Survey of children accessing HIV services in a high prevalence setting: time for adolescents to count?

OBJECTIVE: To establish the proportion of adolescents among children infected with human immunodeficiency virus (HIV) in Zimbabwe who receive HIV care and support, and what clinic staff perceives to be the main problems faced by HIV-infected children and adolescents. METHODS: In July 2008, we sent a questionnaire to all 131 facilities providing HIV care in Zimbabwe. In it we requested an age breakdown of the children (aged 0-19 years) registered for care and asked what were the two major problems faced by younger children (0-5 years) and adolescents (10-19 years). FINDINGS: Nationally, 115 (88%) facilities responded. In 98 (75%) that provided complete data, 196 032 patients were registered and 24 958 (13%) of them were children. Of children under HIV care, 33% were aged 0-4 years; 25%, 5-9 years; 25%, 10-14 years; and 17%, 15-19 years. Staff highlighted differences in the problems most commonly faced by younger children and adolescents. For younger children, such problems were malnutrition and lack of appropriate drugs (cited by 46% and 40% of clinics, respectively); for adolescents they concerned psychosocial issues and poor drug adherence (cited by 56% and 36%, respectively). CONCLUSION: Interventions for the large cohort of adolescents who are receiving HIV care in Zimbabwe need to target the psychosocial concerns and poor drug adherence reported by staff as being the main concerns in this age group

Association of pol Diversity with Antiretroviral Treatment Outcomes among HIV-Infected African Children

Background: In HIV-infected children, viral diversity tends to increase with age in the absence of antiretroviral treatment (ART). We measured HIV diversity in African children (ages 6–36 months) enrolled in a randomized clinical trial comparing two ART regimens (Cohort I of the P1060 trial). Children in this cohort were exposed to single dose nevirapine (sdNVP) at birth. Methods: HIV diversity was measured retrospectively using a high resolution melting (HRM) diversity assay. Samples were obtained from 139 children at the enrollment visit prior to ART initiation. Six regions of the HIV genome were analyzed: two in gag, one in pol, and three in env. A single numeric HRM score that reflects HIV diversity was generated for each region; composite HRM scores were also calculated (mean and median for all six regions). Results: In multivariable median regression models using backwards selection that started with demographic and clinical variables, older age was associated with higher HRM scores (higher HIV diversity) in pol (P = 0.005) and with higher mean (P = 0.014) and median (P<0.001) HRM scores. In multivariable models adjusted for age, pre-treatment HIV viral load, pre-treatment CD4%, and randomized treatment regimen, higher HRM scores in pol were associated with shorter time to virologic suppression (P = 0.016) and longer time to study endpoints (virologic failure [VF], VF/death, and VF/off study treatment; P<0.001 for all measures). Conclusions: In this cohort of sdNVP-exposed, ART-naïve African children, higher levels of HIV diversity in the HIV pol region prior to ART initiation were associated with better treatment outcomes

Need for timely paediatric HIV treatment within primary health care in rural South Africa

&lt;p&gt;Background: In areas where adult HIV prevalence has reached hyperendemic levels, many infants remain at risk of acquiring HIV infection. Timely access to care and treatment for HIV-infected infants and young children remains an important challenge. We explore the extent to which public sector roll-out has met the estimated need for paediatric treatment in a rural South African setting.&lt;/p&gt; &lt;p&gt;Methods: Local facility and population-based data were used to compare the number of HIV infected children accessing HAART before 2008, with estimates of those in need of treatment from a deterministic modeling approach. The impact of programmatic improvements on estimated numbers of children in need of treatment was assessed in sensitivity analyses.&lt;/p&gt; &lt;p&gt;Findings: In the primary health care programme of HIV treatment 346 children &#60;16 years of age initiated HAART by 2008; 245(70.8%) were aged 10 years or younger, and only 2(&#60;1%) under one year of age. Deterministic modeling predicted 2,561 HIV infected children aged 10 or younger to be alive within the area, of whom at least 521(20.3%) would have required immediate treatment. Were extended PMTCT uptake to reach 100% coverage, the annual number of infected infants could be reduced by 49.2%.&lt;/p&gt; &lt;p&gt;Conclusion: Despite progress in delivering decentralized HIV services to a rural sub-district in South Africa, substantial unmet need for treatment remains. In a local setting, very few children were initiated on treatment under 1 year of age and steps have now been taken to successfully improve early diagnosis and referral of infected infants.&lt;/p&gt

Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland

Objective: To assess factors at the start of antiretroviral therapy (ART) associated with long-term virological response in children. Design: Multicentre national cohort. Methods: Factors associated with viral load below 400 copies/ml by 12 months and virologic failure among children starting 3/4-drug ART in the UK/Irish Collaborative HIV Paediatric Study were assessed using Poisson models. Results: Nine hundred and ninety-seven children started ART at a median age of 7.7 years (inter-quartile range 2.9–11.7), 251 (25%) below 3 years: 411 (41%) with efavirenz and two nucleoside reverse transcriptase inhibitors (EFVþ2NRTIs), 264 (26%) with nevirapine and two NRTIs (NVPþ2NRTIs), 119 (12%; 106 NVP, 13 EFV) with non-nucleoside reverse transcriptase inhibitor and three NRTIs (NNRTIþ3NRTIs), and 203 (20%) with boosted protease inhibitor-based regimens. Median follow-up after ART initiation was 5.7 (3.0–8.8) years. Viral load was less than 400 copies/ml by 12 months in 92% [95% confidence interval (CI) 91–94%] of the children. Time to suppression was similar across regimens (P¼0.10), but faster over calendar time, with older age and lower baseline viral load. Three hundred and thirtynine (34%) children experienced virological failure. Although progression to failure varied by regimen (P<0.001) and was fastest for NVPþ2NRTIs regimens, risk after 2 years on therapy was similar for EFVþ2NRTIs and NVPþ2NRTIs, and lowest for NNRTIþ3NRTIs regimens (P-interaction¼0.03). Older age, earlier calendar periods and maternal ART exposure were associated with increased failure risk. Early treatment discontinuation for toxicity occurred more frequently for NVP-based regimens, but 5-year cumulative incidence was similar: 6.1% (95% CI 3.9–8.9%) NVP, 8.3% (95% CI 5.6–11.6) EFV, and 9.8% (95% CI 5.7–15.3%) protease inhibitor-based regimens (P¼0.48). Conclusion: Viral load suppression by 12 months was high with all regimens. NVPþ3NRTIs regimens were particularly efficacious in the longer term and may be a good alternative to protease inhibitor-based ART in young children

Hepatitis B virus vaccination in HIV-1-infected young adults: A tool to reduce the size of HIV-1 reservoirs?

During anti-retroviral therapy (ART) HIV-1 persists in cellular reservoirs, mostly represented by CD4+ memory T cells. Several approaches are currently being undertaken to develop a cure for HIV-1 infection through elimination (or reduction) of these reservoirs. Few studies have so far been conducted to assess the possibility of reducing the size of HIV-1 reservoirs through vaccination in virologically controlled HIV-1-infected children. We recently conducted a vaccination study with a combined hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccine in 22 HIV-1-infected children. We assessed the size of the virus reservoir, measured as total HIV-1 DNA copies in blood cells, pre- and postvaccination. In addition, we investigated by immunostaining whether the frequencies of CD4+ and CD8+ T cells and parameters of immune activation and proliferation on these cells were modulated by vaccination. At 1 month from the last vaccination dose, we found that 20 out of 22 children mounted a serological response to HBV; a majority of children had antibodies against HAV at baseline. The number of HIV-1 DNA copies in blood at 1 month postvaccination was reduced in comparison to baseline although this reduction was not statistically significant. A significant reduction of HIV-1 DNA copies in blood following vaccination was found in 12 children. The frequencies of CD4+ (naïve, effector memory) and CD8+ (central memory) T-cell subpopulations changed following vaccinations and a reduction in the activation and proliferation pattern of these cells was also noticed. Multivariate linear regression analysis revealed that the frequency of CD8+ effector memory T cells prior to vaccination was strongly predictive of the reduction of HIV-1 DNA copies in blood following vaccination of the 22 HIV-1-infected children. The results of this study suggest a beneficial effect of vaccination to reduce the size of virus reservoir in HIV-1-infected children receiving ART. A reduced frequency of activated CD4+ cells and an increase in central memory CD8+ T cells were associated with this finding. Further studies should assess whether vaccination is a possible tool to reduce HIV-1 reservoirs

Early Infant Diagnosis of HIV in Three Regions in Tanzania; Successes and Challenges.

By the end of 2009 an estimated 2.5 million children worldwide were living with HIV-1, mostly as a consequence of vertical transmission, and more than 90% of these children live in sub-Saharan Africa. In 2008 the World Health Organization (WHO), recommended early initiation of Highly Active Antiretroviral Therapy (HAART) to all HIV infected infants diagnosed within the first year of life, and since 2010, within the first two years of life, irrespective of CD4 count or WHO clinical stage. The study aims were to describe implementation of EID programs in three Tanzanian regions with differences in HIV prevalences and logistical set-up with regard to HIV DNA testing. Data were obtained by review of the prevention from mother to child transmission of HIV (PMTCT) registers from 2009-2011 at the Reproductive and Child Health Clinics (RCH) and from the databases from the Care and Treatment Clinics (CTC) in all the three regions; Kilimanjaro, Mbeya and Tanga. Statistical tests used were Poisson regression model and rank sum test. During the period of 2009 - 2011 a total of 4,860 exposed infants were registered from the reviewed sites, of whom 4,292 (88.3%) were screened for HIV infection. Overall proportion of tested infants in the three regions increased from 77.2% in 2009 to 97.8% in 2011. A total of 452 (10.5%) were found to be HIV infected (judged by the result of the first test). The prevalence of HIV infection among infants was higher in Mbeya when compared to Kilimanjaro region RR = 1.872 (95%CI = 1.408 - 2.543) p < 0.001. However sample turnaround time was significantly shorter in both Mbeya (2.7 weeks) and Tanga (5.0 weeks) as compared to Kilimanjaro (7.0 weeks), p=<0.001. A substantial of loss to follow-up (LTFU) was evident at all stages of EID services in the period of 2009 to 2011. Among the infants who were receiving treatment, 61% were found to be LFTU during the review period. The study showed an increase in testing of HIV exposed infants within the three years, there is large variations of HIV prevalence among the regions. Challenges like; sample turnaround time and LTFU must be overcome before this can translate into the intended goal of early initiation of lifelong lifesaving antiretroviral therapy for the infants

Feasibility and acceptability of postpartum voluntary counselling and testing (PPVCT) in a large tertiary hospital in the South African setting

Objective. To demonstrate the feasibility and acceptability of introducing postpartum voluntary counselling and testing (PPVCT) and the provision of post-exposure nevirapine prophylaxis (PEP) to HIV-exposed infants whose mothers did not receive any antiretroviral prophylaxis to prevent mother-to-child transmission (PMTCT) in a large, tertiary hospital in the South African setting. Design. Observational, interventional study. Setting. The programme was implemented at Chris Hani Baragwanath Hospital (tertiary referral centre) in Soweto, South Africa, following a study that established the efficacy of a postpartum regimen of PEP in PMTCT. Participants. From January 2003 to December 2004, 7 500 women who delivered at Chris Hani Baragwanath Hospital without a documented HIV-1 result were identified in the postnatal wards. PPVCT was offered to all eligible participants. Intervention. On-site HIV rapid tests were performed on all women who agreed to testing. For those women testing HIV-1 positive, a single dose of nevirapine syrup was offered to their infants as PEP within 72 hours after delivery. Infant feeding counselling, assistance with follow-up care and support programmes were also offered. Main outcome. From January 2003 to December 2004, 34 776 deliveries occurred at Chris Hani Baragwanath Hospital. Of these, 7 500 (21.5%) had no documented HIV status. After delivery 5 751 (76.7%) women were offered VCT, and of these 3 794 (66%) accepted testing. Of these women, 1 294 (34%) tested HIV positive and 1 243 (96%) women accepted the administration of single-dose nevirapine to their infants. Conclusions. The uptake of PPVCT is comparable to that seen in established antenatal VCT despite the numerous challenges PPVCT presents. This suggests that PPVCT is both an acceptable and a feasible option in a busy, resource-limited setting and remains an important strategy in PMTCT in untreated individuals. Southern African Journal of HIV Medicine Vol. 6 (2) 2005: pp. 8-1

HIV and the urban homeless in Johannesburg

Background. There are few data on HIV prevalence and risk factors among inner-city homeless and marginally housed individuals in South Africa.Methods. We recruited 136 adults from a Johannesburg inner-city homeless clinic; mean age was 32.4 years, 129 (95%) were male, and 90 (66%) were of South African nationality. Participants were tested for HIV and answered a short demographic survey. Descriptive statistics and uni- and multivariate regression analyses were used for data analysis.Results. The HIV prevalence in the cohort was 23.5%. Transactional sex, relationship status, number of concurrent sexual partners, condom usage and history of previously treated sexually transmitted infections (STIs), living on the street, the use of alcohol or drugs, and previous exposure to voluntary counselling and testing (VCT), were not significant risk factors for HIVpositivity. Statistically significant HIV risk factors on multivariate analysis included the presence of an STI (odds ratio (OR) 5.6; p&lt;0.01) and unemployment (OR 6.7; p&lt;0.01). South African nationality was a significant risk factor on univariate analysis (OR 2.99; p&lt;0.05), but not on multivariate analysis (OR 2.2; p=0.17).Conclusion. The HIV prevalence in the sample did not differ appreciably from HIV prevalence estimates in other at-risk populations in similar settings, suggesting that homelessness in a South African city alone may not be a significant risk factor for HIV infection. HIV prevention efforts cannot be restricted to behaviour change programmes, but must be more holistic, recognising the protective role that employment has on HIV incidence