Prevalence and characteristics of metabolic syndrome and its components among adults living with and without HIV in Nigeria: a single-center study.

BACKGROUND: Persons living with HIV (PLHIV) now live longer due to effective combination antiretroviral therapy. However, emerging evidence indicates that they may be at increased risk for some cardiometabolic disorders. We compared the prevalence of metabolic syndrome (MetS) and its component disorders between persons living with and without HIV in Nigeria. METHODS: This was a cross-sectional analysis of baseline data from a prospective cohort study of non-communicable diseases among PLHIV along with age- and sex-matched persons without HIV (PWoH) at the University of Abuja Teaching Hospital Nigeria. We collected sociodemographic and clinical data, including anthropometric measures and results of relevant laboratory tests. MetS was defined using a modification of the third report of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) criteria. RESULTS: Of the 440 PLHIV and 232 PWoH, women constituted 50.5% and 51.3% respectively. The median age of the PLHIV was 45 years while that of the PWoH was 40 years. The prevalence of MetS was 30.7% (95% CI: 26.4%, 35.2%) and 22.8% (95% CI: 17.6%, 28.8%) among the PLHIV and PWoH respectively (P = 0.026). Independent associations were found for older age (P < 0.001), female sex (P < 0.001), family history of diabetes (P < 0.001), family history of hypertension (P = 0.013) and alcohol use (P = 0.015). The prevalence of component disorders for PLHIV versus PWoH were as follows: high blood pressure (22.3% vs 20.3%), prediabetes (33.8% vs 21.1%), diabetes (20.5% vs 8.2%), high triglycerides (24.5% vs 17.2%), low HDL-Cholesterol (51.1% vs 41.4%), and abdominal obesity (38.4% vs 37.1%). Adjusting for age and sex, prediabetes, diabetes, and low HDL-Cholesterol were significantly associated with HIV status. Duration on antiretroviral therapy, protease inhibitor-based regimen, CD4 count, and viral load were associated with some of the disorders mostly in unadjusted analyses. CONCLUSION: We found a high burden of MetS and its component disorders, with significantly higher prevalence of dysglycemia and dyslipidemia among PLHIV as compared to PWoH. Integration of strategies for the prevention and management of MetS disorders is needed in HIV treatment settings.

Predictors of first-line antiretroviral therapy failure among adults and adolescents living with HIV/AIDS in a large prevention and treatment program in Nigeria.

BACKGROUND: A substantial number of persons living with HIV (PLWH) in Nigeria do not experience durable viral suppression on first-line antiretroviral therapy (ART). Understanding risk factors for first-line treatment failure informs patient monitoring practices and distribution of limited resources for second-line regimens. We determined predictors of immunologic and virologic failures in a large ART delivery program in Abuja, Nigeria. METHODS: A retrospective cohort study was conducted at the University of Abuja Teaching Hospital, a tertiary health care facility, using data from February 2005 to December 2014 in Abuja, Nigeria. All PLWH aged ≥ 15 years who initiated ART with at least 6-month follow-up and one CD4 measurement were included. Immunologic failure was defined as a CD4 decrease to or below pre-ART level or persistent CD4 < 100 cells per mm3 after 6 months on ART. Virologic failure (VF) was defined as two consecutive HIV-1 RNA levels > 1000 copies/mL after at least 6 months of ART and enhanced adherence counselling. HIV drug resistance (Sanger sequences) was analyzed using the Stanford HIV database algorithm and scored for resistance to common nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Univariate and multivariate log binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Of 12,452 patients followed, a total of 5928 initiated ART with at least 6 months of follow-up and one CD4 measurement. The entry point for 3924 (66.2%) was through the program's own voluntary counseling and testing (VCT) center, while 1310 (22.1%) were referred from an outside clinic/program, 332 (5.6%) in-patients, and 373 (6.3%) through other entry points including prevention of mother to child transmission (PMTCT) and transferred from other programs. The mean CD4 at enrollment in care was 268 ± 23.7 cells per mm3, and the mean HIV-1 RNA was 3.3 ± 1.3.log10 copies/mL. A total of 3468 (80.5%) received nevirapine (NVP) and 2260 (19.5%) received efavirenz (EFV)-based regimens. A total of 2140 (36.1%) received tenofovir (TDF); 2662 (44.9%) zidovudine (AZT); and 1126 (19.0%) stavudine (d4T). Among those receiving TDF, 45.0% also received emtricitabine (FTC). In a multivariate model, immunologic failure was more common among PLWH with female gender as compared to male [RR (95% CI) 1.22 (1.07-1.40)] and less common among those who entered care at the program's VCT center as compared to other entry points [0.79 (0.64-0.91)], WHO stage 3/4 as compared to 1/2 [0.19 (0.16-0.22)], or CD4 200 + cells per mm3 as compared to lower [0.19 (0.16-0.22)]. Virologic failure was more common among PLWH who entered care at the program's VCT center as compared to other entry points [RR (95% CI) 1.45 (1.11-1.91) and those with CD4 < 200 cells per mm3 at entry into care as compared to higher [1.71 (1.36-2.16)]. Of 198 patient-derived samples sequenced during virologic failure, 42 (21%) were wild-type; 145 (73%) carried NNRTI drug resistance mutations; 151 (76.3%) M184I/V; 29 (14.6%) had ≥ 3 TAMs, and 37 (18.7%) had K65R, of whom all were on TDF-containing first-line regimens. CONCLUSIONS: In this cohort of Nigerian PLWH followed for a period of 9 years, immunologic criteria poorly predicted virologic failure. Furthermore, a subset of samples showed that patients failing ART for extended periods of time had HIV-1 strains harboring drug resistance mutations.

Correlates and determinants of Early Infant Diagnosis outcomes in North-Central Nigeria.

BACKGROUND: A negative status following confirmatory Early Infant Diagnosis (EID) is the desired pediatric outcome of prevention of Mother to Child Transmission (PMTCT) programs. EID impacts epidemic control by confirming non-infected HIV-exposed infants (HEIs) and prompting timely initiation of ART in HIV-infected babies which improves treatment outcomes. OBJECTIVES: We explored factors associated with EID outcomes among HEI in North-Central Nigeria. METHOD: This is a cross-sectional study using EID data of PMTCT-enrollees matched with results of HEI's dried blood samples (DBS), processed for DNA-PCR from January 2015 through July 2017. Statistical analyses were done using SPSS version 20.0 to generate frequencies and examine associations, including binomial logistic regression with p < 0.05 being statistically significant. RESULTS: Of 14,448 HEI in this analysis, 51.8% were female and 95% (n = 12,801) were breastfed. The median age of the infants at sample collection was 8 weeks (IQR 6-20), compared to HEI tested after 20 weeks of age, those tested earlier had significantly greater odds of a negative HIV result (≤ 6 weeks: OR = 3.8; 6-8 weeks: OR = 2.1; 8-20 weeks: OR = 1.5) with evidence of a significant linear trend (p < 0.001). Similarly, HEI whose mothers received combination antiretroviral therapy (cART) before (OR = 11.8) or during the index pregnancy (OR = 8.4) had significantly higher odds as compared to those whose mothers did not receive cART. In addition, HEI not breastfed had greater odds of negative HIV result as compared to those breastfed (OR = 1.9). CONCLUSIONS: cART prior to and during pregnancy, earlier age of HEI at EID testing and alternative feeding other than breastfeeding were associated with an increased likelihood of being HIV-negative on EID. Therefore, strategies to scale-up PMTCT services are needed to mitigate the burden of HIV among children.

Performance and trend for quality of service in a large HIV/AIDS treatment program in Nigeria.

BACKGROUND: As antiretroviral therapy (ART) programs expand access, there is an increase in burden to a healthcare system. These results are reduced provider-patient contact time and poor programmatic and patient outcomes. Quality management offers providers a standardized approach for addressing the appropriateness of care to be applied in resource-limited settings. This study aimed to determine the trend of performance on HIV/AIDS quality management indicators of health facilities providing ART over a period of 5 years. METHODS: The annual performance scores of quality of care (QoC) indicators of 31 health facilities providing ART was extracted from a database covering a period of 5 years (from October 2008 to September 2012). The data are percentages that indicate scores of each health facility assessed based on compliance to National ART guidelines categorized into several indicator domains. A Chi square statistic for the trend, as well as test for departure from the trend line was determined. The p value associated with each indicator provides the significant level for testing an alternative hypothesis that the rate of change over the period considered for that indicator does not equal to zero. The slope of the regression line also gives the magnitude of the rate of change for each indicator by healthcare level across the review period. RESULTS: Generally, performance trends showed improvement across most indicator domains. The highest improvement occurred for "3 month loss to follow-up" and "1 year no-visit", with scores declining from 37 to 3%, and 42% to 12% respectively. However, there was a sharp decline in performance between 2010 and 2012 in weight monitoring of patients (p < 0.01), adherence assessment to ARVs (p < 0.01) and hematocrit measurements (p = 0.01). The aggregate rate of change ß, as obtained from the slope of the trend line is highly significant (p < 0.01) for all the quality of care indicators considered, whether improving or declining. CONCLUSION: Periodic assessment to determine HIV/AIDS quality of care can guide rapid scale-up of services to achieve universal coverage in resource-limited settings. Determining trends to understand patterns is very useful for improving programmatic and patient outcomes.

Cognitive Function Among Antiretroviral Treatment-Naive Individuals Infected With Human Immunodeficiency Virus Type 1 Subtype G Versus CRF02_AG in Nigeria.

Background: Human immunodeficiency virus type 1 (HIV-1) subtype has been shown to be associated with disease progression. We compared cognitive function between individuals infected with HIV-1 subtype G and CRF02_AG in Nigeria. Methods: For this cross-sectional study, samples were analyzed from 146 antiretroviral-naive participants. Genotypic analysis of plasma HIV RNA was performed by nested polymerase chain reaction of protease and reverse transcriptase genes, and sequences were aligned with curated HIV-1 subtype references. Cognitive status was determined using demographically adjusted T scores and global deficit score (GDS) obtained from a comprehensive neuropsychological test battery. Results: A total of 76 (52.1%) participants were infected with CRF02_AG, 48 (32.8%) with subtype G, and 22 (15.1%) with other HIV-1 strains. In a multivariable linear regression adjusting for plasma HIV RNA, CD4 count, and depression score, mean global T score was lower among subtype G-infected compared with CRF02_AG-infected participants (mean difference, -3.0 [95% confidence interval {CI}, -5.2, to -.7]; P = .011). Also, T scores were significantly lower among subtype G- than CRF02_AG-infected participants for the speed of information processing, executive function, and verbal fluency ability domains. Adjusting for similar variables in a logistic regression, the odds of global cognitive impairment (GDS ≥0.5) were 2.2 times higher among subtype G compared with CRF02_AG-infected participants (odds ratio, 2.2 [95% CI, .9-5.4]; P = .078). Conclusions: Cognitive performance was significantly worse among antiretroviral-naive individuals with HIV-1 subtype G vs CRF02_AG infection. Further studies are required to characterize the mechanistic basis for these differences.

Plasma HIV RNA level is associated with neurocognitive function among HIV-1-infected patients in Nigeria.

Plasma HIV RNA level has been shown to correlate with HIV disease progression, morbidity, and mortality. We examined the association between levels of plasma HIV RNA and cognitive function among patients in Nigeria. A total of 179 HIV-1-infected participants with available plasma HIV RNA results and followed longitudinally for up to 2 years were included in this study. Blood samples from participants were used for the measurement of plasma HIV RNA and CD4+ T cell count. Utilizing demographic and practice effect-adjusted T scores obtained from a seven-domain neuropsychological test battery, cognitive status was determined by the global deficit score (GDS) approach, with a GDS ≥ 0.5 indicating cognitive impairment. In a longitudinal multivariable linear regression analysis, adjusting for CD4 cell count, Beck's Depression Score, age, gender, years of education, and antiretroviral treatment status, global T scores decreased by 0.35 per log10 increase in plasma HIV RNA [p = 0.033]. Adjusting for the same variables in a multivariable logistic regression, the odds of neurocognitive impairment were 28% higher per log10 increase in plasma HIV RNA (OR 1.28 [95% CI 1.08, 1.51]; p = 0.005). There were statistically significant associations for the speed of information processing, executive, and verbal fluency domains in both linear and logistic regression analyses. We found a significant association between plasma HIV RNA levels and cognitive function in both baseline (cross-sectional) and longitudinal analyses. However, the latter was significantly attenuated due to weak association among antiretroviral-treated individuals.

Peripheral blood lymphocyte HIV DNA levels correlate with HIV associated neurocognitive disorders in Nigeria.

Mononuclear cells play key roles in the pathogenic mechanisms leading to HIV-associated neurocognitive disorders (HANDs). We examined the association between HIV DNA within peripheral blood mononuclear cell (PBMC) subsets and HAND in Nigeria. PBMCs were collected at baseline from 36 antiretroviral naive participants. CD14+ cells and T&B lymphocyte fractions were isolated by, respectively, positive and negative magnetic bead separation. Total HIV DNA within CD14+ and T&B cells were separately quantified using real-time PCR assay targeting HIV LTR-gag and cell input numbers determined by CCR5 copies/sample. Utilizing demographically adjusted T scores obtained from a 7-domain neuropsychological test battery, cognitive status was determined by the global deficit score (GDS) approach, with a GDS of ≥0.5 indicating cognitive impairment. In a linear regression adjusting for plasma HIV RNA, CD4 and lymphocyte count, Beck's depression score, and years of education, there was 0.04 lower log10 HIV DNA copies within T&B lymphocytes per unit increase in global T score (p = 0.02). Adjusting for the same variables in a logistic regression, the odds of cognitive impairment were 6.2 times greater per log10 increase in HIV DNA within T&B lymphocytes (p = 0.048). The association between cognitive impairment and HIV DNA within CD14+ monocytes did not reach statistical significance. In this pretreatment cohort with mild cognitive dysfunction, we found a strong association between levels of HIV DNA within the lymphocyte subset and HAND independent of plasma HIV RNA. These findings likely reflect the neurologic impact of a larger HIV reservoir and active viral replication.

Proceedings from the NIMH symposium on "NeuroAIDS in Africa: neurological and neuropsychiatric complications of HIV".

Despite major advances in HIV-1 treatment, the prevalence of HIV-associated neurocognitive disorders (HAND) remains a problem, particularly as individuals on suppressive treatment continue to live longer. To facilitate discussion on emerging and future directions in HAND research, a meeting was held in Durban, South Africa in March 2015 as part of the Society of Neuroscientists of Africa (SONA) conference. The objective of the meeting was to assess the impact of HIV subtype diversity on HAND and immunological dysfunction. The meeting brought together international leaders in the area of neurological complications of HIV-1 infection with special focus on the African population. Research presentations indicated that HAND was highly prevalent and that inflammatory cytokines and immune-activation played important roles in progression of neurocognitive impairment. Furthermore, children on antiretroviral therapy were also at risk for developing neurocognitive impairment. With respect to the effect of HIV-1 subtype diversity, analyses of HIV-1 clade C infection among South Africans revealed that clade C infection induced cognitive impairment that was independent of the substitution in HIV-1 Trans-Activator of Transcription (Tat; C31S). At the cellular level, a Zambian study showed that clade C infection resulted in reduced brain cell death compared with clade B infection suggesting clade specific variations in mediating brain cell injury. Furthermore, ex vivo Tat protein from clade CRF02_AG, prevalent in West/ Central Africa, exhibited reduced disruption of brain endothelium compared with clade B Tat protein. Discussions shed light on future research directions aimed at understanding biomarkers and disease mechanisms critical for HAND.

Chloroquine-azithromycin combination antimalarial treatment decreases risk of respiratory- and gastrointestinal-tract infections in Malawian children.

BACKGROUND: Chloroquine-azithromycin is being evaluated as combination therapy for malaria. It may provide added benefit in treating or preventing bacterial infections that occur in children with malaria. OBJECTIVE: We aim to evaluate the effect of treating clinical malaria with chloroquine-azithromycin on the incidence of respiratory-tract and gastrointestinal-tract infections compared to treatment with chloroquine monotherapy. METHODS: We compared the incidence density and time to first events of respiratory-tract and gastrointestinal-tract infections among children assigned to receive chloroquine-azithromycin or chloroquine for all symptomatic malaria episodes over the course of 1 year in a randomized longitudinal trial in Blantyre, Malawi. RESULTS: The incidence density ratios of total respiratory-tract infections and gastrointestinal-tract infections comparing chloroquine-azithromycin to chloroquine monotherapy were 0.67 (95% confidence interval [CI], .48, .94) and 0.74 (95% CI, .55, .99), respectively. The time to first lower-respiratory-tract and gastrointestinal-tract infections were significantly longer in the chloroquine-azithromycin arm compared to the chloroquine arm (P = .04 and P = .02, respectively). CONCLUSIONS: Children treated routinely with chloroquine-azithromycin had fewer respiratory and gastrointestinal-tract infections than those treated with chloroquine alone. This antimalarial combination has the potential to reduce the burden of bacterial infections among children in malaria-endemic countries.

Dynamics of the infant gut microbiota in the first 18 months of life: the impact of maternal HIV infection and breastfeeding.

BACKGROUND: Access to antiretroviral therapy (ART) during pregnancy and breastfeeding for mothers with HIV has resulted in fewer children acquiring HIV peri- and postnatally, resulting in an increase in the number of children who are exposed to the virus but are not infected (HEU). HEU infants have an increased likelihood of childhood infections and adverse growth outcomes, as well as increased mortality compared to their HIV-unexposed (HUU) peers. We explored potential differences in the gut microbiota in a cohort of 272 Nigerian infants born to HIV-positive and negative mothers in this study during the first 18 months of life. RESULTS: The taxonomic composition of the maternal vaginal and gut microbiota showed no significant differences based on HIV status, and the composition of the infant gut microbiota at birth was similar between HUU and HEU. Longitudinal taxonomic composition of the infant gut microbiota and weight-for-age z-scores (WAZ) differed depending on access to breast milk. HEU infants displayed overall lower WAZ than HUU infants at all time points. We observed a significantly lower relative abundance of Bifidobacterium in HEU infants at 6 months postpartum. Breast milk composition also differed by time point and HIV infection status. The antiretroviral therapy drugs, lamivudine and nevirapine, as well as kynurenine, were significantly more abundant in the breast milk of mothers with HIV. Levels of tiglyl carnitine (C5) were significantly lower in the breast milk of mothers without HIV. ART drugs in the breast milk of mothers with HIV were associated with a lower relative abundance of Bifidobacterium longum. CONCLUSIONS: Maternal HIV infection was associated with adverse growth outcomes of HEU infants in this study, and these differences persist from birth through at least 18 months, which is a critical window for the development of the immune and central nervous systems. We observed that the relative abundance of Bifidobacterium spp. was significantly lower in the gut microbiota of all HEU infants over the first 6 months postpartum, even if HEU infants were receiving breast milk. Breastfeeding was of benefit in our HEU infant cohort in the first weeks postpartum; however, ART drug metabolites in breast milk were associated with a lower abundance of Bifidobacterium. Video abstract.

Outcomes of HIV Positive Children and Adolescents Initiated on Antiretroviral Treatment in Nigeria (2007-2016).

Background: This manuscript aimed to examine treatment outcomes of HIV-positive children and adolescents. Methods: We retrospectively analyzed data of a sample of patients aged 0-19 years who initiated ART (October 2007-September 2016) in participating sites in 30 states and the Federal Capital Territory in Nigeria. Results: Among 4006 patients alive at the end of the follow up period, 138 (3.4%) were LTFU. Adolescents had a significantly higher risk of being LTFU than children aged 3-5 years (HR 2.47 [95% CI 1.40-4.34]). Patients with advanced disease had a significantly higher risk of being LTFU (Stage IV HR, 3.66 [95% CI: 2.00-6.68]). On average, optimal ART refill adherence was met by 67.3% of patients. Conclusion: Our findings suggest that focusing on preventing and managing advanced disease and interventions supporting adolescents when transferring to adult care is warranted.

Asymptomatic Malaria Co-infection of HIV-Infected Adults in Nigeria: Prevalence of and Impact on Cognition, Mood, and Biomarkers of Systemic Inflammation.

BACKGROUND: HIV and malaria are associated with immunological perturbations and neurocognitive disorders even when asymptomatic. However, the effect of asymptomatic malaria (AM) in HIV-infected adults on neurocognitive impairment (NCI) is not well understood. This study investigated the biomarkers of systemic inflammation and neurocognition in dually infected Nigerian adults. METHODS: We assessed the HIV and AM status of 269 adults and measured their global and domain-specific neurocognition and depression using standardized measures. Blood levels of sCD14 and sCD163 were also measured. RESULTS: The mean age of the participants (n = 269) was 33 years, 62% were women, and AM among HIV+ and HIV- was similar (36% versus 37%). NCI was found in 23% (62/269) of participants. HIV+/AM+ had a higher prevalence of impaired learning and executive functions and were more depressed than HIV-/AM- or HIV+/AM-. HIV+ with CD4 T-cell counts ≤200/µL were more impaired in the learning domain than those with >200/µL. HIV+/AM+ group had higher levels of sCD14 compared to the other 3 groups and higher levels of sCD163 than the HIV-/AM- group. Higher levels of sCD14 and sCD163 were each associated with NCI. The sCD163 (log10) levels were higher for those with 1+ versus 2+ parasitemia level. CONCLUSIONS: HIV and AM coinfection was associated with an increased risk of reduced learning and executive functions, and elevated systemic inflammation. Mood was more depressed in HIV patients with than those without AM. The mechanisms and long-term effects on neurocognition and depression among HIV+/AM+ individuals should be studied because this coinfection is common globally.

Elevated Plasma Levels of sCD14 and MCP-1 Are Associated With HIV Associated Neurocognitive Disorders Among Antiretroviral-Naive Individuals in Nigeria.

BACKGROUND: Mononuclear cells play key roles in the pathogenesis of HIV-associated neurocognitive disorders (HAND). Limited studies have looked at the association of markers of monocyte activation with HAND in Africa. We examined this association among HIV-1-infected patients in Nigeria. METHOD: A total of 190 HIV-infected treatment-naive participants with immune marker data were included in this cross-sectional study. Plasma levels of soluble CD14 (sCD14), soluble CD163, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and neopterin were measured. Demographically adjusted T scores obtained from a 7-domain neuropsychological test battery were generated, and functional status was assessed using activities of daily living questionnaire. Participants were classified as unimpaired, having asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD) in line with the "Frascati" criteria. RESULTS: Thirty-two participants (16.8%) had ANI, 14 (7.4%) had MND, whereas none had HAD. In multivariable linear regression analyses, after adjusting for age, gender, education, CD4 count, and viral load, mean levels of sCD14 were higher among those with ANI and MND as compared with the unimpaired (P = 0.033 and 0.023, respectively). Similarly, the mean level of MCP-1 was greater among those with HAND as compared with the unimpaired (P = 0.047). There were also trends for higher levels of sCD163 and TNF-α among females with MND in univariable analyses. CONCLUSIONS: Levels of monocyte activation markers correlate with the severity of impairment among individuals with HAND. The mechanisms that underlie these effects and the potential role of gender require further study.

Compromised Growth Among HIV-exposed Uninfected Compared With Unexposed Children in Nigeria.

BACKGROUND: HIV-exposed but uninfected (HEU) children may be at an increased risk of impaired growth when compared with their HIV-unexposed and uninfected (HUU) counterparts. We compared the growth patterns of HEU to HUU children in Nigeria. METHODS: Pregnant women with and without HIV infection were enrolled at the Plateau State Specialist Hospital, Jos, Nigeria. Infants born to these mothers were recruited at birth and the mother-infant pairs followed up for 18 months. Weight, length and head circumference of the infants were measured at each visit. Age- and sex-standardized Z scores were generated for each anthropometric measure using the World Health Organization Child Growth Standards. Children with length-for-age, weight-for-age and weight-for-length Z scores <-2 were classified as stunted, underweight and wasted, respectively. RESULTS: Of 415 children (307 HEU and 108 HUU) recruited for this study, 117 (28.4%), 9 (2.2%) and 32 (7.8%) infants were stunted, underweight and wasted, respectively, at birth. In a multivariable longitudinal analysis, the odds of stunting were higher among HEU as compared with HUU children [adjusted odds ratio: 2.4 (95% confidence interval: 1.4-4.1)]. Similarly, odds of being underweight were higher among the HEU children [adjusted odds ratio: 1.6 (95% confidence interval: 1.1-2.2)]. CONCLUSIONS: Linear and ponderal growth were more impaired among HEU as compared with HUU children in Nigeria during the first 18 months of life. Further studies are needed to explore the causal basis for these differences.

Brief Report: Body Mass Index and Cognitive Function Among HIV-1-Infected Individuals in China, India, and Nigeria.

BACKGROUND: Risk of cognitive impairment is increased among persons with high or low body mass index in HIV- and HIV+ populations in resource-rich settings. We examined this association among HIV+ patients in 3 resource-limited settings. METHODS: This secondary analysis included data of 761 HIV+ volunteers pooled from 3 prospective cohort studies conducted in China (n = 404; 53%), India (n = 200; 26%), and Nigeria (n = 157; 21%). World Health Organization (WHO) weight classifications were based on body mass index. T scores, adjusted for demographics and practice effects, were derived from a 7-domain neuropsychological battery. Neurocognitive impairment (NCI) was defined as global deficit score of ≥0.5. RESULTS: Overall, prevalence of NCI at baseline was 27.7% (similar across all cohorts). The overweight/obese and underweight constituted 37.3% and 15.5% of the total participants, respectively. In a multivariable logistic regression of pooled longitudinal data, adjusting for clinical and demographic variables, the odds of global NCI were 38% higher among the overweight/obese as compared to normal weight participants [odds ratio: 1.38 (95% confidence interval: 1.1 to 1.72); P = 0.005]. Similarly, the odds of global NCI were 39% higher among the underweight as compared to normal weight participants [odds ratio: 1.39 (95% confidence interval: 1.03 to 1.87); P = 0.029]. CONCLUSIONS: NCI among HIV-1-infected patients was more prevalent in both overweight/obese and underweight than normal weight individuals in 3 resource-limited settings, confirming observations in resource-rich settings. Mechanisms underlying these associations are unclear but likely differ for underweight and overweight persons.

Publisher Correction: Antiretroviral Drugs Alter the Content of Extracellular Vesicles from HIV-1-Infected Cells.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Antiretroviral Drugs Alter the Content of Extracellular Vesicles from HIV-1-Infected Cells.

To date, the most effective treatment of HIV-1 is a combination antiretroviral therapy (cART), which reduces viral replication and reverses pathology. We investigated the effect of cART (RT and protease inhibitors) on the content of extracellular vesicles (EVs) released from HIV-1-infected cells. We have previously shown that EVs contain non-coding HIV-1 RNA, which can elicit responses in recipient cells. In this manuscript, we show that TAR RNA levels demonstrate little change with the addition of cART treatment in cell lines, primary macrophages, and patient biofluids. We determined possible mechanisms involved in the selective packaging of HIV-1 RNA into EVs, specifically an increase in EV-associated hnRNP A2/B1. More recent experiments have shown that several other FDA-approved drugs have the ability to alter the content of exosomes released from HIV-1-infected cells. These findings on cART-altered EV content can also be applied to general viral inhibitors (interferons) which are used to treat other chronic infections. Additionally, we describe unique mechanisms of ESCRT pathway manipulation by antivirals, specifically the targeting of VPS4. Collectively, these data imply that, despite antiretroviral therapy, EVs containing viral products are continually released and may cause neurocognitive and immunological dysfunction.

Associations between Cognition, Gender and Monocyte Activation among HIV Infected Individuals in Nigeria.

The potential role of gender in the occurrence of HIV-related neurocognitive impairment (NCI) and associations with markers of HIV-related immune activity has not been previously examined. In this study 149 antiretroviral-naïve seropositive subjects in Nigeria (SP, 92 women and 57 men) and 58 seronegative (SN, 38 women and 20 men) were administered neuropsychological testing that assessed 7 ability domains. From the neuropsychological test scores was calculated a global deficit score (GDS), a measure of overall NCI. Percentages of circulating monocytes and plasma HIV RNA, soluble CD163 and soluble CD14 levels were also assessed. HIV SP women were found to be younger, more educated and had higher CD4+ T cell counts and borderline higher viral load measures than SP men. On the neuropsychological testing, SP women were more impaired in speed of information processing and verbal fluency and had a higher mean GDS than SN women. Compared to SP men, SP women were also more impaired in speed of information processing and verbal fluency as well as on tests of learning and memory. Numbers of circulating monocytes and plasma sCD14 and sCD163 levels were significantly higher for all SP versus all SN individuals and were also higher for SP women and for SP men versus their SN counterparts. Among SP women, soluble CD14 levels were slightly higher than for SP men, and SP women had higher viral load measurements and were more likely to have detectable virus than SP men. Higher sCD14 levels among SP women correlated with more severe global impairment, and higher viral load measurements correlated with higher monocyte numbers and sCD14 and sCD14 levels, associations that were not observed for SP men. These studies suggest that the risk of developing NCI differ for HIV infected women and men in Nigeria and, for women, may be linked to effects from higher plasma levels of HIV driving activation of circulating monocytes.

Socio-Demographic and Adherence Factors Associated with Viral Load Suppression in HIV-Infected Adults Initiating Therapy in Northern Nigeria: A Randomized Controlled Trial of a Peer Support Intervention.

BACKGROUND: Virological suppression is the main goal of antiretroviral therapy. To achieve this goal, efficient interventions that promote treatment adherence are needed. This study was aimed at exploring the impact of peer-education on virological outcomes in Northern Nigeria. METHODS: A randomized controlled trial (RCT) among patients receiving antiretroviral treatment was conducted in 2 phases between August 2006 and January 2008 in the "largely Muslim" Northern Nigeria. Participants were randomized into one of three intervention arms: standard of care arm, a second arm which included daily reminders via alarm and follow-up calls from peer-educators, and adherence support by a home-based treatment partner; and a third arm which included second arm activities, plus home visits by peer-educators. We evaluated sociodemographic factors and adherence levels, measured using self-report and pharmacy (Rx) refill rates, as risk factors for viral load (VL) suppression. RESULTS: Of the 600 participants (43% males), 276 were observed till the end of the study. There were no significant differences in mean log 10 VL between the intervention groups. At the end of entire follow-up period, 83% (229/276) who were not lost to follow-up achieved undetectable VL (< 400 copies/ml). In the multivariable analysis, age between 30-34 years (vs 18-24 years) and both baseline CD4 ranges between 100-199 cells/mm(3) or 200-349 cells/mm(3) (vs CD4 <100 cells/mm(3)) as positively associated with VL suppression while poor self-reported adherence and <95% Rx refill rates were negatively associated with VL suppression. CONCLUSION: High levels of viral suppression and low prevalence of drug resistance mutations (DRMs) were seen in this cohort participating in an ART adherence study in Northern Nigeria. Self-reported good adherence and optimal Rx refill rates were reported as significant predictors of VL suppression. Our findings indicate that ART adherence will improve significantly regardless of whether HIV-infected adults received peer-education-based medication adherence interventions or standard of care services.

Once-daily antiretroviral therapy among treatment-experienced Muslim patients fasting for the month of Ramadan.

Many countries with a considerable burden of human immunodeficiency virus (HIV) infection in Africa and Asia also have a substantial Muslim population. Anti-retroviral therapy (ART) has led to reductions in HIV morbidity and mortality in those areas. However, for ART to remain durably effective its provision should be adapted to local and religious customary practices such as Ramadan fasting. The fasting is often observed by Muslims with HIV infection and ART might be compromised by sub-optimal adherence during fasting as it precludes the ingestion of oral substances during the daytime and is often associated with an alteration of meals/sleeping patterns. We studied once-daily compared to twice-daily dosed ritonovir boosted lopinavir with fixed-dose tenofovir-emtricitabine once-daily among 17 heavily treatment-experienced stable FT patients in Nigeria. No changes in adherence, diarrhoea, CD4 cell counts, viral load, haematocrit, kidney, liver and lipid tests were observed. Effectiveness, safety and tolerability appeared unaffected by the changes.