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.

Home-based versus mobile clinic HIV testing and counseling in rural Lesotho: a cluster-randomized trial.

BACKGROUND: The success of HIV programs relies on widely accessible HIV testing and counseling (HTC) services at health facilities as well as in the community. Home-based HTC (HB-HTC) is a popular community-based approach to reach persons who do not test at health facilities. Data comparing HB-HTC to other community-based HTC approaches are very limited. This trial compares HB-HTC to mobile clinic HTC (MC-HTC). METHODS AND FINDINGS: The trial was powered to test the hypothesis of higher HTC uptake in HB-HTC campaigns than in MC-HTC campaigns. Twelve clusters were randomly allocated to HB-HTC or MC-HTC. The six clusters in the HB-HTC group received 30 1-d multi-disease campaigns (five villages per cluster) that delivered services by going door-to-door, whereas the six clusters in MC-HTC group received campaigns involving community gatherings in the 30 villages with subsequent service provision in mobile clinics. Time allocation and human resources were standardized and equal in both groups. All individuals accessing the campaigns with unknown HIV status or whose last HIV test was >12 wk ago and was negative were eligible. All outcomes were assessed at the individual level. Statistical analysis used multivariable logistic regression. Odds ratios and p-values were adjusted for gender, age, and cluster effect. Out of 3,197 participants from the 12 clusters, 2,563 (80.2%) were eligible (HB-HTC: 1,171; MC-HTC: 1,392). The results for the primary outcomes were as follows. Overall HTC uptake was higher in the HB-HTC group than in the MC-HTC group (92.5% versus 86.7%; adjusted odds ratio [aOR]: 2.06; 95% CI: 1.18-3.60; p = 0. 011). Among adolescents and adults ≥ 12 y, HTC uptake did not differ significantly between the two groups; however, in children <12 y, HTC uptake was higher in the HB-HTC arm (87.5% versus 58.7%; aOR: 4.91; 95% CI: 2.41-10.0; p<0.001). Out of those who took up HTC, 114 (4.9%) tested HIV-positive, 39 (3.6%) in the HB-HTC arm and 75 (6.2%) in the MC-HTC arm (aOR: 0.64; 95% CI: 0.48-0.86; p = 0.002). Ten (25.6%) and 19 (25.3%) individuals in the HB-HTC and in the MC-HTC arms, respectively, linked to HIV care within 1 mo after testing positive. Findings for secondary outcomes were as follows: HB-HTC reached more first-time testers, particularly among adolescents and young adults, and had a higher proportion of men among participants. However, after adjusting for clustering, the difference in male participation was not significant anymore. Age distribution among participants and immunological and clinical stages among persons newly diagnosed HIV-positive did not differ significantly between the two groups. Major study limitations included the campaigns' restriction to weekdays and a relatively low HIV prevalence among participants, the latter indicating that both arms may have reached an underexposed population. CONCLUSIONS: This study demonstrates that both HB-HTC and MC-HTC can achieve high uptake of HTC. The choice between these two community-based strategies will depend on the objective of the activity: HB-HTC was better in reaching children, individuals who had never tested before, and men, while MC-HTC detected more new HIV infections. The low rate of linkage to care after a positive HIV test warrants future consideration of combining community-based HTC approaches with strategies to improve linkage to care for persons who test HIV-positive. TRIAL REGISTRATION: ClinicalTrials.gov NCT01459120. Please see later in the article for the Editors' Summary.

Adoption of new HIV treatment guidelines and drug substitutions within first-line as a measure of quality of care in rural Lesotho: health centers and hospitals compared.

OBJECTIVE: In 2007, Lesotho launched new national antiretroviral treatment (ART) guidelines, prioritising tenofovir and zidovudine over stavudine as a backbone together with lamivudine. We compared the rate of adoption of these new guidelines and substitution of first-line drugs by health centers (HC) and hospitals in two catchment areas in rural Lesotho. METHODS: Retrospective cohort analysis. Patients aged ≥16 years were stratified into a HC- and a hospital-group. MAIN OUTCOME VARIABLES: Type of backbone at ART-initiation (i), substitutions within first line (ii) and type of backbone among patients retained by December 2010 (iii). A multiple logistic regression model including HC vs. hospital, patient characteristics (sex, age, WHO-stage, baseline CD4-count, concurrent pregnancy, concurrent tuberculosis treatment) and year of ART-start, was used. RESULTS: Of 3936 adult patients initiated on ART between 2007 and 2010, 1971 started at hospitals and 1965 at HCs. Hospitals were more likely to follow the new guidelines as measured by prescription of backbones without stavudine (Odds-ratio 1.55; 95%CI: 1.32-1.81) and had a higher rate of drug substitutions while on first-line ART (2.39; 1.83-3.13). By December 2010, patients followed at health centres were more likely to still receive stavudine (2.28; 1.83-2.84). CONCLUSIONS: Health centers took longer to adopt the new guidelines and substituted drugs less frequently. Decentralised ART-programmes need close support, supervision and mentoring to absorb new guidelines and to adhere to them.

Still Far From 90-90-90: Virologic Outcomes of Children on Antiretroviral Therapy in Nurse-led Clinics in Rural Lesotho.

This survey assessed virologic outcomes of children on antiretroviral therapy and potential predictors in 10 nurse-led clinics in Lesotho. Viral suppression was achieved in 72% of the 191 children. No predictors for virologic outcome were found, underlining the need for routine viral load testing in resource-limited settings to achieve 90-90-90.

Higher rates of metabolic syndrome among women taking zidovudine as compared to tenofovir in rural Africa: preliminary data from the CART-1 study.

INTRODUCTION: Due to its side effects stavudine (D4T) has been replaced by zidovudine (AZT) and tenofovir (TDF) in most low- and middle-income countries (LMICs). In 2014 about 38% of adult first-line regimens contain AZT and 62% TDF [1]. Whereas the unfavourable metabolic outcomes of D4T in comparison to TDF have been described extensively, studies from LMICs comparing metabolic profiles between patients on AZT and TDF are scarce. Given the high number of patients in LMICs still taking AZT, data on their metabolic profile are needed. We present rates of metabolic syndrome (MS) in adult patients taking either AZT- or TDF-containing first-line, non-nucleoside reverse transcriptase (NNRTI)-based regimens. MATERIALS AND METHODS: Data derived from a cross-sectional multi-disease screening conducted in ten facilities in two rural districts of Lesotho, Southern Africa [2]. Patients were eligible if aged ≥25 years and on NNRTI-containing first-line ART ≥6 months. The MS definition for Africa of the International Diabetes Federation was applied [3]. Assessed potential predictors for MS were age, time on ART, virologic suppression, body-mass index (BMI), alcohol consumption, wealth quintile, NNRTI (nevirapine (NVP) or Efavirenz (EFV)), history of previous D4T exposure and ART-backbone (AZT or TDF). Statistical analyses - stratified for sex - comprised univariate logistic regression for each predictor variable with subsequent construction of a multivariate model including all predictors with an association to MS at a significance level<0.1 in univariate analysis. RESULTS: Out of 1026 patients, 660 (64.3%) were female. MS prevalence was 9.8% (95% CI 6.9-13.4) in men and 22.9% (19.7-26.3) in women. In women, aged ≥35 years, AZT-backbone, NVP-base, BMI ≥25kg/m2 and taking ART for ≥4.5 years were associated with MS in univariate analysis. In the multivariate model only AZT (adjusted odds-ratio: 2.2, 95% CI 1.4-3.6; p=0.001) and BMI ≥25kg/m2 (9.8; 2.8-34.1, p<0.001) were associated with MS. For men, age, higher wealth quintile, history of D4T exposure and BMI were associated with MS in univariate analysis. In the multivariate model only a BMI ≥25kg/m2 was associated with MS (8.9; 3.8-20.9, p<0.001). CONCLUSIONS: In rural Lesotho, Southern Africa, the use of AZT instead of TDF among women who are on ART for ≥6 months predisposes to the development of metabolic syndrome. Given that, still 38% of first-line regimens in LMIC contain AZT, this finding needs to be verified in other settings in Sub-Saharan Africa.

Outcomes of antiretroviral treatment programmes in rural Lesotho: health centres and hospitals compared.

INTRODUCTION: Lesotho was among the first countries to adopt decentralization of care from hospitals to nurse-led health centres (HCs) to scale up the provision of antiretroviral therapy (ART). We compared outcomes between patients who started ART at HCs and hospitals in two rural catchment areas in Lesotho. METHODS: The two catchment areas comprise two hospitals and 12 HCs. Patients ≥16 years starting ART at a hospital or HC between 2008 and 2011 were included. Loss to follow-up (LTFU) was defined as not returning to the facility for ≥180 days after the last visit, no follow-up (no FUP) as not returning after starting ART, and retention in care as alive and on ART at the facility. The data were analysed using logistic regression, competing risk regression and Kaplan-Meier methods. Multivariable analyses were adjusted for sex, age, CD4 cell count, World Health Organization stage, catchment area and type of ART. All analyses were stratified by gender. RESULTS: Of 3747 patients, 2042 (54.5%) started ART at HCs. Both women and men at hospitals had more advanced clinical and immunological stages of disease than those at HCs. Over 5445 patient-years, 420 died and 475 were LTFU. Kaplan-Meier estimates for three-year retention were 68.7 and 69.7% at HCs and hospitals, respectively, among women (p=0.81) and 68.8% at HCs versus 54.7% at hospitals among men (p<0.001). These findings persisted in adjusted analyses, with similar retention at HCs and hospitals among women (odds ratio (OR): 0.89, 95% confidence interval (CI): 0.73-1.09) and higher retention at HCs among men (OR: 1.53, 95% CI: 1.20-1.96). The latter result was mainly driven by a lower proportion of patients LTFU at HCs (OR: 0.68, 95% CI: 0.51-0.93). CONCLUSIONS: In rural Lesotho, overall retention in care did not differ significantly between nurse-led HCs and hospitals. However, men seemed to benefit most from starting ART at HCs, as they were more likely to remain in care in these facilities compared to hospitals.

A clinical prediction score in addition to WHO criteria for anti-retroviral treatment failure in resource-limited settings--experience from Lesotho.

OBJECTIVE: To assess the positive predictive value (PPV) of a clinical score for viral failure among patients fulfilling the WHO-criteria for anti-retroviral treatment (ART) failure in rural Lesotho. METHODS: Patients fulfilling clinical and/or immunological WHO failure-criteria were enrolled. The score includes the following predictors: Prior ART exposure (1 point), CD4-count below baseline (1), 25% and 50% drop from peak CD4-count (1 and 2), hemoglobin drop≥1 g/dL (1), CD4 count<100/µl after 12 months (1), new onset papular pruritic eruption (1), and adherence<95% (3). A nurse assessed the score the day blood was drawn for viral load (VL). Reported confidence intervals (CI) were calculated using Wilsons method. RESULTS: Among 1'131 patients on ART ≥ 6 months, 134 (11.8%) had immunological and/or clinical failure, 104 (78%) had blood drawn (13 died, 10 lost to follow-up, 7 did not show up). From 92 (88%) a result could be obtained (2 samples hemolysed, 10 lost). Out of these 92 patients 47 (51%) had viral failure (≥ 5000 copies), 27 (29%) viral suppression (<40) and 18 (20%) intermediate viremia (40-4999). Overall, 20 (22%) had a score ≥ 5. A score ≥ 5 had a PPV of 100% to detect a VL>40 copies (95%CI: 84-100), and of 90% to detect a VL ≥ 5000 copies (70-97). Within the score, adherence<95%, CD4-count<100/µl and papular pruritic eruption were the strongest single predictors. Among 47 patients failing, 8 (17%) died before or within 4 weeks after being switched. Overall mortality was 4 (20%) among those with score ≥ 5 and 4 (5%) if score<5 (OR 4.3; 95%CI: 0.96-18.84, p = 0.057). CONCLUSION: A score ≥ 5 among patients fulfilling WHO-criteria had a PPV of 100% for a detectable VL and 90% for viral failure. In settings without regular access to VL-testing, this PPV may be considered high enough to switch this patient-group to second-line treatment without confirmatory VL-test.

Outcomes of antiretroviral treatment programs in rural Southern Africa.

BACKGROUND: Data on outcomes of antiretroviral treatment (ART) programs in rural sub-Saharan African are scarce. We describe early losses and long-term outcomes in 6 rural programs in Southern Africa with limited access to viral load monitoring and second-line ART. METHODS: Patients aged ≥16 years starting ART in 2 programs each in Zimbabwe, Mozambique, and Lesotho were included. We evaluated risk factors for no follow-up after starting ART and mortality and loss to follow-up (LTFU) over 3 years of ART, using logistic regression and competing risk models. Odds ratios and subdistribution hazard ratios, adjusted for gender, age category, CD4 category, and World Health Organization stage at start of ART are reported. RESULTS: Among 7725 patients, 449 (5.8%) did not return after initiation of ART. During 9575 person-years, 698 (9.6%) of those with at least 1 follow-up visit died, and 1319 (18.1%) were LTFU. At 3 years, the cumulative incidence of death and LTFU were 12.5% (11.5%-13.5%) and 25.4% (24.0%-26.9%), respectively, with important differences between countries as follows: in Zimbabwe 75.1% (72.8%-77.3%) were alive and on ART at 3 years compared with 55.4% (52.8%-58.0%) in Lesotho and 51.6% (48.0%-55.2%) in Mozambique. In all settings, young age and male gender predicted LTFU, whereas advanced clinical stage and low baseline CD4 counts predicted death. CONCLUSIONS: In African ART programs with limited access to second-line treatment, mortality, and LTFU are high in the first 3 years of ART. Low retention in care is a major threat to the sustainability of ART delivery in Southern Africa, particularly in rural sites.