Enhanced adherence counselling outcomes among people living with HIV with virological failure: Single-centre experience in Pune, India.

OBJECTIVES: World Health Organization has recommended enhanced adherence counselling (EAC) for people living with HIV (PLHIV) with virological failure. This study aimed to assess the outcomes of EAC and its associated factors among PLHIV with virological failure. METHODS: Data collected between March 2020 and February 2022 on viral load (VL) testing at antiretroviral therapy (ART) centre in Pune, India were reviewed. PLHIV with viral load ≥1000 copies/ml followed by three EAC sessions and a repeat viral load test were included. Multivariate logistic regression analysis was used to assess the factors associated with virological suppression (<1000 copies/ml). RESULTS: Of 170 PLHIV, 81 (47.6%) showed virological suppression. Being literate (p = 0.027), females (p = 0.021), on second-line ART regimen (p = 0.020), and with EAC initiation within a month (p = 0.016) were significantly associated with virological suppression. No association was found between reported barriers to treatment adherence and virological suppression. DISCUSSION: Early initiation of EAC is crucial for virological suppression among PLHIV with high viral load. It is important to highlight the significance of treatment adherence among individuals on first-line ART regimen. The use of effective visual tools during EAC sessions may help in achieving virological suppression among those with low literacy.

Dynamics of Matricellular Protein Levels in Blood Predict Recovery in Patients with Human Immunodeficiency Virus-Tuberculosis Coinfection.

Chronic immune activation in tuberculosis (TB) associated with human immunodeficiency virus (HIV) infection (HIV/TB) modifies their clinical course. We prospectively measured osteopontin (OPN), full-length galectin-9 (FL-Gal9), and total-Gal9 (T-Gal9) levels in 32 patients with HIV/TB coinfection treated with anti-tuberculosis and antiretroviral therapies over 6-18 months to determine the amelioration of inflammatory conditions in response to the therapies. We observed a significant time-dependent decrease in FL-Gal9 in both pulmonary TB (PTB, n = 20) and extrapulmonary TB (EPTB, n = 12) patients. The levels of T-Gal9, OPN, and CRP decreased significantly after treatment in only PTB patients. We calculated the inflammatory score (INS) indicating immunologic recovery based on the decline in OPN, FL-Gal9, T-Gal9, and CRP levels. Baseline levels of T-Gal9 and OPN positively correlated with INS in all TB and only PTB patients, respectively, indicating that their levels predict better recovery. In contrast, FL-Gal9 levels at the second visit negatively correlated with INS in EPTB patients. The decrease rate in OPN levels at the second visit also correlated positively with INS in PTB patients. Women showed a higher INS and lower levels of FL-Gal9 than men. The patients with moderate grade severity on chest X-ray had higher CD4 cell numbers than those with limited grade severity. Monitoring these markers will help to predict and assess the response to therapy as well as to devise strategies to reduce the complications caused by chronic immune activation in patients with HIV/TB coinfection.

Monocyte to lymphocyte ratio and hemoglobin level to predict tuberculosis after antiretroviral therapy initiation.

OBJECTIVE: To determine the performance of the baseline monocyte to lymphocyte ratio (MLR), baseline anemia severity and combination of these biomarkers, to predict tuberculosis (TB) incidence in people with HIV (PWH) after antiretroviral therapy (ART) initiation. DESIGN: Multicenter, retrospective cohort study. METHODS: We utilized the data from study A5175 (Prospective Evaluation of Antiretroviral Therapy in Resource-limited Settings: PEARLS). We assessed the utility of MLR, anemia severity and in combination, for predicting TB in the first year after ART. Cox regression was used to assess associations of MLR and anemia with incident TB. Harrell's C index was used to describe single model discrimination. RESULTS: A total of 1455 participants with a median age of 34 [interquartile range (IQR) 29, 41] were included. Fifty-four participants were diagnosed with TB. The hazard ratio (HR) for incident TB was 1.77 [95% confidence interval (CI) 1.01-3.07]; P  = 0.04 for those with MLR ≥0.23. The HR for mild/mod anemia was 3.35 (95% CI 1.78-6.29; P  < 0.001) and 18.16 (95% CI 5.17-63.77; P  < 0.001) for severe anemia. After combining parameters, there were increases in adjusted HR (aHR) for MLR ≥0.23 to 1.83 (95% CI 1.05-3.18), and degrees of anemia to 3.38 (95% CI 1.80-6.35) for mild/mod anemia and 19.09 (95% CI 5.43-67.12) for severe anemia. CONCLUSIONS: MLR and hemoglobin levels which are available in routine HIV care can be used at ART initiation for identifying patients at high risk of developing TB disease to guide diagnostic and management decisions.

Antiretroviral Treatment-Induced Galectin-9 Might Impact HIV Viremia in Addition to Contributing to Inflammaging.

BACKGROUND: Galectin-9 induces HIV reactivation and also contributes to non-AIDS events through inflammaging. Hence, it is important to assess its levels in HIV-infected individuals to determine their association with HIV viremia and other comorbidities. METHODS: Plasma galectin-9 levels were estimated in viremic (n = 152) and aviremic (n = 395) individuals on first-line antiretroviral therapy (ART). They were assessed for correlation with HIV-1 viral load (VL), CD4 count, and ART duration, as well as for receiver operating characteristic curve analysis. RESULT: Plasma galectin-9 levels correlated positively with VL (r = 0.507, p < 0.0001) and ART duration (r = 0.308, p = 0.002) and negatively with CD4 count (r = -0.186, p < 0.0001). Area under the curve for galectin-9/CD4 count ratio for identifying viremic individuals was 0.906. Sensitivity and specificity of the ratio at a cutoff of 14.47 were 90.13% and 70.05%, respectively, for detecting viremic individuals. Further, galectin-9 levels correlated with cystatin C (r = 0.239, p = 0.0183), IL-18 (r = 0.311, p = 0.006), and systolic blood pressure (r = 0.220, p = 0.0355). Galectin-9-induced HIV reactivation was significantly lower in individuals on long-term ART than those on short-term ART. CONCLUSION: The galectin-9-to-CD4 count ratio indicated the potential of galectin-9 as a cheaper monitoring tool to detect HIV viremia. Strategies for countering the effects of galectin-9 for controlling HIV viremia and non-AIDS events are urgently warranted.

A protocol for feasibility of plasma based GeneXpert platform and Dried Blood Spot (DBS) based Abbott platform for HIV-1 viral load testing among the people living with HIV attending ART centers in India.

BACKGROUND: HIV-1 Viral load (VL) measures efficiency of the antiretroviral therapy (ART) after treatment initiation and helps to diagnose virological failures at an early stage. Current VL assays require sophisticated laboratory facilities. As well as there are other challenges pertaining to insufficient laboratory access, cold-chain management and sample transportation. Hence the number of HIV-1 VL testing laboratories is inadequate in the resource limited settings. The revised national tuberculosis elimination programme (NTEP) in India has developed a vast network of point of care (PoC) testing facilities for diagnosis of tuberculosis and several GeneXpert platforms are functional under this programme. Both the GeneXpert HIV-1 assay and HIV-1 Abbott real time assay are comparable and GeneXpert HIV-1 assay can be used as PoC for HIV-1 Viral load testing. Also, the dried blood spot (DBS) as a sample type has been considered as a good option for HIV-1 VL testing in hard to reach areas. This protocol is therefore developed to assess the feasibility of integrating HIV-1 VL testing among people living with HIV (PLHIV) attending ART centres using the two public health models under the current programme: 1. HIV-1 VL testing using GeneXpert platform and plasma as a sample type, and 2. HIV-1 VL testing using Abbott m2000 platform and DBS as a sample type. METHODS: This ethically approved feasibility study will be implemented at two moderate to high burden ART centres where VL testing facility is not available in the town. Under Model-1, arrangements will be made to carry out VL testing on the adjacent GeneXpert facility and under Model-2, DBS will be prepared on site and couriered to identified viral load testing laboratories. In order to assess the feasibility, data will be collected on pretested questionnaire pertaining to number of samples tested for VL testing, number of samples tested for tuberculosis (TB) diagnosis and the turnaround time (TAT). In-depth interviews will be conducted among the service providers at ART centre and different laboratories for addressing any issues regarding the model implementation. RESULTS: The proportion of PLHIV tested for VL at ART centres, total TAT for both models including TAT for sample transportation, sample testing and receipt of results as well as proportion of sample rejections and reasons for the same, correlation coefficient between DBS based and plasma based VL testing will be estimated using various statistical tools. CONCLUSION: If found promising, these public health approaches will be helpful for the policy makers and program implementation in scaling up HIV-1 viral load testing within India.

Metabolic syndrome in people living with antiretroviral therapy: A cross-sectional investigation from Pune, India.

Background: Improved longevity of people living with HIV on highly active antiretroviral therapy and accelerated aging processes are considered contributory to Metabolic Syndrome. Objectives: The current study investigated metabolic syndrome (MetS) in people living with HIV (PLH) who were receiving antiretroviral therapy (ART) under the ongoing National AIDS Control Program. Methods: Clinic attendees (n = 3088) who were on ART for more than 6 months constituted the sampling frame, from which 378 study participants were randomly drawn and included in the analysis following the eligibility check. One hundred and fifty-nine clinic attendees, initiated on ART in ≤6 months, provided an opportunity to estimate the prevalence of MetS in them. Sixty-two PLH from this smaller group were enrolled. Results: MetS was found among 19% (73/378; 95% confidence interval [CI] 15.5%-23.7%) PLH who were on ART >6 months compared with 24% (15/62; 95% CI 14.2%-36.7%) in those who were on ART for ≤6 months based on harmonization criteria for the Asian population; the confidence intervals overlapped and apparently observed difference was not statistically significant. Adjusted for age, body mass index (BMI), protease inhibitor (PI)-based ART regimen, duration of ART, insulin resistance (IR), reported family history of hypertension and residential setting, factors independently associated with MetS were PI containing ART regimen, IR, duration of ART intake and BMI. In the adjusted model, the odds of MetS were three times higher among PLH on PI containing ART regimen (95% CI of adjusted odds ratio; aOR 1.27-8.51) and those having IR (95% CI of aOR 1.48-5.07). The odds of MetS among PLH with BMI ≥23 kg/m2 was 4 (95% CI of aOR 2.08-6.81) times higher than those with lower BMI. Conclusions: MetS in PLH requires the attention of health-care workers in India. Appropriate screening would help initiate early management.

Seroprevalence of Anti-SARS-CoV-2 IgG Antibodies among HIV Infected Individuals Attending ART Centre at Pune: A Cross-Sectional Study.

Background: We aimed to determine the anti-SARS-CoV-2 IgG antibodies among people living with HIV (PLHIV) in Pune, India. Methods: This cross-sectional study was conducted between March 2021 and June 2021. Demographic and clinical information related to coronavirus disease 2019 (COVID-19) were recorded on structured questionnaires. Blood samples were collected and tested for anti-SARS-CoV-2 IgG antibodies using commercial ELISA. Results: Of the 405 HIV infected individuals enrolled in the study, 223(55.1%) were females. Mean age and CD4 count of participants were 42 years (SD: 10) and 626 cells/mm3 (SD: 284) respectively. A total of 382 (95%) PLHIV were virologically suppressed. The seropositivity against SARS-CoV-2 was found in 221 PLHIV (54.6%, 95% CI: 49.7-59.4). No significant association was found between demographic or clinical factors and seropositivity. Conclusion: A high prevalence of anti-SARS-CoV-2 IgG antibodies was found among PLHIV attending ART centre indicating an exposure to the virus among them.

Ocular manifestations and refractive errors among people living with HIV in Pune, India: a cross-sectional study.

OBJECTIVE: We aimed to determine the ocular manifestation and refractive error prevalences among people living with HIV (PLHIV) in Pune, India. METHODS: This cross-sectional study included HIV-infected adults attending a National AIDS Research Institute clinic. Ophthalmologic examination included visual acuity estimation, refraction, orthoptic evaluation, slit lamp and fundus examination, and photography. RESULTS: In total, 441 HIV-infected individuals were enrolled. The participants' median age was 44 (interquartile range 38-49) years and 227 (51.5%) were men. Refractive errors occurred in 132 (29.9%) individuals. Ocular manifestations were present in 93 (21.1%) participants and the most frequent was cataract in 59 (13.4%) participants. Multivariate logistic regression analysis showed that participants who were illiterate (adjusted odds ratio [AOR] 2.80, 95% confidence interval [CI] 1.47-5.33) and those aged greater than 40 years (AOR 5.59, 95% CI 2.69-11.61) were more likely to have ocular manifestations. The odds of having ocular manifestations were greater in participants with treatment substitution or changes (AOR 2.11, 95% CI 1.16-3.82). CONCLUSIONS: Cataract and refractive errors were prevalent among PLHIV. PLHIV should be encouraged to have regular ophthalmic checkups. Individuals with lower education levels and older age should be counseled regarding eye care and timely reporting of ocular symptoms.

HIV Skews a Balanced Mtb-Specific Th17 Response in Latent Tuberculosis Subjects to a Pro-inflammatory Profile Independent of Viral Load.

HIV infection predisposes latent tuberculosis-infected (LTBI) subjects to active TB. This study is designed to determine whether HIV infection of LTBI subjects compromises the balanced Mycobacterium tuberculosis (Mtb)-specific T helper 17 (Th17) response of recognized importance in anti-TB immunity. Comparative analysis of Mtb- and cytomegalovirus (CMV)-specific CD4+ T cell responses demonstrates a marked dampening of the Mtb-specific CD4+ T cell effectors and polyfunctional cells while preserving CMV-specific response. Additionally, HIV skews the Mtb-specific Th17 response in chronic HIV-infected LTBI progressors, but not long-term non-progressors (LTNPs), with preservation of pro-inflammatory interferon (IFN)-γ+/interleukin-17+ (IL-17+) and significant loss of anti-inflammatory IL-10+/IL-17+ effectors that is restored by anti-retroviral therapy (ART). HIV-driven impairment of Mtb-specific response cannot be attributed to preferential infection as cell-associated HIV DNA and HIV RNA reveal equivalent viral burden in CD4+ T cells from different antigen specificities. We therefore propose that beyond HIV-induced loss of Mtb-specific CD4+ T cells, the associated dysregulation of Mtb-specific T cell homeostasis can potentially enhance the onset of TB in LTBI subjects.

Elevated Levels of Galectin-9 but Not Osteopontin in HIV and Tuberculosis Infections Indicate Their Roles in Detecting MTB Infection in HIV Infected Individuals.

Galectin-9 (Gal-9) and osteopontin (OPN) play immunomodulatory roles in tuberculosis and HIV infections. Evaluation of their levels as well as their interplay with different pro-inflammatory cytokines is critical to understand their role in immunopathogenesis of HIV/tuberculosis co-infection considering the complexity of the disease. Plasma levels of these proteins were measured by ELISAs in HIV-negative individuals with pulmonary (n = 21), extrapulmonary (n = 33), and latent tuberculosis (n = 22) and in HIV infected patients with pulmonary (n = 14), latent tuberculosis (n = 17), and without tuberculosis (n = 41). Levels of pro-inflammatory cytokines were estimated by Luminex assay. Receiver operated characteristic curve analysis was performed to evaluate discriminatory roles of these proteins. Spearman's correlation analysis was performed with the markers of HIV and tuberculosis disease progression to evaluate their immunopathogenic roles. Gal-9 and OPN levels were higher in HIV uninfected patients with active tuberculosis than with latent tuberculosis. Gal-9 but not OPN levels were higher in HIV infected patients with active tuberculosis than with latent tuberculosis. Area under curve for Galectin-9 was >0.9 in HIV/tuberculosis co-infection and extrapulmonary tuberculosis. OPN and IL-6 levels were higher in patients with severe chest X-ray grade indicating its association with severity of the disease and positively correlated with each other. Stronger positive and negative correlations of Gal-9 levels, respectively, with viral loads and CD4 cell counts in HIV infected patients were observed than OPN levels indicating their association with HIV disease progression. Thus, significantly elevated Gal-9 levels were reported for the first time in HIV/tuberculosis co-infection and extrapulmonary tuberculosis in our study than single infections with HIV and tuberculosis. The study indicated a need for further evaluation of monitoring role of Gal-9 for detection of developing tuberculosis in HIV infected individuals. The findings also indicated differential roles of Gal-9 and OPN in the pathogenesis of tuberculosis and HIV infections.

Higher frequencies of functional HIV-envelope-specific memory B cells are associated with nonprogressive HIV infection in Indian population.

OBJECTIVE: The HIV-1-specific antibodies are being considered for prevention and therapy in HIV infection. For effective antibody response, presence of functionally competent memory B cells (MEBs) is important; however, HIV-infection is known to alter the B-cell functionality. Very limited data are available on the HIV-specific memory B-cell population in HIV-infected Indian population. METHODS: In this study, the frequencies of HIV-gp140-specific MEBs were measured in individuals with nonprogressive [long-term-nonprogressors (LTNPs), N = 20] and progressive (N = 19) HIV infection using multicolor flow cytometry. The activation and functional status of these MEBs were assessed as frequencies and mean fluorescence intensity (MFI) of the CD38 and CD40 expression, respectively. RESULTS: The percentages of gp140 + MEBs were higher in LTNPs than seen in progressors (P = 0.0475) and associated with higher CD4 cell count (P = 0.0312, r = 0.2833). As compared with the progressors, LTNPs also showed higher functional (CD40+) gp140 + MEBs both frequencies (P < 0.0001) and CD40 MFI (P = 0.0222), whereas the frequencies (<0.0001) and the MFI (P = 0.0047) of CD38 expression was significantly lower. Higher CD4 cell counts and lower plasma viral load values were associated with higher frequencies of CD40+ gp140 + MEBs (P < 0.0001, r = 0.4962) (P = 0.0036, r = -0.4202) and lower frequencies (P = 0.0008, r = -0.4231) and CD38 expression (MFI) (P = 0.004, r = -0.3719) (P = 0.0066, r = 0.4033). CONCLUSION: Our study suggests that LTNPs have functional HIV-specific memory B-cell compartment with reduced activation that may lead to effective HIV-specific humoral immune responses contributing to their nondisease progression status. These findings would help in better understanding of the characteristics of the HIV-specific memory B-cell population in nonprogressive HIV infection.

Possible role of plasma Galectin-9 levels as a surrogate marker of viremia in HIV infected patients on antiretroviral therapy in resource-limited settings.

BACKGROUND: Early detection of viremia in HIV infected patients on anti-retroviral therapy (ART) is important to prevent disease progression as well as accumulation of drug resistance mutations. This makes HIV viral load (VL) monitoring indispensable in HIV infected patients on ART. However VL, being an expensive test, results in heavy financial burden on health services. Hence, cheaper surrogate markers of viremia are desired to reduce overall cost of management of HIV infected patients. METHODS: We enrolled aviremic (n = 63, M:F = 31:32) and viremic (n = 43, M:F = 21:22) HIV infected patients at 1 year after ART initiation. Viremic individuals were identified as those having a plasma VL of more than 1000 copies/µl and aviremic individuals as less than 40 copies/µl. The study participants also included immuno-virologically discordant patients as they demonstrate differential degrees of immune-reconstitution and are likely to harbour concomitant infections influencing levels of immune-activation markers screened as the surrogate markers. Immune activation markers viz. plasma hs-CRP, soluble-CD14 and Galectin-9 levels were estimated by ELISA, IL-6 by luminex assay and percentages of CD38+ CD8+ cells were determined by flow cytometry. The levels were compared between viremic and aviremic patients and correlated with plasma viral load. Receiver operated curve (ROC) analysis was done for plasma Galectin-9 levels. RESULTS: Viremic patients had significantly higher levels of Galectin-9 and %CD38+ CD8+ cells (p values < 0.0001) than aviremic patients. Levels of the other activation markers did not differ between viremic and aviremic individuals. Galectin-9 levels (r = 0.76) and %CD38+ CD8+ cells (r = 0.39) correlated positively with VL. Area under curve for Galectin-9 levels for distinguishing between viremic and aviremic individuals was 0.98. Youden index, sensitivity, specificity, positive predictive value and negative predictive value for Galectin-9 levels were 0.87, 0.97, 0.90, 0.87 and 0.98, respectively, at the cut-off value of 5.79 ng/ml. CONCLUSIONS: Plasma Galectin-9 levels could identify viremic individuals with sensitivity and specificity of more than 90%. Thus, they showed a potential to serve as a surrogate marker of viremia in HIV infected patients on ART and would have cost implications on HIV management especially in resource-limited settings. However, the findings need to be confirmed in the patients on ART for different durations of time.

High IL-5 levels possibly contributing to HIV viremia in virologic non-responders at one year after initiation of anti-retroviral therapy.

Lack of viral monitoring in HIV infected patients on anti-retroviral therapy in low income countries may result in missing virologic non-responders (VNR) who show immunologic recovery in spite of unsuppressed viral replication. Biomarkers and drug resistance patterns in these discordant patients in comparison to the concordant treatment failure group need to be studied to understand possible risk factors associated with this condition. HIV infected patients on anti-retroviral therapy for one year were enrolled under three categories namely VNRs (n = 25), treatment failures (n = 18) and treatment responders (n = 40). They were assessed for HIV drug resistance by sequencing, plasma cytokines by luminex assay, T cell activation status by flow cytometry and total IgE levels by ELISA. VNR and failure patients had significantly lower median baseline CD4 counts than the responders. VNRs had significantly higher CD4 counts but lower viral load than treatment failures at one year of ART. VNRs had the highest eosinophil counts and the highest IL-5 levels among all the groups. IL-5 levels in them correlated with their viral load values. Frequency of Treg cells was also highest among the VNR group participants. More than 60% of the viremic patients irrespective of their groups harboured multiple HIV drug resistance mutations and mutation pattern did not differ between the groups. Low baseline CD4 counts and presence of multiple drug resistance mutations in the viremic groups highlighted the importance of early ART initiation and viral load monitoring irrespective of presence of immunologic failure. High IL-5 levels in VNR group indicated a need for investigating causal relationship between IL-5 and viral replication to devise therapeutic strategies to control viremia.

Higher Baseline ADCC Responses in Chronic Nonprogressive HIV Infection Are Associated with Reduced HIV Burden in Later Course of Disease.

The importance of anti-HIV antibodies mediating antibody-dependent cell-mediated cytotoxicity (ADCC) in protective immunity against HIV is recognized recently. The purpose of this study was to measure the functional ADCC response at different stages of HIV infection in a well-defined HIV+ cohort, including 20 recently infected individuals, 30 with long-term slow-progressive, 24 with short-term slow-progressive and 32 with progressive HIV infection using a rapid fluorometric ADCC assay. The antibodies mediating ADCC were found in all disease stages. These antibodies were detectable at as early as 25 days after the estimated date of infection, however, did not influence the viral load set point probably indicating no major influence on the early course of the disease. However, the frequency and magnitude of functional ADCC responses were associated with higher CD4+T cell count and lower viral load and were significantly lower in progressors compared with other groups. The usefulness of the ADCC responses in longer viral control was assessed in a subset of participants with slowly progressing HIV infection. In these individuals, the ADCC responses observed at the visit 1 were found to be increased over time and were associated with lower plasma viral load estimated 4 to 15 years later in the disease course. Overall, the study findings confirm the role of ADCC antibodies in reducing the viral burden and also indicate the probable role of sustained functional ADCC responses in reducing the viral burden during the later period of HIV infection.

Short Communication: Nonprogressive HIV-1 Infection Is Associated with Expansion of IL-21R Expressing Class-Switched Memory B Cells.

HIV perturbs the functionality of B cells resulting in defective humoral responses. As efficient humoral immune responses are important in controlling HIV-disease progression, we characterized the memory B cell population for its subsets and their activation (CD38 expression) and functional [interleukin (IL)-21R expression] profile in individuals with nonprogressive [long-term nonprogressors (LTNPs), N = 16] and progressive HIV disease (progressors, N = 16) along with 10 HIV uninfected healthy controls (HCs). The frequencies of total memory B cells were similar in HCs and HIV-infected individuals, whereas the frequencies of unswitched memory B (UMB) cells and CD38+ UMB cells were significantly higher in progressors than LTNPs and HCs (p < .03). LTNPs showed higher frequencies of class-switched memory B (SMB) cells and IL-21R expressing SMB cells than seen in progressors (p = .019), which were similar to that seen in HCs. The %UMB cells correlated inversely (p = .0002, r = -0.6053) and %SMB cells correlated positively (p = .0005, r = 0.5804) with CD4 count. IL-21/IL-21R interaction is required for class switching of B cells and differentiation into antibody-secreting plasma cells. The higher expression of IL-21R on class SMB cells from LTNPs might be resulting in efficient plasma cell differentiation and the functional humoral immune response that might be responsible for mounting efficient antibody response against the encountered infections. The more insights in this area might be required to further understand the role of IL-21R expressing class SMB cells in HIV infection.

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.

How reliable and valid are the self-reports of sexual behavior among HIV discordant couples in Pune, INDIA.

Reliability of self-reported sexual and safe sex behavior among heterosexual HIV discordant couples was assessed by matching individual responses of couples to a common set of questions and validated by matching with pregnancy and seroconversion during study period. Demographic, clinical and sexual behavior information was collected individually from 457 consenting married discordant couples using structured questionnaires at screening, enrollment and at four quarterly visits. Reliability of self-reports tested using Kappa statistics. At screening, level of agreement about spouse being regular partner (Kappa = 0.96) and having had sexual intercourse with spouse in the last quarter (Kappa = 0.84) was noted. Moderate agreement observed about frequency of condom use (Kappa = 0.639) and condom tear (Kappa = 0.428). Agreement on reporting sexual contacts with spouse and consistent condom use increased (P < 0.001) over follow-ups. Four of 6 couples that seroconverted reported using condoms consistently, and 2 of these seroconverted. Couple histories of all 11 sero-discordant couples reporting pregnancy matched, of these 8 couples reported use of condoms and only 3 couples reported non-use of condoms during the preceding period. Sensitive sexual information can be collected using self-reports but it should be used with caution. Involving couples and using biological parameters concurrently may enhance validity of self-reports.

Brief Report: The Anti-HIV-1 ADCC-Mediating Antibodies From Cervicovaginal Secretions of HIV-Infected Women Have an Ability to Mediate Lysing of Autologous CD4+ HIV-Infected Cells.

BACKGROUND: Fragment crystallizable region of antibody-mediated mechanism such as antibody-dependent cellular cytotoxicity (ADCC) has been identified as an important component of immune protection against HIV. We assessed whether the anti-HIV antibodies mediating ADCC from cervicovaginal lavages (CVLs) of HIV-infected women have an ability to mediate lysing of autologous CD4 HIV-infected cells. METHODOLOGY: The CVLs of 62 HIV-infected (37 long-term slow progressors and 25 with progressive HIV infection: progressors) and 20 HIV-uninfected Indian women with high risk of HIV acquisition were tested for the presence of ADCC-mediating anti-HIV antibodies against HIV-1 C Env in a fluorometric assay. Furthermore, we tested the ability of these antibodies to mediate ADCC-dependent killing of the autologous HIV-infected CD4 T cells using paired peripheral blood mononuclear cells containing target and effector cells. RESULTS: The numbers of ADCC responders were significantly higher in long-term slow progressors (34/37) as compared to the progressor group (9/25) with no significant difference in the magnitude. The magnitude of response was inversely associated with detectable CVL viral load (P < 0.003). The lysis of target cells was significantly higher in enriched IgG fraction as compared to the respective non-IgG fraction. The ADCC antibodies from CVLs significantly reduced the frequency of HIV-1 Env-activated autologous CD4 T cells in the presence of autologous effector cells. CONCLUSIONS: The presence of ADCC antibodies in CVLs with an ability to mediate lysing of HIV-infected autologous CD4 T cells provides evidence of their promising contribution to mucosal defense against HIV-1 and has implications in designing prophylactic and immunotherapeutic strategies.