Lamivudine Concentration in Hair and Prediction of Virologic Failure and Drug Resistance among HIV Patients Receiving Free ART in China

BackgroundThe assessment of adherence to antiretroviral therapy (ART) is important in order to predict treatment outcomes. Lamivudine (3TC) is one of the most widely used NRTIs in China, but its concentrations in hair and association with virologic failure and drug resistance have not been studied.MethodsWe conducted a cross-sectional survey to investigate 3TC concentrations in hair as a predictor of virologic failure and drug resistance among HIV patients receiving free ART. We also compared the capacity of hair 3TC concentrations with self-reported adherence in predicting virologic responses. Hair 3TC concentrations were detected through the LC-MS/MS system.ResultsIn patients without HIV drug resistance (HIVDR), with a threshold hair 3TC concentration of 260 ng/g, the sensitivity and specificity in predicting virologic suppression were 76.9% and 89.9%, respectively. Some factors, including CD4⁺ cell counts, initial treatment regimens with 3TC, and current regimens with second-line drugs, influenced the association between hair 3TC concentrations and virologic suppression. In patients who experienced virologic failure with HIVDR, with a threshold of 180 ng/g, the sensitivity and specificity were 70.0% and 74.4%, respectively. Hair 3TC concentrations had higher sensitivity and specificity in predicting virologic failure and drug resistance than self-reported adherence.ConclusionsThe hair 3TC concentration was a stronger indicator than self-reported adherence in predicting virologic failure and drug resistance in HIV patients receiving free ART.     

Medication Possession Ratio Associated with Short-Term Virologic Response in Individuals Initiating Antiretroviral Therapy in Namibia

The visual-analogue scale (VAS), Likert item (rating scale), pills identification test (PIT), and medication possession ratio (MPR) provide estimates of antiretroviral therapy (ART) adherence which correlate with HIV viral suppression. These simple adherence measures are inexpensive and easy to administer; however, require validation and adjustment prior to implementation. The objective of this study was to define the optimal adherence assessment measure in Namibia to identify patients at risk for sub-optimal adherence and poor virologic response 6 months after ART initiation. We conducted a cross-sectional survey in HIV-infected adults receiving ART for 6–12 months prior to the adherence assessment. Adherence measures included 30-day VAS, 30-day Likert item, self-reported treatment interruptions, PIT, and MPR. Association of adherence measures with 6-month HIV-1 RNA level was assessed using two thresholds (1000 copies/mL and 5000 copies/mL). Adherence was assessed in 236 patients, mean age 37.3 years, 54% female. Mean adherence was 98.1% by 30-day VAS, 84.7% by 30-day Likert item, 97.0% by self-reported treatment interruptions, 90.6% by PIT, and 98.8% by MPR. Agreement between adherence measures was poor using kappa statistic. 76% had HIV-1 RNA <1000 copies/ml, and 88% had HIV-1 RNA <5000 copies/ml. MPR (continuous) was associated with viral suppression <5000 copies/ml (p = 0.036). MPR <75% was associated with virologic failure at ≥5000 copies/ml with OR 3.89 (1.24, 12.21), p = 0.013. Adherence was high with all measures. Only MPR, was associated with short-term virologic response, suggesting its cross-culturally utility for early identification of patients at high risk for virologic failure.     

The Impact of Choice of NNRTI on Short-Term Treatment Outcomes among HIV-Infected Patients Prescribed Tenofovir and Lamivudine in Johannesburg,South Africa

Introduction

Recent WHO guidelines for resource-limited settings recommend tenofovir in first-line antiretroviral therapy (ART) yet there are suggestions that patients receiving nevirapine with tenofovir have worse outcomes than those receiving efavirenz. We sought to compare outcomes among those taking nevirapine vs. efavirenz with tenofovir and lamivudine.

Methods

We analyzed data on ART naïve, non-pregnant patients, ≥18 years old without tuberculosis co-infection, initiating tenofovir with lamivudine and either nevirapine or efavirenz between April 1, 2010 and July 31, 2011 (when South Africa’s public-sector use of tenofovir began) at Themba Lethu Clinic in South Africa. We measured virologic suppression (viral load <400 copies/ml), virologic failure (2 consecutive viral loads >1000 copies/ml), and attrition (death/loss to follow-up) all at 12 months after ART initiation. Modified Poisson regression with robust error estimation was used to estimate risk ratios (RR) and 95% confidence intervals (CI) for predictors of each outcome.

Results

2,254 patients were prescribed efavirenz, 131 nevirapine. Patients were followed a median (range) of 12.0 (0.1–12.0) person-months. 62.2% were female and median (IQR) age was 37.7 years (31.5–44.1). Patients prescribed efavirenz had similar initiating CD4 counts (median 132 for both regimens) but were somewhat more likely to be WHO Stage III or IV (39.6% vs. 33.6%) than those prescribed nevirapine. No difference in attrition was found (aRR: 0.83; 95% CI: 0.49–1.41). Among patients with ≥1 viral load within 1 year on ART, those prescribed nevirapine were as likely to reach virologic suppression (aRR: 0.97; 95% CI: 0.88–1.07) but more likely to experience virologic failure (aRR: 1.84; 95% CI: 1.02–3.31) than those prescribed efavirenz.

Conclusions

Our results support the notion that, among patients prescribed tenofovir and lamivudine, virologic failure is more common among those taking nevirapine than among those taking efavirenz. Longer-term follow up and larger studies will be needed to confirm this finding.     

Association between NAD+ levels and anaemia among women in community‐based study

Nicotinamide adenine dinucleotide (NAD⁺) level is the protective factor of cardiovascular diseases (CVDs). In addition, anaemia is a risk factor of adverse cardiovascular outcomes in women. However, there are limited data about the association between NAD⁺ and anaemia. The aim of this study was to evaluate association of NAD⁺ with anaemia among women. A total of 727 females from Jidong community were included in the current analysis. NAD⁺ levels were tested by the cycling assay and HPLC assay using whole blood samples. Anaemia was determined by haemoglobin (Hb) concentration, and the subtypes of anaemia were further defined according to mean corpuscular volume (MCV) in blood. Multivariable logistic analysis was used to analyse the association between NAD⁺ levels and anaemia or its subtypes. The mean age of recruited subjects was 42.7 years. The proportion of anaemia by NAD⁺ levels quartiles were 19.7% (35/178), 4.8% (9/189), 3.4% (6/178) and 2.7% (5/182). Haematological parameters including haemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and red blood count (RBC) increased over NAD⁺ quartiles. Red cell volume distribution width (RDW) decreased over NAD⁺ quartiles. Compared with the lowest quartile of NAD⁺ levels (<27.6μM), the adjusted odds ratios with 95% confidence intervals of the top quartile were 0.15 (0.06–0.41) for anaemia, 0.05 (0.01–0.36) for microcytic anaemia and 0.37 (0.10–1.36) for normocytic anaemia respectively. Higher NAD⁺ levels were significantly associated with lower prevalence of anaemia among women, especially microcytic anaemia and normocytic anaemia. Haematological parameters might serve as a predictor of the blood NAD⁺ levels.     

Serum lipoprotein (a) concentrations are inversely associated with T2D,prediabetes, and insulin resistance in a middle-aged and elderly Chinese population

Lipoprotein (a) [Lp(a)], an LDL-like particle, has been proposed as a causal risk factor for CVD among general populations. Meanwhile, both serum Lp(a) and diabetes increase the risk of CVD. However, the relationship between serum Lp(a) and T2D is poorly characterized, especially in the Asian population. Therefore, we conducted a cross-sectional study in 10,122 participants aged 40 years or older in Jiading District, Shanghai, China. Our study found that the prevalence of T2D was decreased from 20.9% to 15.0% from the lowest quartile to the highest quartile of serum Lp(a) concentrations (P for trend <0.0001). Logistic regression analyses showed that the odds ratios and 95% confidence intervals of prevalent T2D for quartiles 2–4 versus quartile 1 were 0.86 (0.73–1.01), 0.88 (0.75–1.04), and 0.76 (0.64–0.90) (P for trend = 0.0002), after adjustment for traditional confounding factors. Moreover, the risks for prevalent prediabetes, insulin resistance, and hyperinsulinemia were also decreased from the lowest to the top quartile. This inverse association between serum Lp(a) and T2D was not appreciably changed after we adjusted hypoglycemic medications or excluded the subjects with hypoglycemic and/or lipid-lowering agents and/or a history of self-reported CVD.     

Comparisons of Adherence to Antiretroviral Therapy in a High- Risk Population in China: A Systematic Review and Meta-Analysis

Background

Reports on antiretroviral therapy (ART) adherence are scare in China; we performed this meta-analysis to estimate ART adherence rates in different populations at high risk for HIV transmission in China.

Methods

We searched PubMed, Chinese Biomedical Literature Database (Chinese), China National Knowledge Infrastructure (Chinese), and Wanfang (Chinese) to identify studies published from January 1985 to May 2015. We used random-effects meta-analysis to calculate weighted mean estimates across studies and 95% CIs. Data were pooled with proportions transformed prior to pooling using the Freeman–Tukey double arcsine transformation and then back transformed to the original scale. We calculated the I² (and its 95% confidence intervals) and tau² to assess between-study heterogeneity.

Results

We identified 36 eligible articles, including 6885 HIV-positive individuals, reporting ART adherence. Pooled analysis produced an estimate of 77.61% (95% CI = 71.63–83.08) of patients with HIV with adequate adherence; however, high heterogeneity was observed between studies (I² = 96.60%, 95%CI = 96.00%-97.20%; tau² = 0.16). Three studies, which included 149 old HIV-infected patients, reported the highest ART adequate adherence rate (89.39%, 95% CI = 72.01–99.26) with high heterogeneity between the studies (I² = 86.20%, 95%CI = 60.00–95.20%; tau² = 0.13). While, only two studies, which included 143 heterosexual transmission group (HTG) patients, reported the lowest ART adequate adherence rate (51.55%, 95% CI = 41.33–61.71) with low heterogeneity between the studies (I² = 31.3%, tau² = 0.007). In the multivariable meta-regression model, high-risk populations was the main factor explaining heterogeneity (variance explained 28.14%).

Conclusions

ART adherence in some high-risk populations (e.g., heterosexual transmission group) is below the recommended levels for maintaining virologic suppression. It is crucial to develop comprehensive intervention strategies to promote ART adherence in high-risk populations and effectively prevent the spread of HIV/AIDS in China.     

Depressive Symptoms,HIV Medication Adherence,and HIV Clinical Outcomes in Tanzania: A Prospective,Observational Study

Depressive symptoms have been shown to independently affect both antiretroviral therapy (ART) adherence and HIV clinical outcomes in high-income countries. We examined the prospective relationship between depressive symptoms and adherence, virologic failure, and suppressed immune function in people living with HIV/AIDS in Tanzania. Data from 403 study participants who were on stable ART and engaged in HIV clinical care were analyzed. We assessed crude and adjusted associations of depressive symptoms and ART adherence, both at baseline and at 12 months, using logistic regression. We used logistic generalized estimating equations to assess the association and 95% confidence intervals (CI) between depressive symptoms and both virologic failure and suppressed immune function. Ten percent of participants reported moderate or severe depressive symptoms at baseline and 31% of participants experienced virologic failure (>150 copies/ml) over two years. Depressive symptoms were associated with greater odds of reported medication nonadherence at both baseline (Odds Ratio [OR] per 1-unit increase  = 1.18, 95% CI [1.12, 1.24]) and 12 months (OR  = 1.08, 95% CI [1.03, 1.14]). By contrast, increases in depressive symptom score were inversely related to both virologic failure (OR = 0.93, 95% CI [0.87, 1.00]) and immune system suppression (OR = 0.88, 95% CI [0.79, 0.99]), though the association between depressive symptoms and clinical outcomes was less precise than for the association with nonadherence. Findings indicate a positive association between depressive symptoms and nonadherence, and also an inverse relationship between depressive symptoms and clinical outcomes, possibly due to informative loss to follow-up.     

Durable Suppression of HIV-1 after Virologic Monitoring-Based Antiretroviral Adherence Counseling in Rakai,Uganda

ObjectivesHIV viral load is recommended for monitoring antiretroviral treatment and identifying treatment failure. We assessed the durability of viral suppression after viral load-triggered adherence counseling among patients with HIV viremia 6 months after ART initiation.DesignObservational cohort enrolled in an antiretroviral treatment program in rural Uganda.MethodsParticipants who underwent routine viral load determination every 24 weeks and had at least 48 weeks of follow-up were included in this analysis. Patients with viral loads >400 copies/ml at 24 weeks of treatment were given additional adherence counseling, and all patients were followed to assess the duration of viral suppression and development of virologic failure.Results1,841 participants initiating antiretroviral therapy were enrolled in the Rakai Health Sciences Program between June 2005 and June 2011 and were followed with viral load monitoring every 24 weeks. 148 (8%) of patients did not achieve viral suppression at 24 weeks and were given additional adherence counseling. 85 (60%) of these patients had undetectable viral loads at 48 weeks, with a median duration of viral suppression of 240 weeks (IQR 193-288 weeks). Failure to achieve an undetectable viral load at 48 weeks was associated with age <30 years and 24 week viral load >2,000 copies/ml in multivariate logistic regression analysis.ConclusionsThe majority of patients with persistent viremia who were provided adherence counseling achieved robust viral suppression for a median 4.6 years. Access to virologic monitoring and adherence counseling is a priority in resource-limited settings.     

Association between Soluble (Pro)Renin Receptor Concentration in Cord Blood and Small for Gestational Age Birth: A Cross-Sectional Study

Objective

The (pro)renin receptor [(P)RR] has been recognized as a multifunctional receptor. The purpose of this study was to assess the association between plasma soluble (P)RR [s(P)RR] concentration in human cord blood (i.e., neonatal blood at birth) and small for gestational age (SGA) birth.

Methods

Participants were women with a singleton pregnancy who delivered at the National Center for Child Health and Development between January 2010 and December 2011. Inclusion criteria were availability of maternal pre-pregnancy and paternal body mass index, and the absence of structural anomalies in neonates. s(P)RR concentration in cord blood was measured in 621 neonates. The 621 pairs of mothers and neonates were categorized into four groups based on quartiles of s(P)RR concentrations in cord blood. SGA was defined as a birth weight below the 10^th percentile for gestational age. Logistic regression analysis was performed to assess the association between cord plasma s(P)RR concentration (quartiles) and incidence of SGA births.

Results

Among 621 neonates, 55 (8.9%) were diagnosed as SGA (SGA group) and 566 (91.1%) were not (non-SGA group). Average s(P)RR concentration in cord blood was 66.1±12.6 ng/ml (mean±standard deviation). There were 155 pairs in the first plasma s(P)RR concentration quartile (Q1: <58.2 ng/ml), 153 pairs in the second quartile (Q2: 58.2–65.1 ng/ml), 157 pairs in the third quartile (Q3: 65.1–73.1 ng/ml) and 156 pairs in the fourth quartile (Q4: >73.1 ng/ml). The distribution of SGA births was 18 (11.6%) in Q1, 14 (9.2%) in Q2, 16 (10.2%) in Q3 and 7 (4.5%) in Q4, respectively. The odds ratio of SGA births was 0.24 (95% confidence interval: 0.08–0.71) for the fourth quartile compared to the first quartile in multivariate models. The P-value for trend was also significant (P = 0.020).

Conclusion

High s(P)RR concentration is associated with a lower SGA birth likelihood.     

The Uptake of Integrated Perinatal Prevention of Mother-to-Child HIV Transmission Programs in Low- and Middle-Income Countries: A Systematic Review

Background

The objective of this review was to assess the uptake of WHO recommended integrated perinatal prevention of mother-to-child transmission (PMTCT) of HIV interventions in low- and middle-income countries.

Methods and Findings

We searched 21 databases for observational studies presenting uptake of integrated PMTCT programs in low- and middle-income countries. Forty-one studies on programs implemented between 1997 and 2006, met inclusion criteria. The proportion of women attending antenatal care who were counseled and who were tested was high; 96% (range 30–100%) and 81% (range 26–100%), respectively. However, the overall median proportion of HIV positive women provided with antiretroviral prophylaxis in antenatal care and attending labor ward was 55% (range 22–99%) and 60% (range 19–100%), respectively. The proportion of women with unknown HIV status, tested for HIV at labor ward was 70%. Overall, 79% (range 44–100%) of infants were tested for HIV and 11% (range 3–18%) of them were HIV positive. We designed two PMTCT cascades using studies with outcomes for all perinatal PMTCT interventions which showed that an estimated 22% of all HIV positive women attending antenatal care and 11% of all HIV positive women delivering at labor ward were not notified about their HIV status and did not participate in PMTCT program. Only 17% of HIV positive antenatal care attendees and their infants are known to have taken antiretroviral prophylaxis.

Conclusion

The existing evidence provides information only about the initial PMTCT programs which were based on the old WHO PMTCT guidelines. The uptake of counseling and HIV testing among pregnant women attending antenatal care was high, but their retention in PMTCT programs was low. The majority of women in the included studies did not receive ARV prophylaxis in antenatal care; nor did they attend labor ward. More studies evaluating the uptake in current PMTCT programs are urgently needed.     

Socio Economic Position in TB Prevalence and Access to Services: Results from a Population Prevalence Survey and a Facility-Based Survey in Bangladesh

Background

In Bangladesh DOTS has been provided free of charge since 1993, yet information on access to TB services by different population group is not well documented. The objective of this study was to assess and compare the socio economic position (SEP) of actively detected cases from the community and the cases being routinely detected under National Tuberculosis Control Programme (NTP) in Bangladesh.

Methods and Findings

SEP was assessed by validated asset item for each of the 21,427 households included in the national tuberculosis prevalence survey 2007–2009. A principal component analysis generated household scores and categorized in quartiles. The distribution of 33 actively identified cases was compared with the 240 NTP cases over the identical SEP quartiles to evaluate access to TB services by different groups of the population. The population prevalence of tuberculosis was 5 times higher in the lowest quartiles of population (95.4, 95% CI: 48.0–189.7) to highest quartile population (19.5, 95% CI: 6.9–55.0). Among the 33 cases detected during survey, 25 (75.8%) were from lower two quartiles, and the rest 8 (24.3%) were from upper two quartiles. Among TB cases detected passively under NTP, more than half of them 137 (57.1%) were from uppermost two quartiles, 98 (41%) from the second quartile, and 5 (2%) in the lowest quartile of the population. This distribution is not affected when adjusted for other factors or interactions among them.

Conclusions

The findings indicate that despite availability free of charge, DOTS is not equally accessed by the poorer sections of the population. However, these figures should be interpreted with caution since there is a need for additional studies that assess in-depth poverty indicators and its determinants in relation to access of the TB services provided in Bangladesh.     

Effectiveness of Patient Adherence Groups as a Model of Care for Stable Patients on Antiretroviral Therapy in Khayelitsha,Cape Town,South Africa

Background

Innovative models of care are required to cope with the ever-increasing number of patients on antiretroviral therapy in the most affected countries. This study, in Khayelitsha, South Africa, evaluates the effectiveness of a group-based model of care run predominantly by non-clinical staff in retaining patients in care and maintaining adherence.

Methods and Findings

Participation in “adherence clubs” was offered to adults who had been on ART for at least 18 months, had a current CD4 count >200 cells/ml and were virologically suppressed. Embedded in an ongoing cohort study, we compared loss to care and virologic rebound in patients receiving the intervention with patients attending routine nurse-led care from November 2007 to February 2011. We used inverse probability weighting to estimate the intention-to-treat effect of adherence club participation, adjusted for measured baseline and time-varying confounders. The principal outcome was the combination of death or loss to follow-up. The secondary outcome was virologic rebound in patients who were virologically suppressed at study entry. Of 2829 patients on ART for >18 months with a CD4 count above 200 cells/µl, 502 accepted club participation. At the end of the study, 97% of club patients remained in care compared with 85% of other patients. In adjusted analyses club participation reduced loss-to-care by 57% (hazard ratio [HR] 0.43, 95% CI = 0.21–0.91) and virologic rebound in patients who were initially suppressed by 67% (HR 0.33, 95% CI = 0.16–0.67).

Discussion

Patient adherence groups were found to be an effective model for improving retention and documented virologic suppression for stable patients in long term ART care. Out-of-clinic group-based models facilitated by non-clinical staff are a promising approach to assist in the long-term management of people on ART in high burden low or middle-income settings.     

Effectiveness of Multidrug Antiretroviral Regimens to Prevent Mother-to-Child Transmission of HIV-1 in Routine Public Health Services in Cameroon

Background

Multidrug antiretroviral (ARV) regimens including HAART and short-course dual antiretroviral (sc-dARV) regimens were introduced in 2004 to improve Prevention of Mother-to-Child Transmission (PMTCT) in Cameroon. We assessed the effectiveness of these regimens from 6–10 weeks and 12 months of age, respectively.

Methodology/Findings

We conducted a retrospective cohort study covering the period from October 2004 to March 2008 in a reference hospital in Cameroon. HIV-positive pregnant women with CD4 ≤350 cells/mm³ received first-line HAART [regimen 1] while the others received ARV prophylaxis including sc-dARV or single dose nevirapine (sd-NVP). Sc-dARV included at least two drugs according to different gestational ages: zidovudine (ZDV) from 28–32 weeks plus sd-NVP [regimen 2], ZDV and lamuvidine (3TC) from 33–36 weeks plus sd-NVP [regimen 3]. When gestational age was ≥37 weeks, women received sd-NVP during labour [regimen 4]. Infants received sd-NVP plus ZDV and 3TC for 7 days or 30 days. Early diagnosis (6–10 weeks) was done, using b-DNA and subsequently RT-PCR. We determined early MTCT rate and associated risk factors using logistic regression. The 12-month HIV-free survival was assessed using Cox regression. Among 418 mothers, 335 (80%) received multidrug ARV regimens (1, 2, and 3) and MTCT rate with multidrug regimens was 6.6% [95%CI: 4.3–9.6] at 6 weeks, without any significant difference between regimens. Duration of mother''s ARV regimen <4 weeks [OR = 4.7, 95%CI: 1.3–17.6], mother''s CD4 <350 cells/mm³ [OR = 6.4, 95%CI: 1.8–22.5] and low birth weight [OR = 4.0, 95%CI: 1.4–11.3] were associated with early MTCT. By 12 months, mixed feeding [HR = 8.7, 95%CI: 3.6–20.6], prematurity [HR = 2.3, 95%CI: 1.2–4.3] and low birth weight were associated with children''s risk of progressing to infection or death.

Conclusions

Multidrug ARV regimens for PMTCT are feasible and effective in routine reference hospital. Early initiation of ARV during pregnancy and proper obstetrical care are essential to improve PMTCT.     

Red Cell Distribution Width in Relation to Incidence of Stroke and Carotid Atherosclerosis: A Population-Based Cohort Study

BackgroundIncreased red cell distribution width (RDW) has been related to poor prognosis in patients with cardiovascular disease, and is a predictor of cardiovascular mortality in the general population. The purpose of the present study was to investigate if RDW is associated with increased incidence of stroke and its subtypes in individuals from the general population.MethodsRed cell distribution width was measured in 26,879 participants (16,561 women and 10,318 men aged 45–73 years) without history of coronary events or stroke, from the population-based Malmö Diet and Cancer Study. Incidences of total stroke and stroke subtypes over a mean follow-up of 15.2 years were calculated in relation to sex-specific quartiles of RDW. The presence of carotid plaque and intima–media thickness, as assessed by ultrasound, was studied in relation to RDW in a randomly selected subcohort (n = 5,309).ResultsIncidences of total stroke (n = 1,869) and cerebral infarction (n = 1,544) were both increased in individuals with high RDW. Hazard ratios (HRs) in the highest compared to the lowest quartile were 1.31 for total stroke (95% confidence interval [CI]: 1.11–1.54, p for trend = 0.004) and 1.32 for cerebral infarction (95% CI: 1.10–1.58, p for trend = 0.004) after adjustment for stroke risk factors and hematological parameters. The adjusted HR for intracerebral hemorrhage (n = 230) was 1.44 (95% CI: 0.90–2.30) and the HR for subarachnoid hemorrhage (n = 75) was 0.94 (95% CI: 0.43–2.07), in the highest compared to the lowest quartile of RDW. Red cell distribution width was positively associated with intima–media thickness of the common carotid artery (p for trend = 0.011).ConclusionsRed cell distribution width in the highest quartile was associated with increased incidence of total stroke and cerebral infarction. There was no significant association between RDW and incidence of intracerebral or subarachnoid hemorrhage.     

Outcomes in a Cohort of Patients Started on Antiretroviral Treatment and Followed up for a Decade in an Urban Clinic in Uganda

Background

Short-medium term studies from sub-Saharan Africa show that, despite high early mortality, substantial loss to program, and high rates toxicity, patients on antiretroviral treatment have achieved outcomes comparable to those in developed settings. However, these studies were unable to account for long term outcomes of patients as they stayed longer on treatment.

Objectives

We aim to describe ten years outcomes of one of the first cohort of HIV positive patients started on antiretroviral treatment (ART) in Sub-Saharan Africa.

Methods

We report 10-years outcomes including mortality, retention, CD4-count response, virological outcomes, ART regimens change from a prospective cohort of 559 patients initiating ART and followed up for 10 years Uganda.

Results

Of 559 patients, 69.1% were female, median age (IQR) was 38 (33–44) years, median CD4-count (IQR) 98 (21–163) cell/μL; 74% were started on stavudine, lamivudine and nevirapine, 26% on zidovudine, lamivudine and efavirenz. After 10 years 361 (65%) patients were still in the study; 127 (22.7%) had died; 30 (5%) were lost to follow-up; 27 (5%) transferred; 18 (3%) withdrew consent. The probability of death was high in the first year (0.15, 95%, CI 0.12–0.18). The median CD4 count increased from 98 to 589 cell/μL (IQR: 450–739 cell/μL) with a median increase of 357 cells/μL (IQR: 128–600 cells/μL); 7.4% never attained initial viral suppression and of those who did 31.7% experienced viral failure. Three hundred and two patients had at least one drug substitution while on first line after a median of 40 months; 66 (11.9%) of the patients were switched to a second line PI-based regimen due to confirmed treatment failure.

Conclusions

Despite the high rate of early mortality due to advanced disease at presentation the outcomes from this cohort are encouraging, particularly the remarkable and incremental immune-recovery and a satisfactory rate of virologic suppression.     

Nevirapine- Versus Lopinavir/Ritonavir-Based Initial Therapy for HIV-1 Infection among Women in Africa: A Randomized Trial

Background

Nevirapine (NVP) is widely used in antiretroviral treatment (ART) of HIV-1 globally. The primary objective of the AA5208/OCTANE trial was to compare the efficacy of NVP-based versus lopinavir/ritonavir (LPV/r)-based initial ART.

Methods and Findings

In seven African countries (Botswana, Kenya, Malawi, South Africa, Uganda, Zambia, and Zimbabwe), 500 antiretroviral-naïve HIV-infected women with CD4<200 cells/mm³ were enrolled into a two-arm randomized trial to initiate open-label ART with tenofovir (TDF)/emtricitabine (FTC) once/day plus either NVP (n = 249) or LPV/r (n = 251) twice/day, and followed for ≥48 weeks. The primary endpoint was time from randomization to death or confirmed virologic failure ([VF]) (plasma HIV RNA<1 log₁₀ below baseline 12 weeks after treatment initiation, or ≥400 copies/ml at or after 24 weeks), with comparison between treatments based on hazard ratios (HRs) in intention-to-treat analysis. Equivalence of randomized treatments was defined as finding the 95% CI for HR for virological failure or death in the range 0.5 to 2.0. Baseline characteristics were (median): age = 34 years, CD4 = 121 cells/mm³, HIV RNA = 5.2 log₁₀copies/ml. Median follow-up = 118 weeks; 29 (6%) women were lost to follow-up. 42 women (37 VFs, five deaths; 17%) in the NVP and 50 (43 VFs, seven deaths; 20%) in the LPV/r arm reached the primary endpoint (HR 0.85, 95% CI 0.56–1.29). During initial assigned treatment, 14% and 16% of women receiving NVP and LPV/r experienced grade 3/4 signs/symptoms and 26% and 22% experienced grade 3/4 laboratory abnormalities. However, 35 (14%) women discontinued NVP because of adverse events, most in the first 8 weeks, versus none for LPV/r (p<0.001). VF, death, or permanent treatment discontinuation occurred in 80 (32%) of NVP and 54 (22%) of LPV/r arms (HR = 1.7, 95% CI 1.2–2.4), with the difference primarily due to more treatment discontinuation in the NVP arm. 13 (45%) of 29 women tested in the NVP versus six (15%) of 40 in the LPV/r arm had any drug resistance mutation at time of VF.

Conclusions

Initial ART with NVP+TDF/FTC demonstrated equivalent virologic efficacy but higher rates of treatment discontinuation and new drug resistance compared with LPV/r+TDF/FTC in antiretroviral-naïve women with CD4<200 cells/mm³.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00089505","term_id":"NCT00089505"}}NCT00089505 Please see later in the article for the Editors'' Summary