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

<p>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.</p> <p>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.</p> <p>Findings: In the primary health care programme of HIV treatment 346 children <16 years of age initiated HAART by 2008; 245(70.8%) were aged 10 years or younger, and only 2(<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%.</p> <p>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.</p&gt

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

Early ART-initiation and longer ART duration reduces HIV-1 proviral DNA levels in children from the CHER trial

BACKGROUND: Reduction of the reservoir of latent HIV-infected cells might increase the possibility of long-term remission in individuals living with HIV. We investigated factors associated with HIV-1 proviral DNA levels in children receiving different antiretroviral therapy (ART) strategies in the children with HIV early antiretroviral therapy (CHER) trial. METHODS: Infants with HIV  <  12 weeks old with CD4%  ≥  25% were randomized in the CHER trial to early limited ART for 40 or 96 weeks (ART-40 W, ART-96 W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40 W/ART-96 W, ART was started/re-started for clinical progression or CD4%  <  25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received  ≥  24 weeks ART and two consecutive undetectable HIV-1 RNA 12-24 weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96 W at week 96, and in all arms at week 248. Factors associated with HIV-1 proviral DNA levels were evaluated using linear regression. FINDINGS: Longer duration of ART was significantly associated with lower HIV-1 proviral DNA at both 96 (p  =  0.0003) and 248 weeks (p  =  0.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p  =  0.0225) and 248 weeks (p  =  0.0398). Week 248 HIV-1 proviral DNA was significantly higher in those with positive HIV-1 serology at week 84 than those with negative serology (p  =  0.0042). INTEPRETATION: Longer ART duration is key to HIV-1 proviral DNA reduction. Further understanding is needed of the effects of "immune-attenuation" through early HIV-1 exposure. FUNDING: Wellcome Trust, National Institutes of Health, Medical Research Council

Synergies, tensions and challenges in HIV prevention, treatment and cure research: exploratory conversations with HIV experts in South Africa

Background: The ethical concerns associated with HIV prevention and treatment research have been widely explored in South Africa over the past 3 decades. However, HIV cure research is relatively new to the region and significant ethical and social challenges are anticipated. There has been no published empirical enquiry in Africa into key informant perspectives on HIV cure research. Consequently, this study was conducted to gain preliminary data from South African HIV clinicians, researchers and activists. Methods: In-depth interviews were conducted on a purposive sample of fourteen key informants in South Africa. Audiotaped interviews were transcribed verbatim with concurrent thematic analysis. The perspectives of HIV clinicians, researchers and activists were captured. Analyst triangulation occurred as the data were analysed by three authors independently. Results: The rapid evolution of HIV cure research agendas was prominent with participants expressing some concern that the global North was driving the cure agenda. Participants described a symbiotic relationship between cure, treatment and prevention research necessitating collaboration. Assessing and managing knowledge and expectations around HIV cure research emerged as a central theme related to challenges to constructing ‘cure’ - how patients understand the idea of cure is important in explaining the complexity of cure research especially in the South African context where understanding of science is often challenging. Managing expectations and avoiding curative misconception will have implications for consent processes. Unique strategies in cure research could include treatment interruption, which has the potential to create therapeutic and ethical conflict and will be perceived as a significant risk. Ethical challenges in cure research will impact on informed consent and community engagement. Conclusions: It was encouraging to note the desire for synergy amongst researchers and clinicians working in the fields of prevention, treatment and cure. Translation of complex HIV cure science into lay language is critical. Moving forward, RECs must be adequately constituted with scientific expertise and community representation when reviewing cure protocols. It is hoped that knowledge and resource sharing in the context of collaboration between research scientists working in cure and those working in treatment and prevention will accelerate progress towards cur

Naïve B-cell Output in Hiv-infected and Hiv-uninfected Children

BACKGROUND: In this study, we aimed to quantify KREC (kappa-deleting recombination excision circles) levels and naïve B-cell output in healthy HIV-uninfected children, compared with HIV-infected South African children, before and after starting ART (anti-retroviral therapy). SETTING: Samples were acquired from a Child Wellness Clinic (n=288 HIV-uninfected South African children, 2 weeks - 12 years) and the Children with HIV and Early Antiretroviral Therapy (CHER) trial (n=153 HIV-infected South African children, 7 weeks - 8 years). METHODS: Naïve B-cell output was estimated using a mathematical model combining KREC levels to reflect B-cell emigration into the circulation, flow cytometry measures of naïve un-switched B-cells to quantify total body naïve B-cells, and their rates of proliferation using the intracellular marker Ki67. RESULTS: Naïve B-cell output increases from birth to 1 year, followed by a decline and plateau into late childhood. HIV-infected children on or off ART had higher naïve B-cell outputs than their uninfected counterparts (p=0.01 and p=0.04). CONCLUSIONS: This is the first study to present reference ranges for measurements of KRECs and naïve B-cell output in healthy and HIV-infected children. Comparison between HIV-uninfected healthy children and HIV-infected children suggest that HIV may increase naïve B-cell output. Further work is required to fully understand the mechanisms involved and clinical value of measuring naïve B-cell output in children.  

HIV Testing for Children in Resource-Limited Settings: What Are We Waiting For?

Scott Kellerman and Shaffiq Essajee argue that the time has come to increase access to HIV testing for children, especially in sub-Saharan Africa