Antiretroviral Therapy In Zambia Research Articles

Body Mass Index Status Determines Absolute CD4+ Count in Adult HIV/AIDS Patients on Antiretroviral Therapy in Zambia

Objective: To determine if Body Mass Index would predict absolute CD4 count to suggest its contribution towards immune augmentation and viral suppression among the victims of HIV/AIDS. Design and methods: The researchers conducted a cross sectional-quantitative study involving 174 adult HIV/AIDS patient participants who were enrolled over a period of 18 months at Ndola Teaching Hospital in Ndola, Zambia. Participants were subjected to clinical assessments with anthropometry, viral load, CD4+ count and plasma fat measurements at control and repeated on a follow-up visit. The Wilcoxon rank sum analysis was used to analyze the quantitative parameters while the Chi square analysis was applied to analyze nominal variables by sex respectively. The main research question was addressed by establishing the association between Body Mass Index and CD4 count, adjusted for potential confounders using the multiple linear regression model. Results: The BMI was within the normal range for both male and female gender, although notably higher in the females [median=22.9; interquartile (20.4,27.5) kg/m2] than in the males [median=21; interquartile (18.8,23.9) kg/m2], p=0.01. The median CD4+ counts were found to be lower than the lower limit of the normal for the laboratory reference range of (500-1500 cells/ul) in both genders. There was a positive correlation between CD4+ count and the BMI in both unadjusted [Coef=0.05; 95%, CI(0.03,-0.08), p=0.00] and adjusted [Coef=0.04; 95% CI(0.00,0.07), p=0.03] models respectively. Similarly, there was a positive correlation between CD4+ count and the BMI [Coef=0.04; 95% CI(0.00,0.08), p=0.04], reported in the adjusted model for the female gender. Conclusion: Body mass index was found to be positively correlated with absolute CD4 count, and more substantively so by female gender.

Kaposi’s Sarcoma Trends in the Era of Highly Active Antiretroviral Therapy in Zambia

AIDS-related Kaposi’s Sarcoma (KS) is a multi-centric angiogenic neoplastic proliferation predominantly seen in individuals with Human Immune Virus (HIV-1) infection and men who have sex with men. Although the incidences of aggressive KS have reduced following the introduction of Highly Active Antiretroviral Therapy (HAART) in the treatment of HIV infection, the effect of HAART rollout in relation to population KS incidence in Zambia remains unclear as cases of the malignancy have continued to be reported. This study, investigated the trends of KS in the era of HAART in Zambia. The researchers conducted a retrospective cross-sectional study. Three hundred and twentycases of HIV-infected individuals on HAART that developed KS between 2008 and 2017 were reviewed. Data was retrieved from the Zambia National Cancer Registry (ZNCR). Of the records reviewed, the researchers observed a sharp increase in KS cases from 5.6 per cent in 2008 to 21.2 per cent in 2014; from 2015 to 2017, there was a general decline in KS cases countrywide in both sexes from 13.1 per cent to 9.4 per cent. KS was more prevalent in Lusaka Province, while Western Province had the least number of cases. For each province, there were more males affected by KS than females. The researchers further observed that 19.1 per cent of the cases reviewed developed KS while on HAART, while 80.9 per cent developed KS before the commencement of HAART. The age group with the highest number of KS cases was 21-40 years, while the age group ≥ 80 had the least number of cases. Our data has shown that although there has been a general decline in KS cases across the ten provinces of Zambia in recent years, more efforts are still required to mitigate AIDS-related KS incidence and improve KS prognosis. There is a need to encourage efforts aimed at HIV infection prevention, wide coverage of HAART across the country, and KS awareness and screening.

Evaluation of kidney function among people living with HIV initiating antiretroviral therapy in Zambia.

As the response to the HIV epidemic in sub-Saharan Africa continues to mature, a growing number of people living with HIV (PLHIV) are aging and risk for non-communicable diseases increases. Routine laboratory tests of serum creatinine have been conducted to assess HIV treatment (ART) suitability. Here we utilize those measures to assess kidney function impairment among those initiating ART. Identification of non-communicable disease (NCD) risks among those in HIV care creates opportunity to improve public health through care referral and/or NCD/HIV care integration. We estimated glomerular filtration rates (eGFR) using routinely collected serum creatinine measures among a cohort of PLHIV with an HIV care visit at one of 113 Centre for Infectious Disease Research Zambia (CIDRZ) supported sites between January 1, 2011 and December 31, 2017, across seven of the ten provinces in Zambia. We used mixed-effect Poisson regression to assess predictors of eGFR <60ml/min/1.73m2 allowing random effects at the individual and facility level. Additionally, we assessed agreement between four eGFR formulae with unadjusted CKD-EPI as a standard using Scott/Fleiss method across five categories of kidney function. A total of 72,933 observations among 68,534 individuals met the inclusion criteria for analysis. Of the 68,534, the majority were female 41,042 (59.8%), the median age was 34 (interquartile range [IQR]: 28-40), and median CD4 cell count was 292 (IQR: 162-435). The proportion of individuals with an eGFR <60ml/min/1.73m2 was 6.9% (95% CI: 6.7-7.1%) according to the unadjusted CKD-EPI equation. There was variation in agreement across eGFR formulas considered compared to unadjusted CKD-EPI (χ2 p-value <0.001). Estimated GFR less than 60ml/min/1.73m2, per the unadjusted CKD-EPI equation, was significantly associated with age, sex, body mass index, and blood pressure. Using routine serum creatinine measures, we identified a significant proportion of individuals with eGFR indicating moderate or great kidney function impairment among PLHIV initiating ART in Zambia. It is possible that differentiated service delivery models could be developed to address this subset of those in HIV care with increased risk of chronic kidney disease.

Water Access and Adherence Intention Among HIV-Positive Pregnant Women and New Mothers Receiving Antiretroviral Therapy in Zambia.

BackgroundMother-to-infant transmission of HIV is a major problem in Sub-Saharan Africa despite free or subsidized antiretroviral treatment (ART), but is significantly reduced when mothers adhere to ART. Because potable water access is limited in low-resource countries, we investigated water access and ART adherence intention among HIV-positive pregnant women and new mothers in Zambia.MethodsOur convenience sample consisted of 150 pregnant or postpartum women receiving ART. Descriptive statistics compared type of water access by low and high levels of ART adherence intention.ResultsMost (71%) had access to piped water, but 36% of the low-adherence intention group obtained water from a well, borehole, lake or stream, compared to only 22% of the high-adherence intention group. The low-adherence intention group was more rural (62%) than urban (38%) women but not statistically significant [unadjusted Prevalence Ratio (PR) 0.73, 95% CI: 0.52–1.02; adjusted PR 1.06, 95% CI: 0.78–1.45].ConclusionProviding potable water may improve ART adherence. Assessing available water sources in both rural and urban locations is critical when educating women initiating ART.

Prevalence of low high-density lipoprotein among young adults receiving antiretroviral therapy in Zambia: An opportunity to consider non-communicable diseases in resource-limited settings.

BackgroundWith the introduction of effective antiretroviral therapy (ART), people living with HIV (PLWH) are surviving longer and are at risk for developing metabolic abnormalities that contribute to cardiovascular disease (CVD). In Sub-Saharan Africa (SSA), there is a paucity of epidemiological data on lipid profiles among young adults receiving ART. This study aimed to estimate the prevalence of low high-density lipoprotein cholesterol (HDL-c), a cardioprotective lipid class, and whether it differed by age among adults on ART in Livingstone, Zambia.MethodsFrom April to December 2019, we conducted a cross-sectional study of 597 PLWH [n = 58 aged 18–24 years (young adults); n = 539 aged ≥25 years (adults)] on ART for ≥6 months. Data collected included demographic and lifestyle information, anthropometrics, viral load (VL), CD4 count, blood pressure, lipid profiles and fasting/random blood glucose. Clinical measures were defined as: low HDL-c [<1.0 mmol/L for men, <1.3 for women], increased waist circumference (WC) [≥94 cm for men, ≥80 cm for women], high triglycerides (TG) [≥1.7 mmol/l], and virological failure (VF) [VL ≥1000 copies/μl]. We used logistic regression to examine the association between age and low HDL-c after adjusting for multiple variables.ResultsAmong the young adults, 60% (35/58) were women, median (25th, 75th percentile) age 21 years (18, 23), and median time on ART 116 months (60, 144). Among adults, 63% (342/539) were women, median age 46 years (40, 53) and median time on ART 108 months (60, 144). Young adults had a lower CD4 count compared to adults (median, 492 vs. 568 cells/μL, p = 0.010) and higher prevalence of VF (29% vs. 17%, p = 0.016). In young adults, prevalence of low HDL-c was significantly higher than in adults (63 vs. 38%, p<0.001). A high proportion of young adults (75%) and adults (58%) with low HDL-c were on dolutegravir (DTG)-based ART regimens. After adjusting for sex, duration on ART, WC, body mass index, ART regimen, VF, CD4 count, low density lipoprotein cholesterol, blood pressure and smoking, young adults were significantly more likely than adults to have low HDL-c (odds ratio 2.93; 95% confidence interval 1.46–5.86).ConclusionLow HDL-c is highly prevalent among young adult with HIV in SSA independent of other risk factors for metabolic derangements. Lipid abnormalities among young PLWH may contribute to the early development of cardiovascular diseases in this population. This highlights the need to consider low HDL-c in the quest to reduce CVD risk among young adults on ART in SSA.

Community-based delivery of HIV treatment in Zambia: costs and outcomes.

Objective:The aim is to determine the total annual cost per patient treated and total cost per patient retained on antiretroviral therapy in Zambia in conventional care in facilities and across community-based differentiated service delivery (DSD) models.Design:Economic evaluation was conducted using retrospective electronic record review.Twenty healthcare facilities (13 with DSD models and 7 as comparison sites) in six of Zambia's 10 provinces were considered.Methods:All individuals on antiretroviral therapy (ART) >18 years old at the study sites were enrolled in a DSD model or conventional care by site type, respectively, with at least 12 months of follow-up data. Accessing care through DSD models [community adherence groups (CAGs), urban adherence groups (UAGs), home ART delivery and care, and mobile ART services] or facility-based conventional care with 3-monthly visits. Total annual cost per patient treated and the annual cost per patient retained in care 12 months after model enrolment. Retention in care was defined as attending a clinic visit at 12 months ± 3 months.Results:The DSD models assessed cost more per patient/year than conventional care. Costs ranged from an annual $116 to $199 for the DSD models, compared with $100 for conventional care. CAGs and UAGs increased retention by 2 and 14%, respectively. All DSD models cost more per patient retained at 12 months than conventional care. The CAG had the lowest cost/patient retained for DSD models ($140–157).Conclusions:Although they achieve equal or improved retention in care, out-of-facility models of ART were more expensive than conventional care.

The Lazarus Effect and the Labour Market: Evidence from At-Scale Antiretroviral Therapy in Zambia

Abstract Between 2000 and 2015, access to life-saving antiretroviral therapy (ART) in sub-Saharan Africa increased from virtually 0% to approximately 40% coverage. Despite the promise of ART to improve health, a variety of supply- and demand-side factors suggest at-scale ART may not improve employment outcomes. To measure the causal effect of ART on employment outcomes, I use triple-difference regression analysis, exploiting spatial, temporal and demographic variation in intensity of ART exposure during scale-up in Zambia. My results suggest that local ART introduction increased employment of likely HIV+ adults by eight percentage points, or approximately 15% relative to the sample mean. Cash employment and employment for no pay—the first and second largest employment categories in Zambia, respectively—each comprised roughly one-half of the employment gains. Temporal and spatial heterogeneity analyses support a causal interpretation of the results. These findings appear to be the first at-scale quasi-experimental evidence suggesting that ART, the single largest item in many countries’ foreign health aid budgets, can improve employment outcomes among the targeted.

Survival of Children Living With HIV on Art in Zambia: A 13-Years Retrospective Cohort Analysis.

Background: Research conducted before the introduction of anti-retroviral therapy (ART), showed that the majority of children living with HIV (CLHIV) would die before their second birthday. In Zambia, ART was rolled out to the public health system in 2004 with subsequent improved survival in CLHIV. However, the survival rates of CLHIV on ART in Zambia since 2004 have not been extensively documented. We assessed survival experiences and the factors associated with survival in CLHIV on ART in Zambia.Methods: We conducted a retrospective cohort analysis of CLHIV (aged up to 15 years) using routinely collected data from health facilities across Zambia, over 13 years to ascertain mortality rates. We explored survival factors using Cox regression giving adjusted hazard ratios (AHR) and 95% confidence intervals (95% CI). Nelson Aalen estimates were used to show the cumulative hazards of mortality for different levels of explanatory factors.Results: A total of 65,448 eligible children, were initiated on ART between 2005 and 2018, of which 33,483 (51%) where female. They contributed a total survival time of 275,715-person years at risk during which 3,265 children died which translated into an incidence rate of 1.1 deaths per 100 person-years during the review period. Mortality rates were highest in children in the first year of life (Mortality rate 2.24; 95% CI = 2.08–2.42) and during the first year on ART (Mortality rate 3.82 95% CI = 3.67–3.98). Over 50% of the children had been on ART for 5–10 years by 2018, and they had the lowest risk of mortality compared to children who had been on ART for <5 years.Conclusions: Children with HIV in Zambia are surviving much longer than was predicted before ART was introduced 14 years ago. This key finding adds to the literature on analysis of survival in CLHIV in low income settings like Zambia. However, this survival is dependent on the age at which ART is initiated and the time on ART highlighting the need to increase investments in early infant diagnosis (EID) to ensure timely HIV testing and ART initiation for CLHIV.

Types of episodic disability among people living with HIV in Zambia

ABSTRACT HIV is increasingly recognized as a chronic illness which may result in episodic disability related to the effects of the virus, side effects of medication, co-morbidities and consequences of aging. Little is known about the episodic disability experiences of people living long-term with HIV in resource-limited countries, which is best understood by following people over time. This qualitative longitudinal study examined the episodic disability experiences and the applicability of four types of episodic disability among people living with HIV and on anti-retroviral therapy in Zambia. We interviewed 31 men and women living with HIV on 3 occasions at 6-month intervals (total of 93 interviews) examining the processes of change over time. We used disability models to inform the interviews exploring impairments/symptoms, activity limitations and participation restrictions. Longitudinal analyses of transcribed interviews confirmed the applicability of four types over time: stable, increasing disability, decreasing disability and significant fluctuations. Analyses highlighted the extent to which determinants of health contributed to the disability experienced. The use of disability models revealed the importance of environmental and social influences on disability and quality of life. The indicators of the type of episodic disability could be used clinically to help understand the nature and potential triggers of the episodes.

High Rates of Hepatitis B Virus (HBV) Functional Cure Among Human Immunodeficiency Virus-HBV Coinfected Patients on Antiretroviral Therapy in Zambia.

Among 284 human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected adults starting tenofovir-based antiretroviral therapy (ART) in Zambia, median baseline CD4+ count was 202 cells/mm3 and 41.6% were hepatitis B e-antigen positive. Within 2 years of therapy, 29 (10.2%) participants experienced HBV functional cure (confirmed loss of hepatitis B surface antigen). In multivariable analysis, baseline CD4 count <350 cells/mm3, female sex, and lower baseline HBV deoxyribonucleic acid were associated with increased odds of functional cure. Immune recovery during HIV-HBV treatment with ART may drive higher rates of functional cure than during HBV monoinfection treatment. Understanding the mechanisms underlying this phenomenon could inform immunomodulatory therapies for HBV cure.

Correction: Retention and viral suppression in a cohort of HIV patients on antiretroviral therapy in Zambia: Regionally representative estimates using a multistage-sampling-based approach

[This corrects the article DOI: 10.1371/journal.pmed.1002811.].

Predictors of loss to follow-up among children on long-term antiretroviral therapy in Zambia (2003\u20132015)

BackgroundRetention in care is critical for children living with HIV taking antiretroviral therapy (ART). Loss to follow-up (LTFU) is high in HIV treatment programs in resource limited settings. We estimated the cumulative incidence of LTFU and identified associated risk factors among children on ART at Livingstone Central Hospital (LCH), Zambia.MethodsUsing a retrospective cohort study design, we abstracted data from medical records of children who received ART between 2003 and 2015. Loss to follow-up was defined as no clinical and pharmacy contact for at least 90 days after the child missed their last scheduled clinical visit. Non-parametric competing risks models were used to estimate the cumulative incidence of death, LTFU and transfer. Cause-specific Cox regression was used to estimate the hazard ratios of the risk factors of LTFU.ResultsA total of 1039 children aged 0–15 years commenced ART at LCH between 2003 and 2015. Median duration of follow-up was 3.8 years (95% CI: 1.2–6.5), median age at ART initiation was 3.6 years (IQR: 1.3–8.6), 179 (17%) started treatment during their first year of life. At least 167 (16%) were LTFU and we traced 151 (90%). Of those we traced, 39 (26%) had died, 71 (47%) defaulted, 20 (13%) continued ART at other clinics and 21 (14%) continued treatment with gaps. The cumulative incidence of LTFU for the entire cohort was 2.7% (95% CI: 1.9–3.9) at 3 months, 4.1% (95% CI: 2.9–5.4) at 6 months and 14.1% (95% CI: 12.4–16.9) after 5 years on ART. Associated risk factors were: 1) non-disclosure of HIV status at baseline, aHR = 1.9 (1.2–2.9), 2) No phone ownership, aHR = 2.1 (1.6–2.9), 3) starting treatment between 2013 to 2015, aHR = 5.6 (2.2–14.1).ConclusionAmong the children LTFU mortality and default were substantially high. Children who started treatment in recent years (2013–2015) had the highest hazard of LTFU. Lack of access to a phone and non-disclosure of HIV-status to the index child was associated with higher hazards of LTFU. We recommend re-enforcement of client counselling and focused follow-up strategies using modern technology such as mobile phones as adjunct to current approaches.

Retention and viral suppression in a cohort of HIV patients on antiretroviral therapy in Zambia: Regionally representative estimates using a multistage-sampling-based approach.

BackgroundAlthough the success of HIV treatment programs depends on retention and viral suppression, routine program monitoring of these outcomes may be incomplete. We used data from the national electronic medical record (EMR) system in Zambia to enumerate a large and regionally representative cohort of patients on treatment. We traced a random sample with unknown outcomes (lost to follow-up) to document true care status and HIV RNA levels.Methods and findingsOn 31 July 2015, we selected facilities from 4 provinces in 12 joint strata defined by facility type and province with probability proportional to size. In each facility, we enumerated adults with at least 1 clinical encounter after treatment initiation in the previous 24 months. From this cohort, we identified lost-to-follow-up patients (defined as 90 or more days late for their last appointment), selected a random sample, and intensively reviewed their records and traced them via phone calls and in-person visits in the community. In 1 of 4 provinces, we also collected dried blood spots (DBSs) for plasma HIV RNA testing. We used inverse probability weights to incorporate sampling outcomes into Aalen–Johansen and Cox proportional hazards regression to estimate retention and viremia. We used a bias analysis approach to correct for the known inaccuracy of plasma HIV RNA levels obtained from DBSs. From a total of 64 facilities with 165,464 adults on ART, we selected 32 facilities with 104,966 patients, of whom 17,602 (17%) were lost to follow-up: Those lost to follow-up had median age 36 years, 60% were female (N = 11,241), they had median enrollment CD4 count of 220 cells/μl, and 38% had WHO stage 1 clinical disease (N = 10,690). We traced 2,892 (16%) and found updated outcomes for 2,163 (75%): 412 (19%) had died, 836 (39%) were alive and in care at their original clinic, 457 (21%) had transferred to a new clinic, 255 (12%) were alive and out of care, and 203 (9%) were alive but we were unable to determine care status. Estimates using data from the EMR only suggested that 42.7% (95% CI 38.0%–47.1%) of new ART starters and 72.3% (95% CI 71.8%–73.0%) of all ART users were retained at 2 years. After incorporating updated data through tracing, we found that 77.3% (95% CI 70.5%–84.0%) of new initiates and 91.2% (95% CI 90.5%–91.8%) of all ART users were retained (at original clinic or transferred), indicating that routine program data underestimated retention in care markedly. In Lusaka Province, HIV RNA levels greater than or equal to 1,000 copies/ml were present in 18.1% (95% CI 14.0%–22.3%) of patients in care, 71.3% (95% CI 58.2%–84.4%) of lost patients, and 24.7% (95% CI 21.0%–29.3%). The main study limitations were imperfect response rates and the use of self-reported care status.ConclusionsIn this region of Zambia, routine program data underestimated retention, and the point prevalence of unsuppressed HIV RNA was high when lost patients were accounted for. Viremia was prevalent among patients who unofficially transferred: Sustained engagement remains a challenge among HIV patients in Zambia, and targeted sampling is an effective strategy to identify such gaps in the care cascade and monitor programmatic progress.

Efficacy and safety of artemether\u2013lumefantrine as treatment for Plasmodium falciparum uncomplicated malaria in adult patients on efavirenz-based antiretroviral therapy in Zambia: an open label non-randomized interventional trial

BackgroundHIV-infected individuals on antiretroviral therapy (ART) require treatment with artemisinin-based combination therapy (ACT) when infected with malaria. Artemether–lumefantrine (AL) is the most commonly used ACT for treatment of falciparum malaria in Africa but there is limited evidence on the safety and efficacy of AL in HIV-infected individuals on ART, among whom drug–drug interactions are expected. Day-42 adequate clinical and parasitological response (ACPR) and incidence of adverse events was assessed in HIV-infected individuals on efavirenz-based ART with uncomplicated falciparum malaria treated with AL.MethodsA prospective, open label, non-randomized, interventional clinical trial was conducted at St Paul’s Hospital in northern Zambia, involving 152 patients aged 15–65 years with uncomplicated falciparum malaria, who were on efavirenz-based ART. They received a 3-day directly observed standard treatment of AL and were followed up until day 63. Day-42 polymerase chain reaction (PCR)-corrected ACPRs (95% confidence interval [CI]) were calculated for the intention-to-treat population.ResultsEnrolled patients had a baseline geometric mean (95% CI) parasite density of 1108 (841–1463) parasites/µL; 16.4% (25/152) of the participants had a recurrent malaria episode by day 42. However, PCR data was available for 17 out of the 25 patients who had malaria recurrence. Among all the 17 patients, PCR findings demonstrated malaria re-infection, making the PCR-adjusted day-42 ACPR 100% in the 144 patients who could be evaluated. Even when eight patients with missing PCR data were considered very conservatively as failures, the day-42 ACPR was over 94%. None of the participants, disease or treatment characteristics, including day-7 lumefantrine concentrations, predicted the risk of malaria recurrence by day 42. AL was well tolerated following administration. There were only two cases of grade 3 neutropaenia and one serious adverse event of lobar pneumonia, none of which was judged as probably related to intake of AL.ConclusionsAL was well tolerated and efficacious in treating uncomplicated falciparum malaria in HIV co-infected adults on efavirenz-based ART. However, a higher than anticipated proportion of participants experienced malaria re-infection, which highlights the need for additional malaria prevention measures in this sub-population after treatment with AL.Trial registration Pan African Clinical Trials Registry (PACTR): PACTR201311000659400. Registered on 4 October 2013. https://pactr.samrc.ac.za/Search.aspx

Effects of adult health interventions at scale on children’s schooling: Evidence from antiretroviral therapy in Zambia

In 2007, approximately one in five children in Zambia lived with an HIV positive adult. We identify the effect of adult antiretroviral therapy (ART) availability at scale on children’s educational outcomes by combining data on the expansion of ART availability with two national household surveys that include HIV testing. Through a triple difference specification, we find that the availability of ART increased the likelihood that children in households with HIV positive household heads started school on time and were the appropriate grade-for-age. Two mechanisms were likely decreased incidental infections in the household and related care giving duties.

Differentiated Care Preferences of Stable Patients on Antiretroviral Therapy in Zambia: A Discrete Choice Experiment.

Although differentiated service delivery (DSD) models for stable patients on antiretroviral therapy (ART) offer a range of health systems innovations, their comparative desirability to patients remains unknown. We conducted a discrete choice experiment to quantify service attributes most desired by patients to inform model prioritization. Between July and December 2016, a sample of HIV-positive adults on ART at 12 clinics in Zambia were asked to choose between 2 hypothetical facilities that differed across 6 DSD attributes. We used mixed logit models to explore preferences, heterogeneity, and trade-offs. Of 486 respondents, 59% were female and 85% resided in urban locations. Patients strongly preferred infrequent clinic visits [3- vs. 1-month visits: β (ie, relative utility) = 2.84; P < 0.001]. Milder preferences were observed for waiting time for ART pick-up (1 vs. 6 hours.; β = -0.67; P < 0.001) or provider (1 vs. 3 hours.; β = -0.41; P = 0.002); "buddy" ART collection (β = 0.84; P < 0.001); and ART pick-up location (clinic vs. community: β = 0.35; P = 0.028). Urban patients demonstrated a preference for collecting ART at a clinic (β = 1.32, P < 0.001), and although most rural patients preferred community ART pick-up (β = -0.74, P = 0.049), 40% of rural patients still preferred facility ART collection. Stable patients on ART primarily want to attend clinic infrequently, supporting a focus in Zambia on optimizing multimonth prescribing over other DSD features-particularly in urban areas. Substantial preference heterogeneity highlights the need for DSD models to be flexible, and accommodate both setting features and patient choice in their design.

Evolution of HIV-1 drug resistance after virological failure of first-line antiretroviral therapy in Lusaka, Zambia.

HIV viral load (VL) and resistance testing are limited in sub-Saharan Africa, so individuals may have prolonged time on failing first-line antiretroviral therapy (ART). Our objective was to describe the evolution of drug resistance mutations among adults failing first-line ART in Zambia. We analysed data from a trial of VL monitoring in Lusaka, Zambia. From 2006 to 2011, 12 randomized sites provided either routine VL monitoring (intervention) or discretionary (control) after ART initiation. Samples were collected prospectively following the same schedule in each arm but analysed retrospectively in the control group. For those with virological failure (VF; >400 copies/ml), HIV genotyping was performed retrospectively on baseline (BL) and on all subsequent specimens until censored due to study completion, withdrawal or death. Of 1,973 enrollees, 165 (8.4%) developed VF. 464 genotype results were available including 132 (80%) at BL, 116 (70%) at VF and 125 (76%) had at least one result between VF and censoring. Major nucleoside reverse transcriptase inhibitor (NRTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations increased from 26% (BL) to 82% (VF) to 89% at last genotype (LG). M184 mutations increased from 2% to 59% to 71%; K65R from 2% to 11% to 13%; 2 or more thymidine analogue mutations from 1% to 3% to 12%. Among those on a failing tenofovir disoproxil fumarate (TDF)-based regimen, TDF resistance increased from 42% to 58%. We found substantial resistance to NRTIs and NNRTIs at VF with incremental increases after VF while still on a failing first-line ART; this resistance may compromise attainment of the UNAIDS 90-90-90 goals.

Survival of people on antiretroviral treatment in Zambia: a retrospective cohort analysis of HIV clients on ART.

IntroductionProvision of free anti-retroviral therapy in Zambia started in June 2004. There were only 15,000 people on treatment as at December that year, mainly due to lack of access. This number rose to 580,000 people as at December 2013. The general objective of this study was to determine survival of people on ART and to examine associated predictors for survival.MethodsThe study included ART patients enrolled between the year 2002 and 2013 (n=10,395) in 285 health facilities in Zambia. Patient files were analyzed retrospectively. The study used Kaplan Meier and Cox-proportional hazard models to describe the relationship between lost to follow up and age, sex, baseline CD4 cell count and weight.ResultsResults showed that lost to follow up accounted for 90% of the clients that had dropped out, while 10% was to deaths. Low baseline CD4 count (p-value 0.001, HR 0.9994, (95% CI 0.9993, 0.9996) at initiation was associated with lost to follow up together with weight at initiation (p-value 0.031, HR 0.9987 at 95% CI (0.9975, 0.9998)) of ART.ConclusionThis study has demonstrated that lost to follow up is a substantial contributing factor to drop outs among HIV patients on treatment. Strengthening of community treatment supporters especially immediate family members in emphasizing to the client the need to continue treatment is necessary. The health facility could do more in emphasizing the importance of treatment especially in the initial stages. Further, in order to reduce opportunistic infections and probable deaths during treatment, cotrimoxazole prophylaxis should be maintained so as to raise the CD4 levels. Improved nutritional assessment and counseling to boost the nutritional status of the clients throughout should be encouraged.

T-Cell Subsets Predict Mortality in Malnourished Zambian Adults Initiating Antiretroviral Therapy.

ObjectiveTo estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART), and to assess the impact of a nutritional intervention on T-cell subsets.MethodsThis was a sub-study of a randomised clinical trial of a nutritional intervention for malnourished adults initiating ART. Participants in a randomised controlled trial (NUSTART trial) were enrolled between April and December 2012. Participants received lipid-based nutritional supplement either with or without additional vitamins and minerals. Immunophenotyping was undertaken at baseline and, in survivors, after 12 weeks of ART to characterize T-cell subsets using the markers CD3, CD4, CD8, CD45RA, CCR7, CD28, CD57, CD31, α4β7, Ki67, CD25 and HLA-DR. Univariate and multivariate survival analysis was performed, and responses to treatment were analysed using the Wicoxon rank-sum test.ResultsAmong 181 adults, 36 (20%) died by 12 weeks after starting ART. In univariate analysis, patients who died had fewer proliferating, more naïve and fewer gut homing CD4+ T-cells compared to survivors; and more senescent and fewer proliferating CD8+ T-cells. In a multivariate Cox regression model high naïve CD4+, low proliferating CD4+, high senescent CD8+ and low proliferating CD8+ subsets were independently associated with increased risk of death. Recent CD4+ thymic emigrants increased less between recruitment and 12 weeks of ART in the intervention group compared to the control group.ConclusionsSpecific CD4+ T-cell subsets are of considerable prognostic significance for patients initiating ART in Zambia, but only thymic output responded to this nutritional intervention.

Retention in care, resource utilization, and costs for adults receiving antiretroviral therapy in Zambia: a retrospective cohort study

BackgroundOf the estimated 800,000 adults living with HIV in Zambia in 2011, roughly half were receiving antiretroviral therapy (ART). As treatment scale up continues, information on the care provided to patients after initiating ART can help guide decision-making. We estimated retention in care, the quantity of resources utilized, and costs for a retrospective cohort of adults initiating ART under routine clinical conditions in Zambia.MethodsData on resource utilization (antiretroviral [ARV] and non-ARV drugs, laboratory tests, outpatient clinic visits, and fixed resources) and retention in care were extracted from medical records for 846 patients who initiated ART at ≥15 years of age at six treatment sites between July 2007 and October 2008. Unit costs were estimated from the provider’s perspective using site- and country-level data and are reported in 2011 USD.ResultsPatients initiated ART at a median CD4 cell count of 145 cells/μL. Fifty-nine percent of patients initiated on a tenofovir-containing regimen, ranging from 15% to 86% depending on site. One year after ART initiation, 75% of patients were retained in care. The average cost per patient retained in care one year after ART initiation was $243 (95% CI, $194-$293), ranging from $184 (95% CI, $172-$195) to $304 (95% CI, $290-$319) depending on site. Patients retained in care one year after ART initiation received, on average, 11.4 months’ worth of ARV drugs, 1.5 CD4 tests, 1.3 blood chemistry tests, 1.4 full blood count tests, and 6.5 clinic visits with a doctor or clinical officer. At all sites, ARV drugs were the largest cost component, ranging from 38% to 84% of total costs, depending on site.ConclusionsPatients initiate ART late in the course of disease progression and a large proportion drop out of care after initiation. The quantity of resources utilized and costs vary widely by site, and patients utilize a different mix of resources under routine clinical conditions than if they were receiving fully guideline-concordant care. Improving retention in care and guideline concordance, including increasing the use of tenofovir in first-line ART regimens, may lead to increases in overall treatment costs.