Search

Background: Human immunodeficiency virus (HIV)–infected pregnant women increasingly receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggest HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but most evidence relates to the pre-ART era, breastfeeding of limited duration, and considerable maternal mortality. Maternal ART and prolonged breastfeeding while on ART may improve survival, although this has not been reliably quantified. Methods: Individual data on 19 219 HEU children from 21 PMTCT trials/cohorts undertaken from 1995 to 2015 in Africa and Asia were pooled to estimate the association between 24-month mortality and maternal/infant factors, using random-effects Cox proportional hazards models. Adjusted attributable fractions of risks computed using the predict function in the R package “frailtypack” were used to estimate the relative contribution of risk factors to overall mortality. Results: Cumulative incidence of death was 5.5% (95% confidence interval, 5.1–5.9) by age 24 months. Low birth weight (LBW <2500 g, adjusted hazard ratio (aHR, 2.9), no breastfeeding (aHR, 2.5), and maternal death (aHR, 11.1) were significantly associated with increased mortality. Maternal ART (aHR, 0.5) was significantly associated with lower mortality. At the population level, LBW accounted for 16.2% of 24-month mortality, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; combined, these factors explained 63.6% of deaths by age 24 months. Conclusions: Survival of HEU children could be substantially improved if public health practices provided all HIV-infected mothers with ART and supported optimal infant feeding and care for LBW neonates.

Background: Prior observation has shown differences in COVID-19 hospitalization risk between SARS-CoV-2 variants, but limited information describes hospitalization outcomes., Methods: Inpatients with COVID-19 at 5 hospitals in the eastern United States were included if they had hypoxia, tachypnea, tachycardia, or fever, and SARS-CoV-2 variant data, determined from whole-genome sequencing or local surveillance inference. Analyses were stratified by history of SARS-CoV-2 vaccination or infection. The average effect of SARS-CoV-2 variant on 28-day risk of severe disease, defined by advanced respiratory support needs, or death was evaluated using models weighted on propensity scores derived from baseline clinical features., Results: Severe disease or death within 28 days occurred for 977 (29%) of 3369 unvaccinated patients and 269 (22%) of 1230 patients with history of vaccination or prior SARS-CoV-2 infection. Among unvaccinated patients, the relative risk of severe disease or death for Delta variant compared with ancestral lineages was 1.30 (95% confidence interval [CI]: 1.11-1.49). Compared with Delta, the risk for Omicron patients was .72 (95% CI: .59-.88) and compared with ancestral lineages was .94 (.78-1.1). Among Omicron and Delta infections, patients with history of vaccination or prior SARS-CoV-2 infection had half the risk of severe disease or death (adjusted hazard ratio: .40; 95% CI: .30-.54), but no significant outcome difference by variant., Conclusions: Although risk of severe disease or death for unvaccinated inpatients with Omicron was lower than with Delta, it was similar to ancestral lineages. Severe outcomes were less common in vaccinated inpatients, with no difference between Delta and Omicron infections., Competing Interests: Potential conflicts of interest. The Maryland Department of Health collaborates for research with BioRad, Hologic, and DiaSorin. J. B. has equity/entitlement to future royalties in miDiagnostics. B. T. G. is a member of the Food and Drug Administration (FDA) Pulmonary-Asthma Drug Advisory Committee and a board member of the Society of Bedside Medicine and has received consulting fees from Janssen Research and Development, LLC (related to vaccine trial case adjudication); Gilead Sciences, Inc (related to COVID therapeutics); and Atea Pharmaceuticals, Inc (related to COVID therapeutics). R. B. is a consultant for Merck & Co and Hologic. R. B. also reports royalties or licenses from emocha Health, support for attending meetings and/or travel from Hologic, and participation on a Data Safety Monitoring Board or Advisory Board for Merck. H. H. M. reports the following grants or contracts unrelated to this work: National Institutes of Health (NIH) UM1AI0686, NIH UM1 AI068613-14, NIH R01 DA045556-04S1, NIH 3U54HL143541-02S2, NIH 4UH3CA211396-03, and NIH R01 CA243393 and receipt of equipment, materials, drugs, medical writing, gifts, or other services related to research contract from BioRad, DiaSorin, and Hologic. D. C. G. reports grants or contracts unrelated to this work from Illumina, Inc; IDbyNDA, Inc; and Fisher Center Discovery Program, Johns Hopkins; consulting fees from bioMerieux, Inc; and payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from the American Association of Clinical Chemistry and Pan American Society of Clinical Virology. A. G. reports unrelated grants or contracts from NIH and Unitaid and the Centers for Disease Control and Prevention (CDC); participation on an NIH/NIAID Advisory Council and Indo US Science Technology Governing Board; and roles on the IMPAACT Network TB Scientific Committee and World Health Organization (WHO) MDR TB Guidelines Committee. M. L. R. reports grants or contracts unrelated to this work from Critical Path Institute/FDA, paid to their institution. S. L. Z. reports the following grants or contracts unrelated to this work: 1R01AR073208-01 (Shah) (1 April 2018–31 March 2023), NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Autoantibodies Define Scleroderma Subgroups with Distinct Relationships to Cancer; UL1TR003098 (Ford) (1 June 2019–30 April 2024), NIH/National Center for Advancing Translational Sciences (NCATS), Johns Hopkins Institutional Clinical and Translational Science Award. S. L. Z. also reports a role as Co-Director for Data Science, JHM inHealth Precision Medicine (paid to their institution). These conflicts of interest are being managed by the Johns Hopkins University in accordance with its conflict-of-interest policies. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Development of and increased access to generic oral medications to treat high-burden diseases including human immunodeficiency virus (HIV), tuberculosis, viral hepatitis, and malaria have had a major impact on reducing global morbidity and mortality. However, access and adherence to these life-saving treatments remains limited for some of the most vulnerable and underserved populations, for whom stigma, control, and discretion are critical to decisions around care. Current efforts to develop long-acting formulations to treat and prevent these conditions could overcome many of these barriers. However, generic manufacturing of these innovative products will be required to ensure affordable access to the communities and patients in greatest need. Strategic investments in new infrastructure will be required even before markets and manufacturing costs are clear, to ensure that access to these new products is not delayed, particularly for patients in low- and middle-income countries. Unlike conventional oral medications, long-acting products require greater investment for formulation, packaging, and delivery. The requirement for long-term bioequivalence studies will introduce additional delays in regulatory approval of generic long-acting products, and expedited approval pathways must be developed. Lessons learned from the development of long-acting hormonal contraceptives and long-acting antiretroviral products may provide a way forward., Competing Interests: Potential conflicts of interest. C. F. reports serving as a paid consultant for Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories, and ViiV Healthcare, and chairs the Scientific Advisory Board for Navigen Corporation. He is also the co-inventor on 2 issued patents related to the development of long-acting formulations for delivery of antiretroviral drugs. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There is an urgent need to understand the real-world effectiveness of remdesivir in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: This was a retrospective comparative effectiveness study. Individuals hospitalized in a large private healthcare network in the United States from 23 February 2020 through 11 February 2021 with a positive test for SARS-CoV-2 and ICD-10 diagnosis codes consistent with symptomatic coronavirus disease 2019 (COVID-19) were included. Remdesivir recipients were matched to controls using time-dependent propensity scores. The primary outcome was time to improvement with a secondary outcome of time to death., Results: Of 96 859 COVID-19 patients, 42 473 (43.9%) received at least 1 remdesivir dose. The median age of remdesivir recipients was 65 years, 23 701 (55.8%) were male, and 22 819 (53.7%) were non-White. Matches were found for 18 328 patients (43.2%). Remdesivir recipients were significantly more likely to achieve clinical improvement by 28 days (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI], 1.16-1.22). Remdesivir patients on no oxygen (aHR 1.30, 95% CI, 1.22-1.38) or low-flow oxygen (aHR 1.23, 95% CI, 1.19-1.27) were significantly more likely to achieve clinical improvement by 28 days. There was no significant impact on the likelihood of mortality overall (aHR 1.02, 95% CI, .97-1.08). Remdesivir recipients on low-flow oxygen were significantly less likely to die than controls (aHR 0.85, 95% CI, .77-.92; 28-day mortality 8.4% [865 deaths] for remdesivir patients, 12.5% [1334 deaths] for controls)., Conclusions: These results support the use of remdesivir for hospitalized COVID-19 patients on no or low-flow oxygen. Routine initiation of remdesivir in more severely ill patients is unlikely to be beneficial., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Rapid tests have transformed the landscape of available tools for clinicians caring for patients who are critically ill. Their emergence as part of routine care increases the capacity for similar devices to reverse or minimize major epidemics and assist healthcare providers in their clinical decision-making. To assess how a point-of-care complete blood count (CBC) could change patterns in clinical decision-making, we presented low and middle income (LMIC) healthcare providers with hypothetical clinical scenarios to understand how such a device could impact the way they treat and refer patients., Methods: Our survey asked about current use of CBC results, and then presented three separate scenarios that occur in LMICs. Survey respondents were queried about how they might change hospitalization plans and/or mediations based on point-of-care CBC results., Results: In all three scenarios, a majority of clinicians were likely to modify the way they triage patients based on real-time results., Conclusion: Our survey demonstrates that a point-of-care CBC diagnostic could change the way providers in resource-limited settings treat and refer critically ill patients. All hypothetical clinical scenarios describe common, urgent case presentations that can occur at any level of a health system in resource-limited settings. Rapid, simple and accessible technology for basic lab tests like CBC could impact patient care in low and middle-income countries by providing health care workers with actionable data with the potential to affect patient-centered outcomes., (© 2018 American Association for Clinical Chemistry.)

Background: Preterm birth (PTB) rates are high in human immunodeficiency virus (HIV)-infected populations, even when on treatment. Still, only a subset of all births in HIV-infected pregnant women result in PTB, suggesting that risk factors other than HIV infection itself are also important. Inflammation is a known risk factor in uninfected populations, but its role in HIV-infected population have not been studied; in addition, the immune pathways involved are not clear and noninvasive immune markers with predictive value are lacking. Our objective was to determine the association of select markers of inflammation with PTB in HIV-1-infected pregnant women., Methods: Within a randomized trial of pregnant women receiving nevirapine (Six-Week Extended-Dose Nevirapine [SWEN] trial), we nested a case-control study (n = 107; 26 cases, 81 controls) to determine the association of maternal inflammation with PTB. Cases were defined as PTB (<37 weeks' gestational age). We assessed inflammation by measuring plasma levels of markers of general inflammation (C-reactive protein [CRP]), intestinal barrier dysfunction (intestinal fatty acid binding protein [I-FABP]), and microbial translocation/monocyte activation (soluble CD14 [sCD14] and CD163 [sCD163]). Multivariable logistic regression was used to determine the odds of PTB per log2 increase of each marker., Results: In multivariable models, there was increased odds of PTB per unit increase of log2 sCD14 (adjusted odds ratio [aOR], 2.45; 95% confidence interval [CI], 1.24-4.86), log2 sCD163 (aOR, 3.87; 95% CI, 1.43-10.49), and log2 I-FABP (aOR, 2.28; 95% CI, 1.18-4.41) but not log2 CRP (aOR, 0.72; 95% CI, .48-1.09)., Conclusions: Our results show that select immune markers can identify women at higher risk for PTB in HIV-1-infected populations and suggest that modulating gut barrier integrity and microbial translocation may affect PTB., Clinical Trials Registration: NCT00061321.

Background: Both wasting and obesity are associated with inflammation, but the extent to which body weight changes influence inflammation during human immunodeficiency virus infection is unknown., Methods: Among a random virologically suppressed participants of the Prospective Evaluation of Antiretrovirals in Resource-Limited Settings trial, inflammatory markers were measured at weeks 0, 24, and 48 after antiretroviral therapy (ART) initiation. Associations between both baseline and change in body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared) and changes in inflammation markers were assessed using random effects models., Results: Of 246 participants, 27% were overweight/obese (BMI, ≥ 25), and 8% were underweight (BMI < 18.5) at baseline. After 48 weeks, 37% were overweight/obese, and 3% were underweight. While level of many inflammatory markers decreased 48 weeks after ART initiation in the overall group, the decrease in C-reactive protein (CRP) level was smaller in overweight/obese participants (P = .01), and the decreases in both CRP (P = .01) and interleukin 18 (P = .02) levels were smaller in underweight participants. Each 1-unit gain in BMI among overweight/obese participants was associated with a 0.02-log10 increase in soluble CD14 level (P = .05), while each 1-unit BMI gain among underweight participants was associated with a 9.32-mg/L decrease in CRP level (P = .001)., Conclusions: Being either overweight or underweight at ART initiation was associated with heightened systemic inflammation. While weight gain among overweight/obese persons predicted increased inflammation, weight gain among underweight persons predicted reduced inflammation., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

A case-cohort analysis of human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART) was performed within a multicountry randomized trial (PEARLS) to assess the prevalence of persistently elevated C-reactive protein (CRP) levels, based on serial measurements of CRP levels, and their association with HIV clinical failure. A persistently elevated CRP level in plasma (defined as ≥ 5 mg/L at both baseline and 24 weeks after ART initiation) was observed in 50 of 205 individuals (24%). A persistently elevated CRP level but not an elevated CRP level only at a single time point was independently associated with increased clinical failure, compared with a persistently low CRP level, despite achievement of virologic suppression. Serial monitoring of CRP levels could identify individuals who are at highest risk of HIV progression and may benefit from future adjunct antiinflammatory therapies., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Elevated soluble CD14 (sCD14) concentrations, a marker of monocyte activation, predicts adverse outcomes in human immunodeficiency virus (HIV)-infected adults. To examine the association of sCD14 concentrations with the risk of mother-to-child transmission (MTCT) of HIV, we nested a case-control study (49 pairs of infants and their HIV-infected mothers) within the Six-Week Extended-Dose Nevirapine trial. Median peripartum maternal log2 sCD14 concentration was higher among transmitters (defined as pairs in which maternally transmitted HIV infection occurred by 12 months of age) than nontransmitters (20.29 pg/mL vs 19.41 pg/mL; P = .005). There was an increased odds of MTCT for every log2 increase in maternal sCD14 concentration, after adjustment for maternal HIV load, CD4 count and cART exposure (adjusted odds ratio, 3.51; 95% confidence interval, 1.21-10.21). Maternal monocyte activation may adversely influence the risk of MTCT of HIV., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Anemia is a known risk factor for clinical failure following antiretroviral therapy (ART). Notably, anemia and inflammation are interrelated, and recent studies have associated elevated C-reactive protein (CRP), an inflammation marker, with adverse human immunodeficiency virus (HIV) treatment outcomes, yet their joint effect is not known. The objective of this study was to assess prevalence and risk factors of anemia in HIV infection and to determine whether anemia and elevated CRP jointly predict clinical failure post-ART., Methods: A case-cohort study (N = 470 [236 cases, 234 controls]) was nested within a multinational randomized trial of ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings [PEARLS]). Cases were incident World Health Organization stage 3, 4, or death by 96 weeks of ART treatment (clinical failure). Multivariable logistic regression was used to determine risk factors for pre-ART (baseline) anemia (females: hemoglobin <12.0 g/dL; males: hemoglobin <13.0 g/dL). Association of anemia as well as concurrent baseline anemia and inflammation (CRP ≥ 10 mg/L) with clinical failure were assessed using multivariable Cox models., Results: Baseline anemia prevalence was 51% with 15% prevalence of concurrent anemia and inflammation. In analysis of clinical failure, multivariate-adjusted hazard ratios were 6.41 (95% confidence interval [CI], 2.82-14.57) for concurrent anemia and inflammation, 0.77 (95% CI, .37-1.58) for anemia without inflammation, and 0.45 (95% CI, .11-1.80) for inflammation without anemia compared to those without anemia and inflammation., Conclusions: ART-naive, HIV-infected individuals with concurrent anemia and inflammation are at particularly high risk of failing treatment, and understanding the pathogenesis could lead to new interventions. Reducing inflammation and anemia will likely improve HIV disease outcomes. Alternatively, concurrent anemia and inflammation could represent individuals with occult opportunistic infections in need of additional screening., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Low 25-hydroxyvitamin D (25(OH)D) has been associated with increased HIV mortality, but prospective studies assessing treatment outcomes after combination antiretroviral therapy (cART) initiation in resource-limited settings are lacking., Methods: A case-cohort study (N = 411) was nested within a randomized cART trial of 1571 cART-naive adults in 8 resource-limited settings and the United States. The primary outcome (WHO stage 3/4 disease or death within 96 weeks of cART initiation) was met by 192 cases, and 152 and 29 cases met secondary outcomes of virologic and immunologic failure. We studied prevalence and risk factors for baseline low 25(OH)D (<32 ng/mL) and examined associated outcomes using proportional hazard models., Results: Low 25(OH)D prevalence was 49% and ranged from 27% in Brazil to 78% in Thailand. Low 25(OH)D was associated with high body mass index (BMI), winter/spring season, country-race group, and lower viral load. Baseline low 25(OH)D was associated with increased risk of human immunodeficiency virus (HIV) progression and death (adjusted hazard ratio (aHR) 2.13; 95% confidence interval [CI], 1.09-4.18) and virologic failure (aHR 2.42; 95% CI, 1.33-4.41)., Conclusions: Low 25(OH)D is common in diverse HIV-infected populations and is an independent risk factor for clinical and virologic failure. Studies examining the potential benefit of vitamin D supplementation among HIV patients initiating cART are warranted., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Optimum comprehension of informed consent by research participants is essential yet challenging. This study explored correlates of lower comprehension of informed consent among 1334 participants of a cohort study aimed at estimating HIV incidence in Pune, India., Methods: As part of the informed consent process, a structured comprehension tool was administered to study participants. Participants scoring ≥90% were categorised into the 'optimal comprehension group', whilst those scoring 80-89% were categorised into the 'lower comprehension group'. Data were analysed to identify sociodemographic and behavioural correlates of lower consent comprehension., Results: The mean ± SD comprehension score was 94.4 ± 5.00%. Information pertaining to study-related risks was not comprehended by 61.7% of participants. HIV-negative men (adjusted OR [AOR] = 4.36, 95% CI 1.71-11.05) or HIV-negative women (AOR = 13.54, 95% CI 6.42-28.55), illiteracy (AOR= 1.65, 95% CI 1.19-2.30), those with a history of multiple partners (AOR = 1.73, 95% CI 1.12-2.66) and those never using condoms (AOR = 1.35, 95% CI 1.01-1.82) were more likely to have lower consent comprehension., Conclusions: We recommend exploration of domains of lower consent comprehension using a validated consent comprehension tool. Improved education in these specific domains would optimise consent comprehension among research participants.

Background: In resource-limited settings, mothers infected with human immunodeficiency virus type 1 (HIV-1) face a difficult choice: breastfeed their infants but risk transmitting HIV-1 or not breastfeed their infants and risk the infants dying of other infectious diseases or malnutrition. Recent results from observational studies and randomized clinical trials indicate daily administration of nevirapine to the infant can prevent breast-milk HIV-1 transmission., Methods: Data from 5396 mother-infant pairs who participated in 5 randomized trials where the infant was HIV-1 negative at birth were pooled to estimate the efficacy of infant nevirapine prophylaxis to prevent breast-milk HIV-1 transmission. Four daily regimens were compared: nevirapine for 6 weeks, 14 weeks, or 28 weeks, or nevirapine plus zidovudine for 14 weeks., Results: The estimated 28-week risk of HIV-1 transmission was 5.8% (95% confidence interval [CI], 4.3%-7.9%) for the 6-week nevirapine regimen, 3.7% (95% CI, 2.5%-5.4%) for the 14-week nevirapine regimen, 4.8% (95% CI, 3.5%-6.7%) for the 14-week nevirapine plus zidovudine regimen, and 1.8% (95% CI, 1.0%-3.1%) for the 28-week nevirapine regimen (log-rank test for trend, P < .001). Cox regression models with nevirapine as a time-varying covariate, stratified by trial site and adjusted for maternal CD4 cell count and infant birth weight, indicated that nevirapine reduces the rate of HIV-1 infection by 71% (95% CI, 58%-80%; P < .001) and reduces the rate of HIV infection or death by 58% (95% CI, 45%-69%; P < .001)., Conclusions: Extended prophylaxis with nevirapine or with nevirapine and zidovudine significantly reduces postnatal HIV-1 infection. Longer duration of prophylaxis results in a greater reduction in the risk of infection.

We evaluated tuberculosis (TB) screening among 799 human immunodeficiency virus (HIV)-infected pregnant women in India. Eleven (1.4%) had active TB. The negative predictive value of screening using cough, fever, night sweats, or weight loss was 99.3%. Tuberculin skin test and targeted chest radiography provided no substantial benefit. TB symptom screening, as recommended by the World Health Organization, is effective for ruling out TB in HIV-infected pregnant women.

Background: Maternal human immunodeficiency virus (HIV) RNA load, CD4 cell count, breast-feeding, antiretroviral use, and malaria are well-established factors associated with mother-to-child transmission (MTCT) of HIV; the role of maternal tuberculosis (TB), however, has not been well established., Methods: The study population was 783 HIV-infected Indian mother-infant pair participants in randomized and ancillary HIV-infected cohorts of the Six Week Extended-Dose Nevirapine (SWEN) Study, a study comparing extended nevirapine versus single-dose nevirapine, to reduce MTCT of HIV among breast-fed infants. Using multivariable logistic regression, we assessed the impact of maternal TB occurring during pregnancy and through 12 months after delivery on risk of MTCT., Results: Of 783 mothers, 3 had prevalent TB and 30 had incident TB at 12 months after delivery. Of 33 mothers with TB, 10 (30%) transmitted HIV to their infants in comparison with 87 of 750 mothers without TB (12%; odds ratio [OR], 3.31; 95% confidence interval [CI], 1.53-7.29; P = .02). In multivariable analysis, maternal TB was associated with 2.51-fold (95% CI, 1.05-6.02; P = .04) increased odds of HIV transmission adjusting for maternal factors (viral load, CD4 cell count, and antiretroviral therapy) and infant factors (breast-feeding duration, infant nevirapine administration, gestational age, and birth weight) associated with MTCT of HIV., Conclusions: Maternal TB is associated with increased MTCT of HIV. Prevention of TB among HIV-infected mothers should be a high priority for communities with significant HIV/TB burden.

Background: In contrast with many other countries, isoniazid preventative therapy is not recommended in clinical care guidelines for human immunodeficiency virus (HIV)-infected persons with latent tuberculosis (TB) in India., Methods: Seven hundred fifteen HIV-infected mothers and their infants were prospectively followed up for 1 year after delivery at a public hospital in Pune, India. Women were evaluated for active TB during regular clinic visits, and tuberculin skin tests were performed. World Health Organization definitions for confirmed, probable, and presumed TB were used. Poisson regression was performed to determine correlates of incident TB, and adjusted probabilities of mortality were calculated., Results: Twenty-four of 715 HIV-infected women who were followed up for 480 postpartum person-years developed TB, yielding a TB incidence of 5.0 cases per 100 person-years (95% confidence interval [CI], 3.2-7.4 cases per 100 person-years). Predictors of incident TB included a baseline CD4 cell count <200 cells/mm(3) (adjusted incident rate ratio [IRR], 7.58; 95% CI, 3.07-18.71), an HIV load >50,000 copies/mL (adjusted IRR, 3.92; 95% CI, 1.69-9.11), and a positive tuberculin skin test result (adjusted IRR, 3.08; 95% CI, 1.27-7.47). Three (12.5%) of 24 women with TB died, compared with 7 (1.0%) of 691 women without TB (IRR, 12.2; 95% CI, 2.03-53.33). Among 23 viable infants with mothers with TB, 2 received a diagnosis of TB. Four infants with mothers with TB died, compared with 28 infants with mothers without TB (IRR, 4.71; 95% CI, 1.19-13.57). Women with incident TB and their infants had a 2.2- and 3.4-fold increased probability of death, respectively, compared with women without active TB and their infants, controlling for factors independently associated with mortality (adjusted IRR, 2.2 [95% CI, 0.6-3.8] and 3.4 [95% CI, 1.22-10.59], respectively)., Conclusions: Among Indian HIV-infected women, we found a high incidence of postpartum TB and associated postpartum maternal and infant death. Active screening and targeted use of isoniazid preventative therapy among HIV-infected women in India should be considered to prevent postpartum maternal TB and associated mother-to-child morbidity and mortality.

Background: Adherence to antiretroviral therapy (ART) and correlates of adherence and virologic suppression among human immunodeficiency virus (HIV)-infected persons receiving ART in private, outpatient clinics in India is unknown., Methods: Between December 2004 and April 2005, persons receiving ART at 3 private clinics in Mumbai, India, were interviewed regarding HIV care and adherence to ART. Physicians also completed a survey for each participant. Quantitative HIV-1 RNA level was determined for 200 participants., Results: Of 279 participants, 73% reported > or = 95% adherence to ART. Adherence was positively associated with age > or = 50 years (adjusted odds ratio [aOR], 3.90), presence of comorbid conditions (aOR, 1.92), medication self-efficacy (aOR, 4.01), absence of pain in the past month (aOR, 2.14), and support from family and friends (aOR, 2.57). Lack of reminders from family members to take medication (aOR, 0.27) was negatively associated with adherence. Of 200 participants, 127 (63.5%) had virologic suppression (RNA level, < 400 copies/mL). Independent correlates of suppression were a regimen containing > or = 3 ART drugs (aOR, 5.52), first ART regimen (aOR, 3.28), adherence to therapy > or = 95% (aOR, 5.70), female sex (aOR, 3.19), and a physical component score > or = 50 (aOR, 1.07)., Conclusion: Self-reported adherence to ART in a sample of patients attending Mumbai's private clinics was relatively high. However, the fact that a detectable viral level was found in nearly 40% of patients suggests that second-line ART regimens, as well as an emphasis on adherence and appropriate ART regimens in India, is needed.

Sex-based differences in the levels of human immunodeficiency virus 1 (HIV-1) RNA in plasma could be associated with differences in the strength of HIV-1-specific CD8(+) T cell responses. CD8(+) effector responses in 18 men and 15 women were measured 0-2 years (time A) and 5-7 years (time B) after seroconversion. CD8(+) effector responses were seen in 7 (39%) of 18 men and 2 (13%) of 15 women at time A (P=.13) and in 12 (67%) of 18 men and 10 (67%) of 15 women at time B (P=.99). At time B, the strength of CD8(+) effector responses correlated with the number of CD4(+) lymphocytes in women ( rho =-0.68; P=.005) but not in men ( rho =-0.14; P=.58). The level of HIV-1 RNA was not associated with the strength of CD8(+) effector responses according to sex, but there was a sex-based difference in the correlation between the strength of CD8(+) effector response and the number of CD4(+) lymphocytes.

To estimate the impact of prevalent and incident herpes simplex virus type 2 (HSV-2) infection on the acquisition of human immunodeficiency virus type 1 (HIV-1), stored serum samples from a cohort of 2732 HIV-1-seronegative patients attending 3 sexually transmitted infection clinics and 1 reproductive tract infection clinic in Pune, India, were screened for HSV-2-specific antibodies. Incident HSV-2 infection was defined serologically as "recent" if a negative result of testing for HSV-2 could be documented within the previous 6 months or "remote" if >6 months had elapsed since the last negative test result. The prevalence of HSV-2 at enrollment was 43%. The HSV-2 incidence was 11.4 cases/100 person-years, and the HIV-1 incidence was 5.8 cases/100 person-years. The adjusted hazard ratios of HIV-1 acquisition from exposure to HSV-2 infection were 1.67 for prevalent HSV-2, 1.92 for remote incident HSV-2, and 3.81 for recent incident HSV-2. Recent incident HSV-2 infection was associated with the highest risk of HIV-1 in this study, which suggests that prevention of HSV-2 infection may reduce the risk of HIV-1 acquisition.

T lymphocyte responses to human immunodeficiency virus (HIV) type 1 Gag were measured in 9 patients by interferon-gamma enzyme-linked immunospot assay at 3 time points within 12 months of infection. Patients with early recognition of HIV-1 Gag had lower subsequent HIV-1 load set points, as measured during the first 2 years of infection, compared with those of patients with undetectable Gag-specific responses (median, 4.27 vs. 5.05 log(10) HIV-1 RNA copies/mL, respectively; P=.028). An inverse correlation existed between the magnitude of the Gag-specific responses and the HIV-1 load set point (r=-0.733; P=.025). Early sustained T lymphocyte responses to HIV-1 Gag may be important for the establishment of virus load set point.