Prevalence of pretreatment HIV resistance to integrase inhibitors in West African and Southeast Asian countries.

OBJECTIVES: Integrase strand transfer inhibitors (INSTIs) have been recently recommended as the preferred first-line option for antiretroviral treatment initiators in low- and middle-income countries (LMICs) in response to the growing circulation of resistant HIV to non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this study, we estimated the frequency of pretreatment drug resistance (PDR) to INSTIs in West Africa and Southeast Asia. MATERIALS AND METHODS: Using samples collected from 2015 to 2016, and previously used to assessed PI, NRTI and NNRTI resistance, we generated HIV integrase sequences and identified relevant INSTI PDR mutations using the Stanford and ANRS algorithms. RESULTS: We generated 353 integrase sequences. INSTI PDR frequency was low, 1.1% (4/353) overall, ranging from 0% to 6.3% according to country. However, frequency of PDR to any drug class was very high, 17.9% (95% CI: 13.9%-22.3%), and mostly associated with a high level of NNRTI PDR, 9.7%, and a moderate level of NRTI PDR, 5.3%. CONCLUSIONS: Our results support the recent introduction of INSTIs in LMICs to improve treatment outcome in these settings, but also stress the need for effective actions to prevent uncontrolled emergence of drug resistance to this drug class.

Urban nutrition situation in the slums of three cities in Asia during the COVID-19 pandemic.

Urban-poor households are disproportionately food insecure. The Status and Determinants of Food Insecurity and Undernutrition in Poor Urban Settings (SDFU) cross-sectional surveys were conducted in 2020-2021 to assess the impacts of COVID-19 on food security and diet quality among urban poor women of reproductive age (WRA) and children under 5 (CU5) in Jakarta, Quezon City, and Yangon. Data, collected on food insecurity and child and maternal diet quality using Computer Assisted Telephone Interviewing (CATI), were compared with prepandemic surveys. Prevalence for food insecurity and diet quality indicators were computed. Eight in 10 households in all three cities reported reduced incomes, with 6 in 10 worried about food the previous year. Over 10% of households in all cities substituted nutrient-dense (ND) foods with cheaper alternatives; yet less than 50% of children 6-59 months ate sugar-sweetened beverages or sweet and savoury snacks. Compared with baseline, women's minimum dietary diversity (MDD) in the three cities was significantly lower (up to 30% lower in Yangon and Jakarta), while the prevalence of children (6-23 months) meeting MDD was lower by 17.4%-42.5% in all cities. MDD was attained by >40% of children (24-59 months) in Yangon and Jakarta but only 12.6% in Quezon City. To improve food security and diet quality, multi-sectoral interventions are needed, including distributing ND foods and cash assistance to vulnerable households with CU5 and WRA and delivering targeted nutrition training to encourage appropriate complementary feeding practices and purchasing and consumption of ND foods.

Exploring the magnitude and drivers of the double burden of malnutrition at maternal and dyad levels in peri-urban Peru: A cross-sectional study of low-income mothers, infants and young children.

Multiple forms of malnutrition coexist in Peru, especially in peri-urban areas and poor households. We investigated the magnitude of, and the contribution of, dietary and socio-demographic factors to the double burden of malnutrition (DBM) at maternal (i.e., maternal overweight/obesity with anaemia) and dyad (i.e., maternal overweight/obesity with child anaemia) levels. A cross-sectional survey was conducted among low-income mother-child (6-23 months) dyads (n = 244) from peri-urban communities in Peru. Dietary clusters and the minimum dietary diversity score (MDD) were generated for mothers and infants, respectively. A composite indicator using the maternal dietary clusters and the MDD was created to relate to dyad level DBM. Two dietary clusters were found: (i) the 'high variety (i.e., animal-source foods, fruit and vegetables), high sugary foods/beverages' (cluster 1) and (ii) the 'high potato, low fruit and vegetables, low red meat' (cluster 2). DBM prevalence among mothers and dyads was 19.9% and 36.3%, respectively. Logistic regression analyses revealed that the only socio-demographic factor positively associated with maternal DBM was maternal age (aOR/5 years: 1.35 [1.07, 1.71]). Mothers belonging to diet cluster 1 were less likely to experience the DBM (aOR = 0.52 [0.26, 1.03]), although CIs straddled the null. Socio-demographic factors positively associated with dyad level DBM included maternal age (aOR/5 years: 1.41 [1.15, 1.73]), and having ≥ two children under 5 years (aOR = 2.44 [1.23, 4.84]). Diet was not associated with dyad-level DBM. Double-duty actions that tackle the DBM are needed given that one-third of dyads and a fifth of mothers had concurrent overweight/obesity and anaemia.

Dolutegravir-Based or Low-Dose Efavirenz-Based Regimen for the Treatment of HIV-1.

BACKGROUND: An efavirenz-based regimen (with a 600-mg dose of efavirenz, known as EFV600) was the World Health Organization preferred first-line treatment for human immunodeficiency virus type 1 (HIV-1) infection until June 2018. Given concerns about side effects, dolutegravir-based and low-dose efavirenz-based combinations have been considered as first-line treatments for HIV-1 in resource-limited settings. METHODS: We conducted an open-label, multicenter, randomized, phase 3 noninferiority trial in Cameroon. Adults with HIV-1 infection who had not received antiretroviral therapy and had an HIV-1 RNA level (viral load) of at least 1000 copies per milliliter were randomly assigned to receive either dolutegravir or the reference treatment of low-dose efavirenz (a 400-mg dose, known as EFV400), combined with tenofovir and lamivudine. The primary end point was the proportion of participants with a viral load of less than 50 copies per milliliter at week 48, on the basis of the Food and Drug Administration snapshot algorithm. The difference between treatment groups was calculated, and noninferiority was tested with a margin of 10 percentage points. RESULTS: A total of 613 participants received at least one dose of the assigned regimen. At week 48, a viral load of less than 50 copies per milliliter was observed in 231 of 310 participants (74.5%) in the dolutegravir group and in 209 of 303 participants (69.0%) in the EFV400 group, with a difference of 5.5 percentage points (95% confidence interval [CI], -1.6 to 12.7; P<0.001 for noninferiority). Among those with a baseline viral load of at least 100,000 copies per milliliter, a viral load of less than 50 copies per milliliter was observed in 137 of 207 participants (66.2%) in the dolutegravir group and in 123 of 200 participants (61.5%) in the EFV400 group, with a difference of 4.7 percentage points (95% CI, -4.6 to 14.0). Virologic failure (a viral load of >1000 copies per milliliter) was observed in 3 participants in the dolutegravir group (with none acquiring drug-resistance mutations) and in 16 participants in the EFV400 group. More weight gain was observed in the dolutegravir group than in the EFV400 group (median weight gain, 5.0 kg vs. 3.0 kg; incidence of obesity, 12.3% vs. 5.4%). CONCLUSIONS: In HIV-1-infected adults in Cameroon, a dolutegravir-based regimen was noninferior to an EFV400-based reference regimen with regard to viral suppression at week 48. Among participants who had a viral load of at least 100,000 copies per milliliter when antiretroviral therapy was initiated, fewer participants than expected had viral suppression. (Funded by Unitaid and the French National Agency for AIDS Research; NAMSAL ANRS 12313 ClinicalTrials.gov number, NCT02777229.).

Prevention of mother-to-child transmission of HIV at the second immunization visit: a cross-sectional study, Burkina Faso.

Objective: To evaluate the performance of the cascade of activities for prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) at the second immunization visit in Burkina Faso. Methods: In a cross-sectional study, we recruited mothers attending the second immunization visit for their infant in 20 health centres of Bobo-Dioulasso city, Burkina Faso over 12 months (2019-2020). We administered a short questionnaire to 14 176 mothers and performed HIV serological tests on mothers who had not been tested in the last 3 months. All mothers were asked about their attendance for antenatal care and HIV rapid testing. HIV-infected mothers were also asked about the timing of their HIV diagnosis, antiretroviral therapy, pre-exposure prophylaxis initiation at birth and infant diagnosis of HIV. Findings: Of 14 136 respondents, 13 738 (97.2%) had at least one HIV serological test in their lifetime. Of 13 078 mothers who were never tested or were HIV-negative, 12 454 (95.2%) were tested during or after their last pregnancy. Among HIV-infected mothers already aware of their status, 110/111 (99.1%) women were on antiretroviral therapy. Among HIV-exposed infants, 84/101 (83.2%) babies received 6 weeks of antiretroviral prophylaxis at birth and 58/110 (52.7%) had a blood sample collected for early infant diagnosis. Only two mothers received their child's test results at the time of the second immunization visit. Four mothers were newly diagnosed as HIV-positive during the study. Conclusion: Collecting data at the second immunization visit, a visit rarely missed by mothers, could be useful for identifying gaps in the PMTCT cascade in settings where mothers are difficult to reach, such as in low-income countries with intermediate or low HIV prevalence.

Diet and food insecurity among mothers, infants, and young children in Peru before and during COVID-19: A panel survey.

The COVID-19 pandemic may impact diet and nutrition through increased household food insecurity, lack of access to health services, and poorer quality diets. The primary aim of this study is to assess the impact of the pandemic on dietary outcomes of mothers and their infants and young children (IYC) in low-income urban areas of Peru. We conducted a panel study, with one survey prepandemic (n = 244) and one survey 9 months after the onset of COVID-19 (n = 254). We assessed breastfeeding and complementary feeding indicators and maternal dietary diversity in both surveys. During COVID-19, we assessed household food insecurity experience and economic impacts of the pandemic on livelihoods; receipt of financial or food assistance, and uptake of health services. Almost all respondents (98.0%) reported adverse economic impacts due to the pandemic and 46.9% of households were at risk of moderate or severe household food insecurity. The proportion of households receiving government food assistance nearly doubled between the two surveys (36.5%-59.5%). Dietary indicators, however, did not worsen in mothers or IYC. Positive changes included an increase in exclusive breastfeeding <6 months (24.2%-39.0%, p < 0.008) and a decrease in sweet food consumption by IYC (33.1%-18.1%, p = 0.001) and mothers (34.0%-14.6%, p < 0.001). The prevalence of sugar-sweetened beverage consumption remained high in both mothers (97%) and IYC (78%). In sum, we found dietary indicators had not significantly worsened 9 months into the COVID-19 pandemic. However, several indicators remain suboptimal and should be targeted in future interventions.

Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial).

BACKGROUND: The ANRS12286/MOBIDIP trial showed that boosted protease inhibitor (bPI) plus lamivudine dual therapy was superior to bPI monotherapy as maintenance treatment in subjects with a history of M184V mutation. OBJECTIVES: We aimed to deep analyse the detection of M184V/I variants at time of switch and at the time of virological failure (VF). METHODS: Ultra-deep sequencing (UDS) was performed on proviral HIV-DNA at inclusion among 265 patients enrolled in the ANRS 12026/MOBIDIP trial, and on plasma from 31 patients experiencing VF. The proportion of M184V/I variants was described and the association between the M184V/I mutation at 1% of threshold and VF was explored with logistic regression models. RESULTS: M184V and I mutations were detected in HIV-DNA for 173/252 (69%) and 31/252 (12%) of participants, respectively. Longer duration of first-line treatment, higher plasma viral load at first-line treatment failure and higher baseline HIV-DNA load were associated with the archived M184V. M184I mutation was always associated with a STOP codon, suggesting defective virus. The 48 week estimated probability of remaining free from VF was comparable with or without the M184V/I mutation for dual therapy. At failure, M184V and major PI mutations were detected in 1/17 and 5/15 patients in the bPI arm and in 2/2 and 0/3 in the bPI+lamivudine arm, respectively. CONCLUSIONS: Using UDS evidenced that archiving of M184V in HIV-DNA is heterogeneous despite past historical M184V in 96% of cases. The antiviral efficacy of lamivudine-based dual therapy regimens is mainly due to the residual lamivudine activity.

Increased Prevalence of Neurocognitive Impairment in Aging People Living With Human Immunodeficiency Virus: The ANRS EP58 HAND 55-70 Study.

BACKGROUND: There are limited data on the comparative prevalence of neurocognitive impairment (NCI) in aging people living with human immunodeficiency virus (PLHIV) and people not living with HIV. METHODS: This was a cross-sectional study of PLHIV randomly matched by age (±4 years), gender, and education with 5 HIV-uninfected individuals from the CONSTANCES cohort. PLHIV were fluent in French and sequentially included during routine outpatient visits if aged 55-70 years, with HIV viral load <50 copies/mL, and lymphocyte T-CD4 level ≥200 cells/µL in the past 24 and 12 months, respectively. The primary outcome was NCI as defined by the Frascati criteria. Multivariate normative comparison (MNC) and -1.5 standard deviations in ≥2 neurocognitive domains were secondary outcomes of NCI. RESULTS: Two hundred PLHIV were matched with 1000 controls. Median age was 62 years, and 85% were men. In PLHIV, the median T-CD4 lymphocyte level was 650 cells/µL, and median nadir T-CD4 lymphocyte level was 176 cells/µL. NCI was found in 71 (35.5%) PLHIV and in 242 (24.2%) controls (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.25, 2.41). After adjusting for confounders, HIV remained significantly associated with NCI (OR, 1.50; 95% CI, 1.04, 2.16). Adjusted results were similar with NCI defined by MNC (ORMNC, 2.95; 95% CI, 1.13, 3.50) or -1.5 SD (OR-1.5, 2.24; 95% CI, 1.39, 3.62). CONCLUSIONS: In this matched study of aging individuals, HIV was significantly associated with an increased risk of NCI after adjusting for major confounders. Results were confirmed with more stringent NCI classifications. CLINICAL TRIALS REGISTRATION: NCT02592174.

Lopinavir-Ritonavir Impairs Adrenal Function in Infants.

BACKGROUND: Perinatal treatment with lopinavir boosted by ritonavir (LPV/r) is associated with steroidogenic abnormalities. Long-term effects in infants have not been studied. METHODS: Adrenal-hormone profiles were compared at weeks 6 and 26 between human immunodeficiency virus (HIV)-1-exposed but uninfected infants randomly assigned at 7 days of life to prophylaxis with LPV/r or lamivudine (3TC) to prevent transmission during breastfeeding. LPV/r in vitro effect on steroidogenesis was assessed in H295R cells. RESULTS: At week 6, 159 frozen plasma samples from Burkina Faso and South Africa were assessed (LPV/r group: n = 92; 3TC group: n = 67) and at week 26, 95 samples from Burkina Faso (LPV/r group: n = 47; 3TC group: n = 48). At week 6, LPV/r-treated infants had a higher median dehydroepiandrosterone (DHEA) level than infants from the 3TC arm: 3.91 versus 1.48 ng/mL (P < .001). Higher DHEA levels (>5 ng/mL) at week 6 were associated with higher 17-OH-pregnenolone (7.78 vs 3.71 ng/mL, P = .0004) and lower testosterone (0.05 vs 1.34 ng/mL, P = .009) levels in LPV/r-exposed children. There was a significant correlation between the DHEA and LPV/r AUC levels (ρ = 0.40, P = .019) and Ctrough (ρ = 0.40, P = .017). At week 26, DHEA levels remained higher in the LPV/r arm: 0.45 versus 0.13 ng/mL (P = .002). Lopinavir, but not ritonavir, inhibited CYP17A1 and CYP21A2 activity in H295R cells. CONCLUSIONS: Lopinavir was associated with dose-dependent adrenal dysfunction in infants. The impact of long-term exposure and potential clinical consequences require evaluation. CLINICAL TRIALS REGISTRATION: NCT00640263.

Multimorbidity in Elderly Persons According to the Year of Diagnosis of Human Immunodeficiency Virus Infection: A Cross-sectional Dat'AIDS Cohort Study.

BACKGROUND: We assessed prevalence of multimorbidity (MM) according to year of human immunodeficiency virus (HIV) diagnosis in elderly people living with HIV (PLWH). METHODS: This was a cross-sectional study of MM in PLWH aged ≥70 years from the Dat'AIDS French multicenter cohort. MM was defined as at least 3 coexistent morbidities of high blood pressure, diabetes mellitus, osteoporosis, non-AIDS cancer, chronic renal failure, cardiovascular and cerebrovascular disease, obesity, undernutrition, or hypercholesterolemia. Logistic regression models evaluated the association between MM and calendar periods of HIV diagnosis (1983-1996, 1997-2006, and 2007-2018). The secondary analysis evaluated MM as a continuous outcome, and a sensitivity analysis excluded PLWH with nadir CD4 count <200 cells/µL. RESULTS: Between January 2017 and September 2018, 2476 PLWH were included. Median age was 73 years, 75% were men, median CD4 count was 578 cells/µL, and 94% had controlled viremia. MM prevalence was 71%. HBP and hypercholesterolemia were the most prevalent comorbidities. After adjustment for age, gender, smoking status, hepatitis C and hepatitis B virus coinfection, group of exposure, nadir CD4 count, CD4:CD8 ratio, and last CD4 level, calendar period of diagnosis was not associated with MM (P = .169). MM was associated with older age, CD4/CD8 ratio <0.8, and nadir CD4 count <200 cells/µL. Similar results were found with secondary and sensitivity analyses. CONCLUSIONS: MM prevalence was high and increased with age, low CD4/CD8 ratio, and nadir CD4 count <200 cells/µL but was not associated with calendar periods of HIV diagnosis. Known duration of HIV diagnosis does not seem to be a criterion for selecting elderly PLWH at risk of MM.

Hepatitis B testing, treatment, and virologic suppression in HIV-infected patients in Cameroon (ANRS 12288 EVOLCAM).

BACKGROUND: Hepatitis B is a major concern in Africa, especially in HIV-infected patients. Unfortunately, access to hepatitis B virus (HBV) testing and adequate treatment remains a challenge in the continent. We investigated HBV testing, treatment, and virologic suppression in HIV-infected patients followed up as part of Cameroon's national antiretroviral programme. METHODS: A cross-sectional survey was performed in adult patients receiving antiretroviral therapy (ART) in 19 hospitals in the Centre and Littoral regions in Cameroon. The proportions of patients tested for hepatitis B surface antigen (HBsAg) prior to the study were compared among all study hospitals using the Chi-square test. The association of individual and hospital-related characteristics with HBV testing and virologic suppression was assessed using multilevel logistic regression models. RESULTS: Of 1706 patients (women 74%, median age 42 years, median time on ART 3.9 years), 302 (17.7%) had been tested for HBsAg prior to the study. The proportion of HBV-tested patients ranged from 0.8 to 72.5% according to the individual hospital (p < 0.001). HBV testing was lower in women (adjusted odds ratio [aOR] 0.64, 95% confidence interval [CI] 0.46-0.89, p = 0.010) and higher in patients who initiated ART in 2010 or later (aOR 1.66, 95% CI 1.23-2.27, p < 0.001). Of 159 HBsAg-positive patients at the time of the study (9.3%), only 97 (61.0%) received Tenofovir + Lamivudine (or Emtricitabine). Of 157 coinfected patients, 114 (72.6%) had a HBV viral load < 10 IU/mL. HBV suppression was higher in patients with a HIV viral load < 300 copies/mL (aOR 3.46, 95% CI 1.48-8.09, p = 0.004) and lower in patients with increased ALT level (aOR 0.86 per 10 IU/mL increase, 95% CI 0.75-0.97, p = 0.019). CONCLUSIONS: A substantial proportion of HIV/HBV coinfected patients were at higher risk of liver disease progression. Improving the management of HBV infection in the routine healthcare setting in Africa is urgently required in order to achieve the 2030 elimination targets. Micro-elimination of HBV infection in people living with HIV could be an easier and cost-effective component than more widely scaling up HBV policies.

Prevalence of pretreatment HIV drug resistance in West African and Southeast Asian countries.

Background: ART in the developing world has moved to a new era with the WHO recommendation to test and immediately treat HIV-positive individuals. A high frequency of pretreatment HIV drug resistance (PDR) can compromise ART efficacy. Our study presents updated estimates of PDR in seven countries from West Africa (Burkina Faso, Cameroon, Côte d'Ivoire, Mali and Togo) and Southeast Asia (Thailand and Vietnam). Methods: Eligible study participants were adult ART initiators, recruited from December 2015 to November 2016 in major ART clinics in each country. HIV drug resistance (HIVDR) tests were performed for all specimens and interpretation was done using the Stanford algorithm. Results: Overall, 1153 participants were recruited and 1020 nt sequences were generated. PDR frequency among all initiators was 15.9% (95% CI: 13.8%-18.3%) overall, ranging from 9.6% and 10.2% in Burkina Faso and Thailand, respectively, 14.7% in Vietnam, 15.4% in Mali, 16.5% in Côte d'Ivoire and 19.3% in Cameroon, to 24.6% in Togo. The prevalence of NNRTI resistance mutations was 12%; NRTI and PI PDR prevalences were 4% and 3%, respectively. Conclusions: Our study shows that in most countries PDR exceeded 10%, warranting the conduct of nationally representative surveys to confirm this trend. In the meantime, actions to prevent drug resistance, including transition from NNRTIs to more robust drug classes should be urgently implemented.

Prevalence of pretreatment HIV drug resistance in Cameroon following a nationally representative WHO survey.

Background: Pretreatment HIV drug resistance (PDR) has the potential to affect treatment outcome and mortality. We present here the first nationally representative PDR study conducted in Cameroon. Methods: From February to July 2015, HIV-infected ART initiators were recruited from 24 randomly selected clinics situated in both urban and rural regions. Dried blood spot specimens were collected from study participants at these clinics and centralized in a reference laboratory in Yaoundé, Cameroon, for drug resistance testing. HIV drug resistance mutations were identified using the Stanford algorithm. Results: Overall, from the 379 participants recruited, 321 pol sequences were successfully interpreted. Two hundred and five sequences were from patients attending urban ART clinics and 116 from patients seen at rural facilities. Nine percent of sequences (29/321) were from participants reporting previous exposure to antiretrovirals. PDR prevalence among all initiators was 10.4% (95% CI 5.4%-19.1%), with 14.2% (95% CI 6.6%-27.9%) reported in urban areas and 4.3% (95% CI 1.2%-14.3%) in rural areas. Among participants with no prior exposure to antiretrovirals, PDR prevalence was 10.4% (95% CI 4.7%-21.5%) overall, with 13.5% (95% CI 5.1%-31.5%) and 5.3% (95% CI 1.4%-17.5%) reported in urban and rural areas, respectively. Conclusions: Our findings indicate that at least 10% of patients initiating ART in Cameroon carry viruses with PDR and may be at risk of premature ART failure. The high level of NNRTI-associated resistance is of particular concern and supports introduction of drugs with a higher genetic barrier to resistance.

Tenofovir plasma concentrations related to estimated glomerular filtration rate changes in first-line regimens in African HIV-infected patients: ANRS 12115 DAYANA substudy.

OBJECTIVES: An open-label randomized trial (DAYANA) was conducted in sub-Saharan settings to evaluate four different regimens containing tenofovir disoproxil fumarate as first-line treatment for HIV infection. The objectives of the present substudy were to assess the relationship between trough concentrations of tenofovir in plasma collected after 24 h (C24) and estimated glomerular filtration rates (eGFR) calculated by the different formulae that are available. METHODS: The criteria for eligibility were those of the DAYANA trial, recruiting naive patients. The four tenofovir regimens were: Group 1, tenofovir/emtricitabine/nevirapine; Group 2, tenofovir/lopinavir/ritonavir; Group 3, tenofovir/emtricitabine/zidovudine; and Group 4, tenofovir/emtricitabine/efavirenz. The C24 of tenofovir was determined using LC-MS/MS. The eGFR was calculated using the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae. RESULTS: The median C24 of tenofovir was 42 ng/mL. The C24 of tenofovir was higher with lopinavir/ritonavir than with the other three regimens: at Week 4, 84 ng/mL versus 25 ng/mL; and at Week 48, 81 ng/mL versus 52 ng/mL. The baseline merged eGFR was 98.2 mL/min/1.73 m(2) with the CKD-EPI equation. Only the mean changes in eGFR in Group 2 differed from the absolute value of zero (-8.2 mL/min/1.73 m(2)) with the CKD-EPI equation between baseline and Week 48. The Cockcroft-Gault formula is inappropriate for these African patients because it underestimated the baseline eGFR and overestimated the changes in eGFR between baseline and Week 48. CONCLUSIONS: In this population of mostly female HIV-1-infected African patients, tenofovir plasma overexposure was associated with PI/ritonavir and a time-dependent decrease in eGFR, probably via an inhibition of MRP2/MRP4 efflux transporters. The close monitoring over time of the eGFR using MDRD or CKD-EPI calculations and by using other biomarkers of renal disorder should be proposed as an alternative to therapeutic drug monitoring in resource-limited countries.

Abdominal vs. overall obesity among women in a nutrition transition context: geographic and socio-economic patterns of abdominal-only obesity in Tunisia.

BACKGROUND: Most assessments of the burden of obesity in nutrition transition contexts rely on body mass index (BMI) only, even though abdominal adiposity might be specifically predictive of adverse health outcomes. In Tunisia, a typical country of the Middle East and North Africa (MENA) region, where the burden of obesity is especially high among women, we compared female abdominal vs. overall obesity and its geographic and socio-economic cofactors, both at population and within-subject levels. METHODS: The cross-sectional study used a stratified, three-level, clustered sample of 35- to 70-year-old women (n = 2,964). Overall obesity was BMI = weight/height(2) ≥ 30 kg/m(2) and abdominal obesity waist circumference ≥ 88 cm. We quantified the burden of obesity for overall and abdominal obesity separately and their association with place of residence (urban/rural, the seven regions that compose Tunisia), plus physiological and socio-economic cofactors by logistic regression. We studied the within-subject concordance of the two obesities and estimated the prevalence of subject-level "abdominal-only" obesity (AO) and "overall-only" obesity (OO) and assessed relationships with the cofactors by multinomial logistic regression. RESULTS: Abdominal obesity was much more prevalent (60.4% [57.7-63.0]) than overall obesity (37.0% [34.5-39.6]), due to a high proportion of AO status (25.0% [22.8-27.1]), while the proportion of OO was small (1.6% [1.1-2.2]). We found mostly similar associations between abdominal and overall obesity and all the cofactors except that the regional variability of abdominal obesity was much larger than that of overall obesity. There were no adjusted associations of AO status with urban/rural area of residence (P = 0.21), education (P = 0.97) or household welfare level (P = 0.94) and only non-menopausal women (P = 0.093), lower parity women (P = 0.061) or worker/employees (P = 0.038) were somewhat less likely to be AO. However, there was a large residual adjusted regional variability of AO status (from 16.6% to 34.1%, adjusted P < 0.0001), possibly of genetic, epigenetic, or developmental origins. CONCLUSION: Measures of abdominal adiposity need to be included in population-level appraisals of the burden of obesity, especially among women in the MENA region. The causes of the highly prevalent abdominal-only obesity status among women require further investigation.

Extraordinary heterogeneity of virological outcomes in patients receiving highly antiretroviral therapy and monitored with the World Health Organization public health approach in sub-saharan Africa and southeast Asia.

BACKGROUND: The limited access to virological monitoring in developing countries is a major weakness of the current antiretroviral treatment (ART) strategy in these settings. We conducted a large cross-sectional study in Burkina Faso, Cameroon, Cote d'Ivoire, Senegal, Togo, Thailand, and Vietnam to assess virological failure and drug resistance mutations (DRMs) after 12 or 24 months of ART. METHODS: Between 2009 and 2011, we recruited adults attending ART centers 10-14 months (the M12 group) or 22-26 months (M24 group) after initiating ART. Demographic and clinical data were collected on site, and viral load was measured. Samples with a viral load of ≥ 1000 copies/mL, considered as the failure threshold, were genotyped for drug resistance assessment. RESULTS: Overall, 3935 patients were recruited (2060 at M12 and 1875 at M24). Median ages varied from 32 to 42 years. Median CD4(+) T-cell counts at ART initiation were low (99-172 cells/µL). The main ART regimens included stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. Overall, virological failure frequency was 11.1% for M12 patients and 12.4% for M24 patients, and 71.0% to 86.1% of these patients, respectively, had drug-resistant virus. Across sites, virological failure varied from 2.9% to 20.6% in M12 patients and from 3.7% to 26.0% in M24 patients. Predominant DRMs were associated with ART regimens, but virus in several patients accumulated DRMs to drugs not received, such as abacavir, didanosine, tenofovir, etravirine, and rilpivirine. CONCLUSIONS: Our findings show heterogeneous virological failure and illustrate that, in addition to routine access to viral load, good management of ART programs is even more critical to improve treatment outcomes in resource-limited countries.

Field evaluation of dried blood spots for routine HIV-1 viral load and drug resistance monitoring in patients receiving antiretroviral therapy in Africa and Asia.

Dried blood spots (DBS) can be used in developing countries to alleviate the logistic constraints of using blood plasma specimens for viral load (VL) and HIV drug resistance (HIVDR) testing, but they should be assessed under field conditions. Between 2009 and 2011, we collected paired plasma-DBS samples from treatment-experienced HIV-1-infected adults in Burkina Faso, Cameroon, Senegal, Togo, Thailand, and Vietnam. The DBS were stored at an ambient temperature for 2 to 4 weeks and subsequently at -20°C before testing. VL testing was performed on the plasma samples and DBS using locally available methods: the Abbott m2000rt HIV-1 test, generic G2 real-time PCR, or the NucliSENS EasyQ version 1.2 test. In the case of virological failure (VF), i.e., a plasma VL of ≥1,000 copies/ml, HIVDR genotyping was performed on paired plasma-DBS samples. Overall, we compared 382 plasma-DBS sample pairs for DBS VL testing accuracy. The sensitivities of the different assays in different laboratories for detecting VF using DBS varied from 75% to 100% for the m2000rt test in labs B, C, and D, 91% to 93% for generic G2 real-time PCR in labs A and F, and 85% for the NucliSENS test in lab E. The specificities varied from 82% to 97% for the m2000rt and NucliSENS tests and reached only 60% for the generic G2 test. The NucliSENS test showed good agreement between plasma and DBS VL but underestimated the DBS VL. The lowest agreement was observed for the generic G2 test. Genotyping was successful for 96/124 (77%) DBS tested, and 75/96 (78%) plasma-DBS pairs had identical HIVDR mutations. Significant discrepancies in resistance interpretations were observed in 9 cases, 6 of which were from the same laboratory. DBS can be successfully used as an alternative to blood plasma samples for routine VL and HIVDR monitoring in African and Asian settings. However, the selection of an adequate VL measurement method and the definition of the VF threshold should be considered, and laboratory performance should be monitored.

Defining a Dichotomous Indicator for Population-Level Assessment of Dietary Diversity Among Pregnant Adolescent Girls and Women: A Secondary Analysis of Quantitative 24-h Recalls from Rural Settings in Bangladesh, Burkina Faso, India, and Nepal.

Background: The Minimum Dietary Diversity for Women of Reproductive Age (MDD-W) indicator was validated as a proxy of micronutrient adequacy among nonpregnant women in low- and middle-income countries (LMICs). At that time, indeed, there was insufficient data to validate the indicator among pregnant women, who face higher micronutrient requirements. Objective: This study aimed to validate a minimum food group consumption threshold, out of the 10 food groups used to construct MDD-W, to be used as a population-level indicator of higher micronutrient adequacy among pregnant women aged 15-49 y in LMICs. Methods: We used secondary quantitative 24-h recall data from 6 surveys in 4 LMICs (Bangladesh, Burkina Faso, India, and Nepal, total n = 4909). We computed the 10-food group Women's Dietary Diversity Score (WDDS-10) and calculated the mean probability of adequacy (MPA) of 11 micronutrients. Linear regression models were fitted to assess the associations between WDDS-10 and MPA. Sensitivity, specificity, and proportion of individuals correctly classified were used to assess the performance of MDD-W in predicting an MPA of >0.60. Results: In the pooled sample, median values (interquartile range) of WDDS-10 and MPA were 3 (1) and 0.20 (0.34), respectively, whereas the proportion of pregnant women with an MPA of >0.60 was 9.6%. The WDDS-10 was significantly positively associated with MPA in each survey. Although the acceptable food group consumption threshold varied between 4 and 6 food groups across surveys, the threshold of 5 showed the highest performance in the pooled sample with good sensitivity (62%), very good specificity (81%), and percentage of correctly classified individuals (79%). Conclusions: The WDDS-10 is a good predictor of dietary micronutrient adequacy among pregnant women aged 15-49 y in LMICs. Moreover, the threshold of 5 or more food groups for the MDD-W indicator may be extended to all women of reproductive age, regardless of their physiologic status.

Corrigendum to 'Defining a Dichotomous Indicator for Population-Level Assessment of Dietary Diversity Among Pregnant Adolescent Girls and Women: ' [Curr. Dev. Nutr. 8 (2024) 102053].

[This corrects the article DOI: 10.1016/j.cdnut.2023.102053.].

Single real-time reverse transcription-PCR assay for detection and quantification of genetically diverse HIV-1, SIVcpz, and SIVgor strains.

Although antiretroviral treatment availability has improved, the virological monitoring of patients remains largely uneven across regions. In addition, viral quantification tests are suffering from human immunodeficiency virus type 1 (HIV-1) genetic diversity, fueled by the emergence of new recombinants and of lentiviruses from nonhuman primates. We developed a real-time reverse transcription-PCR (RT-PCR) assay that is relatively inexpensive and able to detect and quantify all circulating forms of HIV-1 and its simian immunodeficiency virus (SIV) precursors, SIVcpz and SIVgor. Primers and a probe were designed to detect all variants of the HIV-1/SIVcpz/SIVgor lineage. HIV-1 M plasma (n = 190; 1.68 to 7.78 log(10) copies/ml) representing eight subtypes, nine circulating recombinant forms, and 21 unique recombinant forms were tested. The mean PCR efficiency was 99%, with low coefficients of intra- and interassay variation (<5%) and a limit of quantification of <2.50 log(10) copies/ml, with a 200-µl plasma volume. On the studied range, the specificity and the analytical sensitivity were 100 and 97.4%, respectively. The viral loads were highly correlated (r = 0.95, P < 0.0001) with the reference method (generic HIV assay; Biocentric) and had no systematic difference, irrespective of genotype. Furthermore, 22 HIV-1 O plasmas were screened and were better quantified compared to the gold-standard RealTime HIV-1 assay (Abbott), including four samples that were only quantified by our assay. Finally, we could quantify SIVcpzPtt and SIVcpzPts from chimpanzee plasma (n = 5) and amplify SIVcpz and SIVgor from feces. Thus, the newly developed real-time RT-PCR assay detects and quantifies strains from the HIV-1/SIVcpz/SIVgor lineage, including a wide diversity of group M strains and HIV-1 O. It can therefore be useful in geographical areas of high HIV diversity and at risk for the emergence of new HIV variants.