Validating five questions of antiretroviral nonadherence in a public-sector treatment program in rural South Africa

Simple questions are the most commonly used measures of antiretroviral treatment (ART) adherence in sub-Saharan Africa (SSA), but rarely validated. We administered five adherence questions in a public-sector primary care clinic in rural South Africa: 7-day recall of missed doses, 7-day recall of late doses, a six-level Likert item, a 30-day visual analogue scale of the proportion of doses missed, and recall of the time when an ART dose was last missed. We estimated question sensitivity and specificity in detecting immunologic (or virologic) failure assessed within 45 days of the adherence question date. Of 165 individuals, 7% had immunologic failure; 137 individuals had viral loads with 9% failure detected. The Likert item performed best for immunologic failure with sensitivity/specificity of 100%/5% (when defining nonadherence as self-reported adherence less than "excellent"), 42%/55% (less than "very good"), and 25%/95% (less than "good"). The remaining questions had sensitivities ≤17%, even when the least strict cutoffs defined nonadherence. When we stratified the analysis by gender, age, or education, question performance was not substantially better in any of the subsamples in comparison to the total sample. Five commonly used adherence questions performed poorly in identifying patients with treatment failure in a public-sector ART program in SSA. Valid adherence measurement instruments are urgently required to identify patients needing treatment support and those most at risk of treatment failure. Available estimates of ART adherence in SSA are mostly based on studies using adherence questions. It is thus unlikely that our understanding of ART adherence in the region is correct.     

The spectrum of psoriatic arthritis in a South African cohort

The aim of this study was to describe the clinical features of patients with psoriatic arthritis (PsA) in a South African cohort. This is a retrospective analysis of patients contributing to development of the international classification criteria for PsA, ClASsification criteria for Psoriatic ARthritis (CASPAR). Patients were all seen at the arthritis clinics at Groote Schuur Hospital, Cape Town. Demographic, clinical, laboratory and radiographic information was collected. This study describes the relevant findings relating to the clinical profile of the patients seen at our centre as well as the effect of family history and/or dactylitis in determining the severity of psoriatic arthritis. There were 45 patients with a male to female ratio of 1:1.25. The mean age of psoriasis onset was 38.34 years (SD 15.54), whilst that of arthritis onset was 43.86 years (SD 13.4). Polyarthritis was the commonest pattern and sacro-iliitis was uncommon. Dactylitis was present in 26%. The presence of family history or of dactylitis did not predict more severe disease. There was a significant correlation between tender and swollen joints. The mean Health Assessment Questionnaire (HAQ) score was 1.05. Eighty-three percent showed evidence of radiological changes, and distal interphalangeal (DIP) erosions were found in 54%. Arthritis mutilans was present in 31%. There were no black subjects in the cohort. The clinical patterns of PsA in our cohort are similar to those reported elsewhere. The paucity of blacks amongst this cohort requires further study. PsA-specific measures of disease activity need to be developed. PsA causes significant joint damage and disability.     

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 children's 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.     

Effectiveness of naltrexone in a community treatment program

OBJECTIVE: In several large, well-designed, randomized, double-blind studies, the opiate antagonist naltrexone demonstrated efficacy in the treatment of alcohol dependence. Specifically, when combined with certain psychosocial therapies, naltrexone reduces the number of drinking days, heavy drinking, and time to relapse to alcohol use in alcohol-dependent individuals. Whether this efficacy can be generalized to individuals who have alcohol use disorders and present for treatment at front-line community treatment programs has not been well established. METHODS: A total of 145 patients who presented for treatment at a rural community substance abuse treatment center were randomized to receive naltrexone 50 mg daily plus usual program treatment (n = 54), placebo plus usual treatment (n = 43), or usual treatment alone (n = 48) for 12 week. A total of 133 participants had at least one follow-up visit. Primary outcome measures included percent days drinking, average drinks per drinking day, average drinks per day, heavy drinking days (four or more for women and six or more for men), and time to first heavy drinking day. Secondary measures included changes in serum biological markers (alkaline phosphatase, alanine transaminase, aspartate transaminase, and gamma-glutamyltransferase), craving, and psychosocial functioning. RESULTS: In the intention-to-treat analysis, there were no between-group differences for any of the primary drinking outcomes at 12 weeks. In post hoc exploratory analyses, the entire sample of participants was divided into two new groups: (1) people who drank during the 2 weeks before the start of medication (entry drinkers) and (2) people who did not drink during this interval (entry abstainers). Entry abstainers were at an advantage at study entry in that they were significantly more likely to have an inpatient hospitalization immediately before entry into outpatient treatment. Mixed-model analysis of variance revealed a main effect for entry group at the 12-week treatment endpoint on the primary outcome measures of percent days drinking, average drinks per drinking day, average drinks per day, heavy drinking days, and time to first heavy drinking day. Participants in any of the randomized groups who were entry abstainers had significantly better improvement on all of the primary outcome measures. The abstainer groups that were randomized to placebo and usual treatment had significantly better outcomes than the entry drinkers in those perspective groups. However, for the naltrexone-treated group, entry drinkers and entry abstainers had similar improvement in drinking-related outcomes. CONCLUSIONS: These data suggest that naltrexone may offer particular benefit to patients who continue to drink during the early stages of the trial as compared with those who have achieved abstinence before treatment entry.     

Nontuberculous mycobacteria: defining disease in a prospective cohort of South African miners.

A gold mining work force was followed prospectively over 1 yr for sputum nontuberculous mycobacterial (NTM) isolates. NTM were isolated from 118 men, of whom 32 (27%) met the American Thoracic Society (ATS) case-definitions for pulmonary NTM disease (23 M. kansasii, seven M. scrofulaceum, one M. avium, and one M. abscessus). Determining isolate significance was difficult because most men had been started on presumptive TB treatment before isolate identification (70%). Histologic criteria were considered inappropriate for this high M. tuberculosis incidence population, particularly for patients who had stabilized on presumptive TB treatment. Among men not meeting case-definitions, indicators of disease were significantly more prevalent for M. kansasii than for M. fortuitum, the local laboratory contaminant (ORs: 6.5 for cough, 7. 2 for smear-positivity, 36.0 for radiologic changes, and 14.3 for presumptive TB treatment), suggesting underdiagnosis of M. kansasii disease. Of 53 men with definite or possible M. kansasii disease, 18 (34%) were HIV-positive. HIV-associated M. kansasii disease occurred at an early stage of immunosuppression (median CD4 count, 381 x 10(6)/L) with a good outcome (83% cured after 12 mo of treatment). ATS case-definitions for NTM disease are difficult to apply in this population, and treatment decisions should be guided by the pathogenic potential of the isolate.     

Effectiveness of DOT for tuberculosis treatment outcomes: a prospective cohort study in Bangkok, Thailand.

SETTING: All health care centres under the Department of Health, Bangkok Metropolitan Administration. OBJECTIVES: To investigate patterns of drug administration for tuberculosis (TB) patients and to determine whether these patterns affect treatment success rates. DESIGN: In a prospective cohort study conducted during May 2004 to November 2005, newly diagnosed TB patients aged >/=15 years were enrolled after giving informed consent. The cohort was followed until treatment outcome. Structured questionnaires were used to interview patients three times: at the first visit, at the end of the intensive phase and at treatment completion. Data were also collected from treatment cards. RESULTS: Five patterns of drug administration were used in the health centres: centre-based directly observed treatment (DOT), family-based DOT, self-administered treatment (SAT), centre-based DOT + SAT and centre- + family-based DOT. The pattern of drug administration had a significant impact on treatment success (P < 0.001). Using unconditional binary multiple logistic regression controlling for confounding factors, centre- + family-based DOT had the highest success rates compared with centre-based DOT (OR 20.9, 95%CI 5.0-88.3). CONCLUSION: The pattern of drug administration impacted on treatment success. Centre- + family-based DOT, family-based DOT and centre-based DOT + SAT achieved higher rates of treatment success than the World Health Organization target. Centre-based DOT had the lowest success.     

Hepatotoxicity in an African antiretroviral therapy cohort: the effect of tuberculosis and hepatitis B

OBJECTIVE: Hepatotoxicity is a significant complication of antiretroviral therapy (ART). We assessed the incidence of and risk factors for hepatotoxicity among HIV-infected individuals on ART in South Africa. DESIGN: We conducted a retrospective cohort study in a workplace HIV care program in South Africa which uses a first-line regimen of efavirenz, zidovudine, and lamivudine and provides routine clinical and laboratory monitoring. METHODS: We included subjects with baseline and follow-up alanine transaminase and aspartate aminotransferase tests. Severe hepatotoxicity cases were identified during the first 12 months of ART. Potential risk factors, including concomitant medication use, tuberculosis, and hepatitis B and C, were determined from clinical records, database queries, and serological testing. Associations with hepatotoxicity were investigated using Cox proportional hazards modeling. RESULTS: Of the 868 subjects (94% male, median age 41 years), the median nadir CD4 cell count was 136/microl, 25% received concomitant tuberculosis treatment during ART, and 17% of a randomly selected subset were positive for hepatitis B surface antigen (HBsAg). We identified 7.7 episodes of severe hepatotoxicity per 100 person-years. Tuberculosis treatment increased risk 8.5 fold, positive HBsAg 3.0 fold, and nadir CD4 cells count < 100/microl 1.9 fold. Importantly, the fraction of patients with severe hepatotoxicity on ART (4.6%) was similar to the fraction with liver enzyme elevations > 5 times the upper limit of normal before starting ART (4%). CONCLUSIONS: In this African ART cohort, we found a low incidence of and minimal morbidity due to hepatotoxicity. HBsAg and concomitant tuberculosis therapy significantly increased the risk of hepatotoxicity.     

Risk factors for poor virological outcome at 12 months in a workplace-based antiretroviral therapy programme in South Africa: A cohort study

Background

To investigate dynamic fluctuations of serum viral load and peripheral T-lymphocyte subpopulations of chronic hepatitis B patients and their correlation during entecavir therapy.

Methods

Fifty-five patients received entecavir 0.5 mg/d therapy. Serum HBV DNA load was measured by Real-Time-PCR, and the levels of peripheral T-lymphocyte subpopulations by flow cytometry biweekly, every four weeks and every eight weeks during weeks 1–12, 13–24 and 24–48, respectively. Multilevel modelling was used to analyse the relationship between these variables.

Results

Of the 55 patients, all HBeAg positive and with detectable HBV DNA, the majority (81.8%) had serum levels of HBV DNA over 10⁷ copies per milliliter. HBV viral load dropped sharply during the first two weeks. In 28 and 43 patients, the level became undetectable from week 24 and 48, respectively. Using pre-therapy level as the reference, a significant decrease in CD8⁺ T cells and increase in CD4⁺ T cells were found from week 12. Both parameters and CD4⁺/CD8⁺ ratio steadily improved throughout the 48 weeks. Multilevel analyses showed that the level of decrement of HBV DNA was associated with the increment of T-lymphocyte activities only in the later period (4–48 week). After 4 weeks of therapy, for each log₁₀ scale decrement of HBV DNA, the percentage of CD4⁺ lymphocyte was increased by 0.49 and that of CD8⁺ decreased by 0.51.

Conclusion

T-lymphocyte subpopulations could be restored partially by entecavir treatment in patients with chronic hepatitis B concurrently with reduction of viremia.     

Intimate partner violence: associations with low infant birthweight in a South African birth cohort

Violence against women is a global public health problem. Exposure to intimate partner violence (IPV) during pregnancy has been associated with a number of adverse maternal and fetal outcomes, including delivery of a low birthweight (LBW) infant. However, there is a paucity of data from low-middle income countries (LMIC). We examined the association between antenatal IPV and subsequent LBW in a South African birth cohort. This study reports data from the Drakenstein Child Lung Health Study (DCLHS), a multidisciplinary birth cohort investigation of the influence of a number of antecedent risk factors on maternal and infant health outcomes over time. Pregnant women seeking antenatal care were recruited at two different primary care clinics in a low income, semi-rural area outside Cape Town, South Africa. Antenatal trauma exposure was assessed using the Childhood Trauma Questionnaire (CTQ) and an IPV assessment tool specifically designed for the purposes of this study. Potential confounding variables including maternal sociodemographics, pregnancy intention, partner support, biomedical and mental illness, substance use and psychosocial risk were also assessed. Bivariate and multiple regression analyses were performed to determine the association between IPV during pregnancy and delivery of an infant with LBW and/or low weight-for-age z (WAZ) scores. The final study sample comprised 263 mother-infant dyads. In multiple regression analyses, the model run was significant [r ² ?=?0.14 (adjusted r ² ?=?0.11, F(8, 212) = 4.16, p?=?0.0001]. Exposure to physical IPV occurring during the past year was found to be significantly associated with LBW [t?=??2.04, p?=?0.0429] when controlling for study site (clinic), maternal height, ethnicity, socioeconomic status, substance use and childhood trauma. A significant association with decreased WAZ scores was not demonstrated. Exposure of pregnant women to IPV may impact newborn health. Further research is needed in this field to assess the relevant underlying mechanisms, to inform public health policies and to develop appropriate trauma IPV interventions for LMIC settings.     

Growth response to antiretroviral treatment in HIV‐infected children: a cohort study from Lilongwe,Malawi

Objective Malnutrition is common in HIV‐infected children in Africa and an indication for antiretroviral treatment (ART). We examined anthropometric status and response to ART in children treated at a large public‐sector clinic in Malawi. Methods All children aged <15 years who started ART between January 2001 and December 2006 were included and followed until March 2008. Weight and height were measured at regular intervals from 1 year before to 2 years after the start of ART. Sex‐ and age‐standardized z‐scores were calculated for weight‐for‐age (WAZ) and height‐for‐age (HAZ). Predictors of growth were identified in multivariable mixed‐effect models. Results A total of 497 children started ART and were followed for 972 person‐years. Median age (interquartile range; IQR) was 8 years (4–11 years). Most children were underweight (52% of children), stunted (69%), in advanced clinical stages (94% in WHO stages 3 or 4) and had severe immunodeficiency (77%). After starting ART, median (IQR) WAZ and HAZ increased from ?2.1 (?2.7 to ?1.3) and ?2.6 (?3.6 to ?1.8) to ?1.4 (?2.1 to ?0.8) and ?1.8 (?2.4 to ?1.1) at 24 months, respectively (P < 0.001). In multivariable models, baseline WAZ and HAZ scores were the most important determinants of growth trajectories on ART. Conclusions Despite a sustained growth response to ART among children remaining on therapy, normal values were not reached. Interventions leading to earlier HIV diagnosis and initiation of treatment could improve growth response.