence and facility attendance (urban group); rural residence and facility attendance (rural group); and rural residents attending urban facilities (rural/urban group). Outcome measures were: death, loss to follow up (LTFU), virological suppression, and changes in CD4 percentage and weight-for-age-z (WAZ) scores. Kaplan-Meier estimates, logrank tests, multivariable Cox regression and generalized estimating equation models were used to compare outcomes between groups.ResultsIn total, 2332 ART-naïve children were included, (1727, 228 and 377 children in the urban, rural and rural/urban groups, respectively). At presentation, rural group children were older (6.7 vs. 5.6 and 5.8 years), had lower CD4 cell percentages (10.0% vs. 12.8% and 12.7%), lower WAZ scores (-2.06 vs. -1.46 and -1.41) and higher proportions with severe underweight (26% vs.15% and 15%) compared with the urban and rural/urban groups, respectively. Mortality was significantly higher in the rural group and LTFU significantly increased in the rural/urban group. After 24 months of ART, mortality probabilities were 3.4% (CI: 2.4-4.8%), 7.7% (CI: 4.5-13.0%) and 3.1% (CI: 1.7-5.6%) p = 0.0137; LTFU probabilities were 11.5% (CI: 9.3-14.0%), 8.8% (CI: 4.5-16.9%) and 16.6% (CI: 12.4-22.6%), p = 0.0028 in the urban, rural and rural/urban groups, respectively. The rural group had an increased adjusted mortality probability, adjusted hazards ratio 2.41 (CI: 1.25-4.67) and the rural/urban group had an increased adjusted LTFU probability, aHR 2.85 (CI: 1.41-5.79). The rural/urban group had a decreased adjusted probability of virological suppression compared with the urban group at any timepoint on treatment, adjusted odds ratio 0.67 (CI: 0.48-0.93).ConclusionsRural HIV-positive children are a vulnerable group, exhibiting delayed access to ART and an increased risk of poor outcomes while on ART. Expansion of rural paediatric ART programmes, with future research exploring improvements to rural health system effectiveness, is required.

Prolonged deferral of antiretroviral therapy in the SAPIT trial: did we need a clinical trial to tell us that this would increase mortality?

Tuberculosis is the major cause of morbidity and mortality in HIV-infected patients in sub-Saharan Africa. HIV infection is often first diagnosed following a diagnosis of tuberculosis, with many patients needing antiretroviral therapy (ART). Starting ART in HIV-infected patients with tuberculosis (TB) may be associated with complications, including side-effects from co-administration of multiple drugs with many overlapping toxicities, reductions in concentrations of certain antiretroviral drugs following the induction of metabolising enzymes and drug transporters by rifampicin, and paradoxical deterioration due to the immune reconstitution inflammatory syndrome (IRIS). Furthermore, the high pill burden of co-treatment could reduce adherence, resulting in poor treatment outcomes for both diseases. These potential harms must be weighed against the high mortality rates in patients with HIV-associated tuberculosis who do not receive ART, especially those with low CD4 counts. The optimal time to initiate ART in patients with tuberculosis is an important research question, and randomised controlled trials are addressing this issue.

Adolescent and young pregnant women at increased risk of mother-to-child transmission of HIV and poorer maternal and infant health outcomes: A cohort study at public facilities in the Nelson Mandela Bay Metropolitan district, Eastern Cape, South Africa

BACKGROUND South Africa (SA) has the highest burden of childhood HIV infection globally, and has high rates of adolescent and youth pregnancy. OBJECTIVE To explore risks associated with pregnancy in young HIV-infected women, we compared mother-to-child transmission (MTCT) of HIV and maternal and infant health outcomes according to maternal age categories. METHODS A cohort of HIV-positive pregnant women and their infants were followed up at three sentinel surveillance facilities in the Nelson Mandela Bay Metropolitan (NMBM) district, Eastern Cape Province, SA. Young women were defined as 24 years old and adolescents as 19 years. The effect of younger maternal age categories on MTCT and maternal and child health outcomes was assessed using log-binomial and Cox regression controlling for confounding, using women aged > 24 years as the comparison group. RESULTS Of 956 mothers, 312 (32.6%) were young women; of these, 65 (20.8%) were adolescents. The proportion of young pregnant women increased by 24% between 2009/10 and 2011/12 (from 28.3% to 35.1%). Young women had an increased risk of being unaware of their HIV status when booking (adjusted risk ratio (aRR) 1.37; 95% confidence interval (CI) 1.21 - 1.54), a reduced rate of antenatal antiretroviral therapy (ART) uptake (adjusted hazard ratio 0.46; 95% CI 0.31 - 0.67), reduced early infant HIV diagnosis (aRR 0.94; 95% CI 0.94 - 0.94), and increased MTCT (aRR 3.07; 95% CI 1.18 - 7.96; adjusted for ART use). Of all vertical transmissions, 56% occurred among young women. Additionally, adolescents had increased risks of first presentation during labour (aRR 3.78; 95% CI 1.06 - 13.4); maternal mortality (aRR 35.1; 95% CI 2.89 - 426) and stillbirth (aRR 3.33; 95% CI 1.53 - 7.25). CONCLUSION An increasing proportion of pregnant HIV-positive women in NMBM were young, and they had increased MTCT and poorer maternal and infant outcomes than older women. Interventions targeting young women are increasingly needed to reduce pregnancy, HIV infection and MTCT and improve maternal and infant outcomes if SA is to attain its Millennium Development Goals.

The effect of patient load on antiretroviral treatment programmatic outcomes at primary health care facilities in South Africa: a multicohort study.

INTRODUCTION South Africa has the largest antiretroviral therapy (ART) program worldwide with 970,000 people receiving ART in 2009. As patient numbers have expanded, rising levels of loss to followup (LTFU) have significantly reduced the effectiveness of the national ART program, and increasing virological failure has become apparent. A causal association between increased facility patient caseload and worsening ART outcomes in South Africa is, however, not established. A recent study from Mozambique indicated increased attrition from clinics with high pharmacy staff burden. However, there is little other sub-Saharan data comparing ART outcomes between facilities with varying patient caseloads. This knowledge is valuable, as the most efficient approaches to further upscale treatment access while maintaining good ART outcomes are critical to the success of ART programs. To determine the effect of increasing facility patient burden on ART program effectiveness, this study compared program outcomes among 54 government primary health care ART facilities in 4 South African provinces.

Antiretroviral treatment outcomes amongst older adults in a large multicentre cohort in South Africa.

Introduction Increasing numbers of patients are starting antiretroviral treatment (ART) at advanced age or reaching advanced age while on ART. We compared baseline characteristics and ART outcomes of older adults (aged ≥55 years) vs. younger adults (aged 25–54 years) in routine care settings in South Africa. Methods A multicentre cohort study of ART-naïve adults starting ART at 89 public sector facilities was conducted. Mortality, loss to follow-up (LTFU), immunological and virological outcomes until five years of ART were compared using competing-risks regression, generalised estimating equations and mixed-effects models. Results 4065 older adults and 86,006 younger adults were included. There were more men amongst older adults; 44.7% vs. 33.4%; RR = 1.34 (95% CI: 1.29–1.39). Mortality after starting ART was substantially higher amongst older adults, adjusted sub-hazard ratio (asHR) = 1.44 over 5 years (95% CI: 1.26–1.64), particularly for the period 7–60 months of treatment, asHR = 1.73 (95% CI: 1.44–2.10). LTFU was lower in older adults, asHR = 0.87 (95% CI: 0.78–0.97). Achievement of virological suppression was greater in older adults, adjusted odds ratio = 1.42 (95% CI: 1.23–1.64). The probabilities of viral rebound and confirmed virological failure were both lower in older adults, adjusted hazard ratios = 0.69 (95% CI: 0.56–0.85) and 0.64 (95% CI: 0.47–0.89), respectively. The rate of CD4 cell recovery (amongst patients with continuous viral suppression) was 25 cells/6 months of ART (95% CI: 17.3–33.2) lower in older adults. Conclusions Although older adults had better virological outcomes and reduced LTFU, their higher mortality and slower immunological recovery warrant consideration of age-specific ART initiation criteria and management strategies.

Antiretroviral Adherence Interventions in Southern Africa: Implications for Using HIV Treatments for Prevention

There is concern that the expansion of ART (antiretroviral treatment) programmes to incorporate the use of treatment as prevention (TasP) may be associated with low levels of adherence and retention in care, resulting in the increased spread of drug-resistant HIV. We review research published over the past year that reports on interventions to improve adherence and retention in care in Southern Africa, and discuss these in terms of their potential to support the expansion of ART programmes for TasP. We found eight articles published since January 2012, seven of which were from South Africa. The papers describe innovative models for ART care and adherence support, some of which have the potential to facilitate the ongoing scale- up of treatment programmes for increased coverage and TasP. The extent to which interventions from South Africa can be effectively implemented in other, lower-resource Southern African countries is unclear.

Comparing the effectiveness of efavirenz and nevirapine for first-line antiretroviral therapy in a South African multicentre cohort.

INTRODUCTION Current WHO guidelines for developing countries recommend efavirenz (EFV) and nevirapine (NVP) for first-line antiretroviral treatment (ART). This paper compares the effectiveness of EFV and NVP among ART-naive patients initiating treatment at 56 public health facilities in South Africa between January 2004 and December 2007. METHODS Participants were assigned to the EFV or NVP cohorts depending on their baseline ART regimen. Mortality, viral load suppression after 6 months and ART regimen change were compared between the cohorts using Cox proportional hazards models and logistic regression. RESULTS At initiation, 19 441 (71.1%) patients started EFV and 7909 (28.9%) started NVP treatment. The median follow-up period was 9.5 months (IQR 4.6-17.7). After adjustment, mortality was similar in the two cohorts, (adjusted HR = 1.07, 95% CI 0.89-1.28). Viral load suppression at 6 months was higher in the EFV cohort overall (adjusted odds ratio [AOR] = 1.29, 95% CI 1.05-1.59) and in women aged 16-40 years (AOR = 1.35, 95% CI 1.11-1.63) and women with CD4 counts <25 cells/µL (AOR = 1.95, 95% CI 1.01-3.76). Patients starting on EFV were 47% less likely to change regimen (AOR = 0.53, 95% CI 0.48-0.59). DISCUSSION These findings suggest the superior effectiveness of EFV for first-line ART compared with NVP and should be considered during development of future ART guidelines for high-burden regions.