Effectiveness of isoniazid preventive therapy on incidence of tuberculosis among HIV-infected adults in programme setting.

BACKGROUND & OBJECTIVES: As India and other developing countries are scaling up isoniazid preventive therapy (IPT) for people living with HIV (PLHIV) in their national programmes, we studied the feasibility and performance of IPT in terms of treatment adherence, outcome and post-treatment effect when given under programmatic settings. METHODS: A multicentre, prospective pilot study was initiated among adults living with HIV on isoniazid 300 mg with pyridoxine 50 mg after ruling out active tuberculosis (TB). Symptom review and counselling were done monthly during IPT and for six-month post-IPT. The TB incidence rate was calculated and risk factors were identified. RESULTS: Among 4528 adults living with HIV who initiated IPT, 4015 (89%) successfully completed IPT. IPT was terminated in 121 adults (3%) due to grade 2 or above adverse events. Twenty five PLHIVs developed TB while on IPT. The incidence of TB while on IPT was 1.17/100 person-years (p-y) [95% confidence interval (CI) 0.8-1.73] as compared to TB incidence of 2.42/100 p-y (95% CI 1.90-3.10) during the pre-IPT period at these centres (P=0.017). The incidence of TB post-IPT was 0.64/100 p-y (95% CI 0.04-1.12). No single factor was significantly associated with the development of TB. INTERPRETATION & CONCLUSIONS: Under programmatic settings, completion of IPT treatment was high, adverse events minimal with good post-treatment protection. After ruling out TB, IPT should be offered to all PLHIVs, irrespective of their antiretroviral therapy (ART) status. Scaling-up of IPT services including active case finding, periodic counselling on adherence and re-training of ART staff should be prioritized to reduce the TB burden in this community.

The impact of a private-public partnership delivery system on the HIV continuum of care in a South Indian city.

We characterized the impact of a Private-Public Partnership (PPP) on the continuum of HIV care (e.g., treatment initiation, ART effectiveness and loss to follow-up) among adults enrolled at a private hospital/ART link center in the southern state of Karnataka, India from 2007 through 2012. Data on 2326 adults in care were compiled using an electronic database supplemented with medical chart abstraction. Survival methods with staggered entries were used to analyze time to ART initiation and loss to follow-up as well as associated factors. Mixed effects linear regression models were used to assess ART effectiveness. The mean age of adults in care was 36 years; 40% were male. The majority were married, had less than primary education, and less than 45 US dollars (3000 Indian Rupee) monthly income. The mean CD4 at presentation was 527 cells/mm3. The median time from ART eligibility to initiation was 5 and 2 months for before and after the PPP, respectively (p < 0.001). Becoming eligible after PPP was associated with more rapid treatment initiation (Hazard Ratio: [95% Confidence Interval] 1.49 [1.11, 1.99]). Moreover, among the 1639 persons lost to follow-up, more rapid loss was observed before the PPP (12.77 months) vs. after (13.37 months) (p = 0.25) and there was a significant interaction between ART status and calendar time before and after the PPP (p < 0.001). Being on treatment was associated with a lower likelihood of becoming lost before the PPP (HR: [95% CI] 0.33 [0.27, 0.42]), but this association was reversed after the PPP (HR: [95% CI] 1.77 [1.54, 2.04]), p-value for interaction <0.001. Treatment response measured by CD4 was comparable before and after the PPP (p = 0.088). Our findings suggest that PPP models of ART delivery may improve HIV treatment initiation and loss to follow-up without compromising the effectiveness of treatment. Efforts to expand these system-level interventions should be considered with on-going evaluation.

HIV/AIDS in women and children in India.

Management of HIV in India has significantly improved with many international and local programmes supporting prevention and treatment. However, there are areas in India where women and children living with HIV endure a myriad of medical, psychological and social challenges. Women in rural poor areas in India have little control over important aspects of their life. Often, they have little decision-making powers within their families on matters that affect them personally. They find themselves unable to negotiate to protect themselves from harm or risk of infection. Those who are known to have contracted HIV are reluctant to access health care for fear of discrimination and marginalization, leading to a disproportionate death rate in HIV women. India is arguably home to the largest number of orphans of the HIV epidemic. These children face an impenetrable barrier in many Indian societies and endure stigmatization. This situation encourages concealment of the disease and discourages children and their guardians from accessing available essential services. This article provides an overview of the relevant literature and presents an insight into a complex mix of issues that arise directly out of the HIV diagnosis, including the role of social attitudes in the spread of HIV, and in creating barriers to accessing care. The review identifies international programmes and local initiatives that have ensured better access to antiretroviral therapy and have led to prolonged survival and reduction in the vertical transmission of HIV in India.

Effectiveness of symptom screening and incidence of tuberculosis among adults and children living with HIV infection in India.

BACKGROUND: WHO recommends the use of a simplified symptom-based algorithm for screening for tuberculosis (TB) among people living with HIV (PLHIV). We assessed the feasibility and effectiveness of this algorithm and determined the prevalence and incidence of TB among PLHIV attending antiretroviral treatment (ART) centres in India. METHODS: We did a prospective multicentric implementation research study in four states of India. To rule out TB, we administered the WHO symptom-screen algorithm to all PLHIV every month for 6 months. If they were found to be symptomatic any time during this period, they were referred for investigations for TB. A case of TB diagnosed during the first month of screening was taken as a prevalent case while those detected TB in the subsequent 5 months were considered cases of incident TB. We calculated the incidence rate using the person-years method. Results . Between May 2012 and October 2013, a total of 6099 adults and 1662 children living with HIV were screened for TB at the ART centres of four states. Of the 6099 adult PLHIV, 1815 (30%) had at least one symptom suggestive of TB, of whom only 634 (35%) were referred for investigations of TB. Of those referred, 97 (15%) PLHIV were diagnosed with TB. Overall, the prevalence of undiagnosed TB was 0.84 person-years and in the subsequent period, the incidence of TB was 2.4/100 person-years (95% CI 1.90-3.10). Among 1662 children, 434 (26%) had at least one symptom suggestive of TB. But only 57 (13%) children were referred for investigations of TB and 13 (23%) of them were diagnosed with TB. The prevalence of TB among children was 0.5% and its incidence among them was 2.7/100 person-years (95% CI 1.60-4.30). CONCLUSION: Prevalence and incidence of TB is high among PLHIV attending ART centres. This emphasizes the need to strengthen regular screening for symptoms of TB and further referral of those symptomatic for diagnosis of TB.

Paediatric HIV--trends & challenges.

With the availability of antiretroviral therapy (ART), HIV infection, which was once considered a progressively fatal illness, has now become a chronic treatable condition in children, as in adults. However, the challenges these children are forced to face are far more daunting. The most significant shortcoming in the response to paediatric HIV remains the woefully inadequate prevention of mother-to-child transmission (PMTCT), allowing a large number of children to be born with HIV in the first place, in spite of it being largely preventable. In the west, mother-to-child transmission has been virtually eliminated; however, in resource-limited settings where >95 per cent of all vertical transmissions take place, still an infected infants continue to be born. There are several barriers to efficient management: delayed infant diagnosis, lack of appropriate paediatric formulations, lack of skilled health personnel, etc. Poorly developed immunity allows greater dissemination throughout various organs. There is an increased frequency of malnutrition and infections that may be more persistent, severe and less responsive to treatment. In addition, these growing children are left with inescapable challenges of facing not only lifelong adherence with complex treatment regimens, but also enormous psychosocial, mental and neuro-cognitive issues. These unique challenges must be recognized and understood in order to provide appropriate holistic management enabling them to become productive citizens of tomorrow. To address these multi-factorial issues, there is an urgent need for a concerted, sustainable and multi-pronged national and global response.

Safety, tolerability and effectiveness of generic HAART in HIV-infected children in South India.

HIV-infected children in resource-limited settings are increasingly gaining greater access to highly active antiretroviral therapy (HAART) but documented longitudinal data remains limited. We aimed to study the clinical and immunological outcomes among 67 South Indian HIV-infected children with >18 months of follow-up on HAART at a tertiary HIV care program. The median CD4 cell count at enrolment was 290 cells microl(-1) and at treatment initiation was 225 cells microl(-1). Patients demonstrated a significant rise in their CD4 cell counts between treatment initiation and after 6 months (701 cells microll(-1); p = 0.007), 12 months (741 cells microl(-1); p = 0.037), and 18 months of therapy (718 cells microl(-1); p = 0.005). The most common adverse events to therapy were nausea (20.9%) and rash (25.4%). Over one-fifth of patients (25.4%) substituted therapy due to toxicities and 19.4% of patients switched to second-line protease inhibitor-containing regimens. In this South Indian pediatric cohort, generic HAART was safe, effective and relatively well tolerated.

Transition of Children with Perinatally Acquired HIV-Infection into Adulthood: Social Outcome and Quality of Life.

OBJECTIVES: In India, access to free anti-retroviral therapy has improved the survival of perinatally human immunodeficiency virus (HIV) infected children resulting in the transition of many such children to adulthood. This study aims to understand the social-outcomes and quality of life (QOL) among these adults. METHODS: This cross-sectional study was conducted in two tertiary HIV care centers in south India. Perinatally HIV-infected adults aged >18 y were enrolled after obtaining consent. Data were collected by questionnaire based interviews for social outcomes and WHO Quality of Life-BREF (WHOQOL-BREF) for QOL. The social-outcome indicators monitored pertained to family support, educational qualification and occupational, economic, and marital status. RESULTS: The mean age of 107 participants was 18·9 ± 1·1y. The school drop-out rate was 58%. Sixty-two percent were double orphans. Forty-three-percent of the participants were employed with mean per-capita monthly income of Rs.4105 ± 2979 ($65·2 ± 47·3). Fourteen-percent of the participants were married, or in a relationship, and a majority of them, 93%, were females. For QOL, the mean raw score was highest for social relationship (15·79). Relative to studying subjects, a higher proportion of school dropouts scored poorly in social relationship (42% vs.14·8%; Chi-square = 5·28; p = 0·02) and environmental QOL (46% vs.19·6%;Chi-square = 8·09; p = 0·004). The proportion of subjects with a poor physical health QOL was higher among those with a per-capita monthly income above the national average than those with below the national average (69% vs.33·3%; Chi-square = 5·27; p = 0·02). CONCLUSIONS: Though clinico-immunological disease was stable in these perinatally HIV-infected young adults, their social-outcomes pertaining to education, occupation, income, and family support were poor. Factors like education, parental care, and income of the subjects were associated with poor QOL.

Assessment of neurological soft signs in pediatric patients with HIV infection.

BACKGROUND: Children and adolescents comprise a significant proportion of people living with HIV. The effects of HIV on the growing brain have generated interest among researchers in this field. Deficits arising during this crucial phase of neuromaturation due to HIV infection need to be assessed and addressed. Neurological soft signs (NSSs) can act as a proxy marker for underlying neuropsychological deficits. The present study aims to study the NSSs in pediatric patients with HIV and compare with healthy controls (HCs). MATERIALS AND METHODS: Forty-eight children aged between 6 and 16 years diagnosed with HIV were selected by purposive sampling, and the Physical and Neurological Examination of Soft Signs (PANESS) scale was applied. Fifty children matched by age and sex were recruited from a nearby school, and the PANESS scale was applied. Children were divided into age- and gender-specific groups. The outcome scores of cases and controls groups were compared. RESULTS: Males and females aged 13-16 years with HIV showed more soft signs as compared to HCs, with respect to gait errors, dysrhythmia, impersistence, speed of repetitive and sequenced movements, overflow with gaits, overflow with sequenced movements, total overflow, and overflow in excess of age. The differences in scores were less marked in younger age groups among both the genders. CONCLUSIONS: The persistence of NSSs in older age group in HIV-infected children may point toward the presence of HIV-associated neurological disorder.

Clinical manifestations of HIV infected children.

OBJECTIVE: Heterosexual contact is the predominant mode of transmission among adults in India with an increasing number of women of childbearing age becoming infected with HIV. Consequently, children in India increasingly getting infected, primarily from vertical transmission. A retrospective review of the profile of HIV infected children attending an HIV clinic in South India is reported. METHODS: All HIV-infected children under 15 years of age at the time of first presentation and managed at this center between June 1996 and June 2000 are included in this report. Socio-demographic characteristics and clinical manifestation were collected in a precoded proforme. A complete physical examination and baseline laboratory investigations were performed at entry into the clinic and at subsequent follow-up. RESULTS: Fifty-eight HIV-infected children were included: thirty-nine (67.2%) were male with mean age 4 years. Perinatal transmission was the predominant mode of HIV acquisition (67%). Common clinical manifestations in these children at presentation included oral candidiasis (43%), pulmonary tuberculosis (35%), recurrent respiratory infections (26%), bacterial skin infection (21%), papulo-pruritic dermatitis (19%), hepatosplenomegaly and lymphadenopathy (14%) each and chronic diarrhea (7%). CONCLUSION: An understanding of the epidemiology of pediatric HIV infection may reveal opportunities to reduce and perhaps eliminate perinatal transmission. Knowledge of clinical manifestations in this setting will help physicians meet the management challenges presented by HIV infected children.

Regression of attained milestones in an HIV infected infant.

We report a case of an 18-month-old child with regression of attained developmental milestones as a manifestation of HIV encephalopathy. This is the first such report in Indian literature. Commencing antiretroviral therapy in this child resulted in arrest of further regression of milestones. This alerts pediatricians to be aware that early developmental delay and regression may be a presenting manifestation of HIV infection in a child.

Ocular and systemic lesions in children with HIV.

The spectrum of ocular lesions in children with HIV infection is different from that seen in adults. Ocular lesions in pediatric AIDS patients have not been studied in India. We analyzed the clinical profile, demographic characteristics, ocular and systemic lesions in children with AIDS seen in a referral eye institute in India. The clinical profile and demographic features were studied and complete ocular examination was done. Systemic findings were evaluated at an AIDS care center and recorded in a precoded proforma. Out of the 218 cases of HIV infection seen at our hospital between December 1993 and October 1999, 12 (5.50%) were below 15 years of age. Seven (58.33%) were males and 5 (41.66%) were females with the mean age of 6.5 years and median age of 6.2 years. Vertical transmission was the most common mode of infection (58.33%). Seven (58.33%) of these patients had systemic infection, the most common being pulmonary tuberculosis (42.85%). Ocular lesions were found in 6 (50%) patients. The most common ocular lesions were anterior uveitis and cytomegalovirus retinitis (CMV) (33%) followed by retinal detachment (16.66%) and vitreous hemorrhage (16.66%). High prevalence of ocular lesions in pediatric AIDS patients in India in a referral eye centre was observed. The most common lesions were anterior uveitis followed by CMV retinitis. The management in such cases was often challenging in a developing country like India.

Psychosocial Issues of Children Infected with HIV/AIDS.

The chronic medical conditions in the paediatric population pose a range of potential psychosocial challenges not only to the child, but also to the family members and health care providers. This paper comprehensively reviews the psychosocial issues of children infected with HIV and AIDS and offer some of the strategies to address the issues comprehensively by multidisciplinary team.

Adolescents living with HIV in India - the clock is ticking.

The term "Adolescence" literally means "to emerge" or "to attain identity" and is essentially the period of rapid physical and psychological development starting from the onset of puberty to complete growth. All adolescents go through a myriad of physical, psychological, neurobehavioural, hormonal and social developmental changes. Given the social taboos often surrounding puberty, the lives of millions of adolescents worldwide are at risk because they do not have the information, skills, health services and support they need to go through the enormous, rapid changes that adolescence brings. A HIV infected adolescent particularly presents enormous challenges in the current cultural and social context of India. The distinct groups of adolescents in the context of HIV are those who were infected at birth and survived and those who became infected during adolescence. Risk factors and situations for adolescents contracting HIV infection are life on streets, lack of adult love/care and support, extreme poverty, child trafficking, migrant population, exploitation in terms of sex and labor. HIV-infected adolescents with long standing HIV infection often face considerable physical challenges - delayed growth and development, late puberty, stunting/wasting, malnutrition, etc. Added to this are many other challenges related mainly to disclosure of HIV status, developmental delay, and transition from pediatric to adult care, including the choice of appropriate treatment regimens and adherence. Psychological and social factors deeply impact the ability to deal with the illness and must be addressed at all levels to encourage and support this vulnerable group.