Adherence to antiretroviral therapy and factors associated with non-adherence: a cohort study at two referral services in Brazil.

This cohort study evaluated non-adherence to antiretrovirals at referral services in Pernambuco, Brazil, 2016/2017, through self-report. A generalized mixed-effects model for binary outcomewas used. We assessed 542 participants with an adherence rate of 85.50%. A greater chance of non-adherence was associated with:a low/moderate level of nicotine dependence (OR = 2.79, p = 0.00, IC = 1.44-5.41); ≥7 tablets/day (OR = 6.14, p = 0.00, IC = 3.42-11.02); LPV/r (OR = 1.49, p = 0.6, IC = 0.98-2.26), ddI (OR = 3.34, p = 0.03, IC = 1.12-9.97), ABC (OR = 4.02, p = 0.05, IC = 1.01-16.03), RAL (OR = 2.49, p = 0.01, IC = 1.32-4.70) and DTG (OR = 4.65, p = 0.01, IC = 1.42-15.16); 6-10 year seropositive diagnosis (OR = 2.17, p = 0.01, IC = 1.20-3.92) and symptoms of depression (OR = 1.55, p = 0.03, IC = 1.03-2.33). Protective factors for non-adherence weres: ≥50 years (OR = 0.67, p = 0.06, IC = 0.45-1.01), secondary/higher education (OR = 0.48, p = 0.00, IC = 0.34-0.70), embarrassment at health service (OR = 0.49, p = 0.04, IC = 0.24-0.97), good understanding of antiretrovirals (OR = 0.62, p = 0.03, IC = 0.40-0.96), adverse event (OR = 0.74, p = 0,06, IC = 0.54-1.01), use of TDF (OR = 0.62, p = 0.01, IC = 0.43-0.90), NVP (OR = 0.41, p = 0.05, IC = 0.71-1.00) and EFZ (OR = 0.48, p = 0.01, IC = 0.29-0.80) and good knowledge of HIV/AIDS/ART. (OR = 0.67, p = 0.07, IC = 0.43-1.04). Variables with stronger association were those linked to ART. Systematic use of self-report adherence is recommended for priority groups.

Metabolic syndrome in patients on first-line antiretroviral therapy containing zidovudine or tenofovir in rural Lesotho, Southern Africa.

OBJECTIVE: To assess the prevalence of metabolic syndrome (MetS) among patients in rural Lesotho who are taking first-line antiretroviral therapy (ART) containing either zidovudine or tenofovir disoproxil. METHODS: Cross-sectional survey in 10 facilities in Lesotho among adult (≥16 years) patients on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART for ≥6 months. MetS was defined according to the International Diabetes Federation criteria. RESULTS: Among 1166 patients (65.8% female), 22.2% (95% CI: 19.3-25.3) of women and 6.3% (4.1-9.1) of men met the IDF definition of MetS (P < 0.001). In both sexes, there was no significant difference in MetS prevalence between NNRTIs. However, in women taking zidovudine as nucleoside reverse transcriptase inhibitor (NRTI), MetS prevalence was 27.9%, vs. 18.8% in those taking tenofovir. In the multivariate logistic regression allowing for socio-demographic and clinical covariates, ART containing zidovudine was associated with MetS in women (aOR 2.17 (1.46-3.22), P < 0.001) but not in men. CONCLUSION: In this study, taking ART containing zidovudine instead of tenofovir disoproxil was an independent predictor of MetS in women but not in men. This finding endorses WHO's recommendation of tenofovir as preferred NRTI.

Optimal antiretroviral therapy adherence as evaluated by CASE index score tool is associated with virological suppression in HIV-infected adults in Dakar, Senegal.

OBJECTIVE: To determine the prevalence and factors associated with optimal antiretroviral therapy (ART) adherence and virological failure (VLF) among HIV-infected adults enrolled in the national ART programme at the teaching hospital of Fann, Dakar, Senegal. METHODS: Cross-sectional study from 1 September 2013 to 30 January 2014. OUTCOMES: (1) optimal ART adherence by the Center for Adherence Support Evaluation (CASE) Index Score (>10) and (2) VLF (HIV RNA > 1000 copies/ml). Diagnostic accuracy of CASE Index Score assessed using sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and corresponding 95% confidence intervals (CIs). Multivariate logistic regression analysis was performed to identify independent factors associated with optimal adherence and VLF. RESULTS: Of 98 HIV-infected patients on ART, 68% were female. The median (IQR) age was 42 (20-50) years. A total of 57 of 98 (60%) were on ART more than 3 years, and majority (88%) were on NNRTI-based first-line ART regimen. A total of 79 of 98 (80%) patients reported optimal ART adherence, and only five of 84 (5.9%) had documented VLF. Patients with VLF were significantly more likely to have suboptimal ART adherence (17.7% vs. 2.9%; P = 0.02). CASE Index Score showed the best trade-off in Se (78.9%, 95% CI: 54.4-93.9%), Sp (20.0%, 95% CI: 11.1-31.7), PPV (22.4, 95% CI: 13.1-34.2%) and NPV (76.5%, 95% CI: 50.1-93.2), when used VLF threshold of HIV RNA >50 copies/ml. Factors independently associated with VLF were CASE Index Score <10 ([aOR] = 13.0, 95% CI: 1.1-147.9; P = 0.04) and being a boosted PI-based ART regimen ([aOR] = 27.0, 95% CI: 2.4-309.4; P = 0.008). CONCLUSIONS: Optimal ART adherence is achievable in a high proportion of HIV-infected adults in this study population. CASE Index Score was independently associated with virological outcomes, supporting usefulness of this low-cost ART adherence monitoring tool in this setting.

Nutritional status is the major factor affecting grip strength of African HIV patients before and during antiretroviral treatment.

OBJECTIVES: Low grip strength is a marker of frailty and a risk factor for mortality among HIV patients and other populations. We investigated factors associated with grip strength in malnourished HIV patients at referral to ART, and at 12 weeks and 2-3 years after starting ART. METHODS: The study involved HIV-infected Zambian and Tanzanian participants recruited to the NUSTART trial when malnourished (body mass index <18.5 kg/m2 ) and requiring ART. The relationship of grip strength to nutritional, infectious and demographic factors was assessed by multivariable linear regression at referral for ART (n = 1742) and after 12 weeks (n = 778) and 2-3 years of ART (n = 273). RESULTS: In analyses controlled only for sex, age and height, most nutrition and infection-related variables were associated with grip strength. However, in multivariable analyses, consistent associations were seen for fat-free mass index, mid-upper arm circumference, haemoglobin and systolic blood pressure, and a variable association with fat mass index in men. C-reactive protein and CD4 count had limited independent effects on grip strength, while receiving tuberculosis treatment was associated with weaker grip strength. CONCLUSIONS: In this population of originally malnourished HIV patients, poor grip strength was more strongly and independently associated with nutritional than with infection and inflammation variables. Programmes to improve health and survival of HIV patients should incorporate nutritional assessment and management and could use grip strength as a functional indicator of improving nutrition.

Behavioural disinhibition in the general population during the antiretroviral therapy roll-out in Sub-Saharan Africa: systematic review and meta-analysis.

OBJECTIVES: Improved life expectancy and reduced transmission probabilities due to ART may result in behavioural disinhibition - that is an increase in sexual risk behaviour in response to a perceived lower risk of HIV. We examined trends in sexual risk behaviour in the general population of sub-Saharan African countries 1999-2015. METHODS: We systematically reviewed scientific literature of sexual behaviour and reviewed trends in Demographic and Health Surveys. A meta-analysis on four indicators of sexual risk behaviour was performed: unprotected sex, multiple sexual partners, commercial sex and prevalence of sexually transmitted infections. RESULTS: Only two peer-reviewed studies met our inclusion criteria, while our review of DHS data spanned 18 countries and 16 years (1999-2015). We found conflicting trends in sexual risk behaviour. Reported unprotected sex decreased consistently across the 18 countries, for both sexes. In contrast, reporting multiple partners was decreasing over the period 1999 to the mid-2000s, yet has been consistently increasing thereafter. Similar trends were found for reported sexually transmitted infections and commercial sex (men only). CONCLUSIONS: In conclusion, we found no clear evidence of behavioural disinhibition due to expanded access to ART in sub-Saharan Africa. Substantial increases in condom use coincided with increases in reported multiple partners, commercial sex and sexually transmitted infections, especially during the period of ART scale-up. Further research is needed into how these changes might affect HIV transmission.

Outcomes of HIV-positive patients lost to follow-up in African treatment programmes.

OBJECTIVE: The retention of patients on antiretroviral therapy (ART) is key to achieving global targets in response to the HIV epidemic. Loss to follow-up (LTFU) can be substantial, with unknown outcomes for patients lost to ART programmes. We examined changes in outcomes of patients LTFU over calendar time, assessed associations with other study and programme characteristics and investigated the relative success of different tracing methods. METHODS: We performed a systematic review and logistic random-effects meta-regression analysis of studies that traced adults or children who started ART and were LTFU in sub-Saharan African treatment programmes. The primary outcome was mortality, and secondary outcomes were undocumented transfer to another programme, treatment interruption and the success of tracing attempts. RESULTS: We included 32 eligible studies from 12 countries in sub-Saharan Africa: 20 365 patients LTFU were traced, and 15 708 patients (77.1%) were found. Compared to telephone calls, tracing that included home visits increased the probability of success: the adjusted odds ratio (aOR) was 9.35 (95% confidence interval [CI] 1.85-47.31). The risk of death declined over calendar time (aOR per 1-year increase 0.86, 95% CI 0.78-0.95), whereas undocumented transfers (aOR 1.13, 95% CI 0.96-1.34) and treatment interruptions (aOR 1.31, 95% CI 1.18-1.45) tended to increase. Mortality was lower in urban than in rural areas (aOR 0.59, 95% CI 0.36-0.98), but there was no difference in mortality between adults and children. The CD4 cell count at the start of ART increased over time. CONCLUSIONS: Mortality among HIV-positive patients who started ART in sub-Saharan Africa, were lost to programmes and were successfully traced has declined substantially during the scale-up of ART, probably driven by less severe immunodeficiency at the start of therapy.

Growth in HIV-infected children on long-term antiretroviral therapy.

OBJECTIVES: To describe growth in HIV-infected children on long-term antiretroviral therapy (ART) and to assess social, clinical, immunological and virological factors associated with suboptimal growth. METHODS: This observational cohort study included all HIV-infected children at an urban ART site in South Africa who were younger than 5 years at ART initiation and with more than 5 years of follow-up. Growth was assessed using weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ) and body mass index (BMI)-for-age Z-scores (BAZ). Children were stratified according to pre-treatment anthropometry and age. Univariate and mixed linear analysis were used to determine associations between independent variables and weight and height outcomes. RESULTS: The majority of the 159 children presented with advanced clinical disease (90%) and immunosuppression (89%). Before treatment underweight, stunting and wasting were common (WAZ<-2 = 50%, HAZ<-2 = 73%, BAZ<-2 = 19%). Weight and BMI improved during the initial 12 months, while height improved over the entire 5-year period. Height at study exit was significantly worse for children with growth impairment at ART initiation (P < 0.001), and infants (<1 year) demonstrated superior improvement in terms of BMI (P = 0.04). Tuberculosis was an independent risk factor for suboptimal weight (P = 0.01) and height (P = 0.02) improvement. Weight gain was also hindered by lack of electricity (P = 0.04). Immune reconstitution and virological suppression were not associated with being underweight or stunted at study endpoint. CONCLUSIONS: Malnutrition was a major clinical concern for this cohort of HIV-infected children. Early ART initiation, tuberculosis co-infection management and nutritional interventions are crucial to ensure optimal growth in HIV-infected children.

Antiretroviral therapy status among people who died of AIDS-related causes from 2009 to 2013 in Brazil: a population-based study.

OBJECTIVE: To describe the antiretroviral therapy status of people living with HIV (PLHIV) who died of AIDS-related causes between 2009 and 2013. METHODS: We conducted a cross-sectional, population-based study. Data were obtained by linking the mortality information system and the national ART dispensing database. Trends were modelled using linear regression analysis. RESULTS: A total of 61 425 AIDS-related deaths were registered in Brazil between 2009 and 2013. Median age at death was 41 years (IQR: 33-49), and 65.7% (40 337) of deaths were among men; 47.2% (29 004) of PLHIV who died during the study period had never started treatment, 7.0% (4274) had discontinued it, 15.9% (9775) were on ART for 6 months or less and 29.9% (18 372) were on ART for more than 6 months. Only 1.3% of PLHIV were on third-line ARV regimens when they died. CONCLUSIONS: AIDS-related mortality remains a challenge even in a context of sustained universal access to antiretroviral treatment due to failure of service provision, not to therapy failure. Robust health policies closing gaps in the HIV continuum of care are crucial to further reduce mortality.

The rise and fall of tuberculosis in Malawi: associations with HIV infection and antiretroviral therapy.

OBJECTIVES: Since 1985, Malawi has experienced a dual epidemic of HIV and tuberculosis (TB) which has been moderated recently by the advent of antiretroviral therapy (ART). The aim of this study was to describe the association over several decades between HIV/AIDS, the scale-up of ART and TB case notifications. METHODS: Aggregate data were extracted from annual reports of the National TB Control Programme, the Ministry of Health HIV Department and the National Statistics Office. ART coverage was calculated using the total HIV population as denominator (derived from UNAIDS Spectrum software). RESULTS: In 1970, there were no HIV-infected persons but numbers had increased to a maximum of 1.18 million by 2014. HIV prevalence reached a maximum of 10.8% in 2000, thereafter decreasing to 7.5% by 2014. Numbers alive on ART increased from 2586 in 2003 to 536 527 (coverage 45.3%) by 2014. In 1985, there were 5286 TB cases which reached a maximum of 28 234 in 2003 and then decreased to 17 723 by 2014 (37% decline from 2003). There were increases in all types of new TB between 1998-2003 which then declined by 30% for extrapulmonary TB, by 37% for new smear-positive PTB and by 50% for smear-negative PTB. Previously treated TB cases reached a maximum of 3443 in 2003 and then declined by 42% by 2014. CONCLUSION: The rise and fall of TB in Malawi between 1985 and 2014 was strongly associated with HIV infection and ART scale-up; this has implications for ending the TB epidemic in high HIV-TB burden countries.

Evaluating facility-based antiretroviral therapy programme effectiveness: a pilot study comparing viral load suppression and retention rates.

OBJECTIVES: Increased demand for antiretroviral therapy (ART) services combined with plateaued levels of development assistance for HIV/AIDS requires that national ART programmes monitor programme effectiveness. In this pilot study, we compared commonly utilised performance metrics of 12- and 24-month retention with rates of viral load (VL) suppression at 15 health facilities in Uganda. METHODS: Retrospective chart review from which 12- and 24-month retention rates were estimated, and parallel HIV RNA VL testing on consecutive adult patients who presented to clinics and had been on ART for a minimum of six months. Rates of VL suppression were then calculated at each facility and compared to retention rates to assess the correlation between performance metrics. Multilevel logistic regression models predicting VL suppression and 12- and 24-month retention were constructed to estimate facility effects. RESULTS: We collected VL samples from 2961 patients and found that 88% had a VL ≤1000 copies/ml. Facility rates of VL suppression varied between 77% and 96%. When controlling for patient mix, a significant variation in facility performance persisted. Retention rates at 12 and 24 months were 91% and 79%, respectively, with a comparable facility-level variation. However, neither 12-month (ρ = 0.16) nor 24-month (ρ = -0.19) retention rates were correlated with facility rates of VL suppression. CONCLUSIONS: Retaining patients in care and suppressing VL are both critical outcomes. Given the lack of correlation noted in this study, the utilisation of VL monitoring may be necessary to truly assess the effectiveness of health facilities delivering ART services.

Stable patients and patients with advanced disease: consensus definitions to support sustained scale up of antiretroviral therapy.

OBJECTIVE: As guidelines are evolving towards recommending starting antiretroviral therapy (ART) in all HIV-positive individuals irrespective of clinical and immunological status, HIV programmes will be challenged to manage an increasingly diverse set of patient needs. To support global guideline recommendations for differentiated service delivery, WHO developed consensus definitions for two distinct patient populations: patients presenting with advanced disease and patients who are stable on ART. METHODS: An expert panel consisting of 73 respondents from 28 countries across all six WHO regions supported the development of these definitions. The panel included clinicians, researchers, programme managers, technical advisors and patient group representatives. RESULTS: Patients presenting with advanced disease at presentation to care were defined as CD4 count <200 CD4 cells/mm(3) or WHO Stage III & IV defining illness. Patients stable on ART were defined as those who were receiving ART for at least 1 year with no adverse drug reactions requiring regular monitoring, no current illnesses or pregnancy, a good understanding of lifelong adherence, and evidence of treatment success. Treatment success was defined as two consecutive undetectable viral load measures or, in the absence of viral load monitoring, rising CD4 counts or CD4 counts above 200 cells/mm(3) and an objective adherence measure. CONCLUSIONS: Patients who are stable on ART should be offered a less intensive care package that can lead to improved outcomes while saving resources, including less frequent clinic visits, out-of-clinic drug refills and reduced laboratory monitoring. This will allow for clinic resources to be directed towards reducing morbidity and mortality among patients presenting with advanced disease.

Follow-up and programmatic outcomes of HIV-exposed infants registered in a large HIV centre in Lilongwe, Malawi: 2012-2014.

OBJECTIVE: To assess follow-up and programmatic outcomes of HIV-exposed infants at Martin Preuss Centre, Lilongwe, from 2012 to 2014. METHODS: Retrospective cohort study using routinely collected HIV-exposed infant data. Data were analysed using frequencies and percentages in Stata v.13. RESULTS: Of 1035 HIV-exposed infants registered 2012-2014, 79% were available to be tested for HIV and 76% were HIV-tested either with DNA-PCR or rapid HIV test serology by 24 months of age. Sixty-five infants were found to be HIV-positive and 43% were started on antiretroviral therapy (ART) at different ages from 6 weeks to 24 months. Overall, 48% of HIV-exposed infants were declared lost-to-follow-up in the database. Of these, 69% were listed for tracing; of these, 78% were confirmed as lost-to-follow-up through patient charts; of these, 51% were traced; and of these, 62% were truly not in care, the remainder being wrongly classified. Commonest reasons for being truly not in care were mother/guardian unavailability to bring infants to Martin Preuss Centre, forgetting clinic appointments and transport expenses. Of these 86 patients, 36% were successfully brought back to care and 64% remained lost-to-follow-up. CONCLUSION: Loss to follow-up remains a huge challenge in the care of HIV-exposed infants. Active tracing facilitates the return of some of these infants to care. However, programmatic data documentation must be urgently improved to better follow-up and link HIV-positive children to ART.

Adherence clubs for long-term provision of antiretroviral therapy: cost-effectiveness and access analysis from Khayelitsha, South Africa.

OBJECTIVES: As the scale of the South African HIV epidemic calls for innovative models of care that improve accessibility for patients while overcoming chronic human resource shortages, we (i) assess the cost-effectiveness of lay health worker-led group adherence clubs, in comparison with a nurse-driven 'standard of care' and (ii) describe and evaluate the associated patient cost and accessibility differences. METHODS: Our cost-effectiveness analysis compares an 'adherence club' innovation to conventional nurse-driven care within a busy primary healthcare setting in Khayelitsha, South Africa. In each alternative, we calculate provider costs and estimate rates of retention in care and viral suppression as key measures of programme effectiveness. All results are presented on an annual or per patient-year basis. In the same setting, a smaller sample of patients was interviewed to understand the direct and indirect non-healthcare cost and access implications of the alternatives. Access was measured using McIntyre and colleagues' 2009 framework. RESULTS: Adherence clubs were the more cost-effective model of care, with a cost per patient-year of $300 vs. $374 and retention in care at 1 year of 98.03% (95% CI 97.67-98.33) for clubs vs. 95.49% (95% CI 95.01-95.94) for standard of care. Viral suppression in clubs was 99.06% (95% CI 98.82-99.27) for clubs vs. 97.20% (95% CI 96.81-97.56) for standard of care. When interviewed, club patients reported fewer missed visits, shorter waiting times and higher acceptability of services compared to standard of care. CONCLUSIONS: Adherence clubs offer the potential to enhance healthcare efficiency and patient accessibility. Their scale-up should be supported.

CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone.

OBJECTIVE: CD4 count decline often triggers antiretroviral regimen switches in resource-limited settings, even when viral load testing is available. We therefore compared CD4 failure and CD4 trends in patients with viraemia with or without antiretroviral resistance. METHODS: Retrospective cohort study investigating the association of HIV drug resistance with CD4 failure or CD4 trends in patients on first-line antiretroviral regimens during viraemia. Patients with viraemia (HIV RNA >1000 copies/ml) from two HIV treatment programmes in South Africa (n = 350) were included. We investigated the association of M184V and NNRTI resistance with WHO immunological failure criteria and CD4 count trends, using chi-square tests and linear mixed models. RESULTS: Fewer patients with the M184V mutation reached immunologic failure criteria than those without: 51 of 151(34%) vs. 90 of 199 (45%) (P = 0.03). Similarly, 79 of 220 (36%) patients, who had major NNRTI resistance, had immunological failure, whereas 62 of 130 (48%) without (chi-square P = 0.03) did. The CD4 count decline among patients with the M184V mutation was 2.5 cells/mm(3) /year, whereas in those without M184V it was 14 cells/mm(3) /year (P = 0.1), but the difference in CD4 count decline with and without NNRTI resistance was marginal. CONCLUSION: Our data suggest that CD4 count monitoring may lead to inappropriate delayed therapy switches for patients with HIV drug resistance. Conversely, patients with viraemia but no drug resistance are more likely to have a CD4 count decline and thus may be more likely to be switched to a second-line regimen.

Cost/efficacy analysis of preferred Spanish AIDS study group regimens and the dual therapy with lopinavir/ritonavir plus lamivudine for initial ART in HIV infected adults.

INTRODUCTION: The National AIDS Plan and the Spanish AIDS study group (GESIDA) proposes "preferred regimens" (PR) of antiretroviral treatment (ART) as initial therapy in HIV-infected patients. In 2013, the recommended regimens were all triple therapy regimens. The Gardel Study assessed the efficacy of a dual therapy (DT) combination of lopinavir/ritonavir (LPV/r) plus lamivudine (3TC). Our objective is to evaluate the GESIDA PR and the DT regimen LPV/r+3TC cost/efficacy ratios. METHODS: Decision tree models were built. EFFICACY: probability of having viral load <50 copies/mL at week 48. ART regime cost: costs of ART, adverse effects, and drug resistance tests during the first 48 weeks. RESULTS: Cost/efficacy ratios varied between 5,817 and 13,930 euros per responder at 48 weeks, for the DT of LPV/r+3TC and tenofovir DF/emtricitabine+raltegravir, respectively. CONCLUSIONS: Taking into account the official Spanish prices of ART, the most efficient regimen was DT of LPV/r+3TC, followed by the triple therapy with non-nucleoside containing regimens.

Prediction of higher cost of antiretroviral therapy (ART) according to clinical complexity. A validated clinical index.

BACKGROUND: The financing of antiretroviral therapy (ART) is generally determined by the cost incurred in the previous year, the number of patients on treatment, and the evidence-based recommendations, but not the clinical characteristics of the population. OBJECTIVE: To establish a score relating the cost of ART and patient clinical complexity in order to understand the costing differences between hospitals in the region that could be explained by the clinical complexity of their population. METHODS: Retrospective analysis of patients receiving ART in a tertiary hospital between 2009 and 2011. Factors potentially associated with a higher cost of ART were assessed by bivariate and multivariate analysis. Two predictive models of "high-cost" were developed. The normalized estimated (adjusted for the complexity scores) costs were calculated and compared with the normalized real costs. RESULTS: In the Hospital Index, 631 (16.8%) of the 3758 patients receiving ART were responsible for a "high-cost" subgroup, defined as the highest 25% of spending on ART. Baseline variables that were significant predictors of high cost in the Clinic-B model in the multivariate analysis were: route of transmission of HIV, AIDS criteria, Spanish nationality, year of initiation of ART, CD4+ lymphocyte count nadir, and number of hospital admissions. The Clinic-B score ranged from 0 to 13, and the mean value (5.97) was lower than the overall mean value of the four hospitals (6.16). CONCLUSIONS: The clinical complexity of the HIV patient influences the cost of ART. The Clinic-B and Clinic-BF scores predicted patients with high cost of ART and could be used to compare and allocate costs corrected for the patient clinical complexity.

Effect of cotrimoxazole prophylaxis on malaria occurrence in HIV-infected patients on antiretroviral therapy in sub-Saharan Africa.

OBJECTIVE: To systematically review the evidence on the effect of cotrimoxazole (CTX) on malaria in HIV-positive individuals on antiretroviral therapy (ART). METHODS: Web of Science, PubMed and MEDLINE, EMBASE, Global Health and Cochrane Library databases were searched using terms for malaria, HIV and CTX. Studies meeting the inclusion criteria were reviewed and assessed for bias and confounding. RESULTS: Six studies (in Uganda, Kenya, Malawi, Zambia and Zimbabwe) had relevant data on the effect of CTX on malaria in patients on ART: four were observational cohort studies (OCS) and two were randomised controlled trials (RCTs); two were in children and one in women only. Samples sizes ranged from 265 to 2200 patients. Four studies compared patients on ART and CTX with patients on ART alone; 2 (RCTs) found a significant increase in smear-positive malaria on ART alone: (IRR 32.5 CI = 8.6-275.0 and HR 2.2 CI = 1.5-3.3) and 2 (OCS) reported fewer parasitaemia episodes on CTX and ART (OR 0.85 CI = 0.65-1.11 and 3.6% vs. 2.4% of samples P = 0.14). One OCS found a 76% (95% CI = 63-84%) vs. 83% (95% CI = 74-89%) reduction in malaria incidence in children on CTX and ART vs. on CTX only, when both were compared with HIV-negative children. The other reported a 64% reduction in malaria incidence after adding ART to CTX (RR = 0.36, 95% CI = 0.18-0.74). The 2 RCTs were unblinded. Only one study reported adherence to CTX and ART, and only two controlled for baseline CD4 count. CONCLUSION: Few studies have investigated the effect of CTX on malaria in patients on ART. Their findings suggest that CTX is protective against malaria even among patients on ART.

Improvement in mortality and retention among adult HIV-infected patients in the first 12 months of antiretroviral therapy in Dodoma urban district, Tanzania.

OBJECTIVE: To determine mortality and retention in ART programmes in Tanzania, between 2010 and 2013. METHODS: Retrospective routinely collected data were analysed from people starting ART in the period 2010-2013. Mortality and retention over the first 12 months on ART were compared across the 4 years, and adjustment was made for individual level potential confounders. RESULTS: Data from 3844 people (70.6% female) starting ART were analysed. Mortality in the first year declined from 11.4% in 2010 to 4.9% in 2013, and retention after 12 months increased from 77.8% in 2010 to 98.1% in 2013. Mortality was inversely associated with CD4 count, lowest among those with CD4 350+ cells/µl [adjusted odds ratio (AOR) = 0.03, 95% CI 0.01-0.03], associated with male sex (AOR = 1.79, 95% CI 1.39-2.31), but not age. Lost to follow-up (LTFU) was lowest among those with CD4 = 350+ cells/µl AOR = 0.20, 95% CI 0.10-0.30), but not associated with age or sex, and higher in urban health facilities (AOR = 1.88, 95% CI 1.15-3.09). After adjustment for individual level characteristics, there was a statistically significant yearly improvement in mortality (AOR = 0.31, 95% CI (0.21-0.44) and LTFU (AOR = 0.06, 95% CI 0.04-0.10). CONCLUSION: Mortality and retention in the first 12 months on ART have significantly improved over the 4 years from 2010 to 2013. These improvements may indicate better services, earlier initiation on ART, and strengthened systems to provide ART in Tanzania. These results refute the worries that earlier initiation on ART might lead to lower retention in the ART programme.

'I was thinking too much': experiences of HIV-positive adults with common mental disorders and poor adherence to antiretroviral therapy in Zimbabwe.

OBJECTIVE: To document the lived experiences of people with both poor mental health and suboptimal adherence to antiretroviral therapy in high HIV prevalence settings. METHODS: In-depth qualitative interviews were conducted with 47 (female = 31) HIV-positive adults who scored above the cut-point on a locally validated scale for common mental disorders (CMDs). Purposive sampling was used to recruit participants with evidence of poor adherence. Six additional key informant interviews (female = 6) were conducted with healthcare workers. Data were collected and analysed inductively by an interdisciplinary coding team. RESULTS: The major challenges faced by participants were stressors (poverty, stigma, marital problems) and symptoms of CMDs ('thinking too much', changes to appetite and sleep, 'burdened heart' and low energy levels). Thinking too much, which appears closely related to rumination, was the symptom with the greatest negative impact on adherence to antiretroviral therapy among HIV-positive adults with CMDs. In turn, thinking too much was commonly triggered by the stressors faced by people living with HIV/AIDS, especially poverty. Finally, participants desired private counselling, access to income-generating activities and family engagement in mental health care. CONCLUSIONS: Better understanding of the local expression of mental disorders and of underlying stressors can inform the development of culturally sensitive interventions to reduce CMDs and poor adherence to antiretroviral therapy.

Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial.

OBJECTIVE: T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery. METHODS: A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/µl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry. RESULTS: Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported. CONCLUSION: Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa.