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 of Early Infant Diagnosis of HIV in Resource-Limited Settings: The ANRS 12140-PEDIACAM Study in Cameroon

BACKGROUND: Early infant diagnosis (EID) of HIV is a key-point for the implementation of early HAART, associated with lower mortality in HIV-infected infants. We evaluated the EID process of HIV according to national recommendations, in urban areas of Cameroon. METHODS/FINDINGS: The ANRS12140-PEDIACAM study is a multisite cohort in which infants born to HIV-infected mothers were included before the 8(th) day of life and followed. Collection of samples for HIV DNA/RNA-PCR was planned at 6 weeks together with routine vaccination. The HIV test result was expected to be available at 10 weeks. A positive or indeterminate test result was confirmed by a second test on a different sample. Systematic HAART was offered to HIV-infected infants identified. The EID process was considered complete if infants were tested and HIV results provided to mothers/family before 7 months of age. During 2007-2009, 1587 mother-infant pairs were included in three referral hospitals; most infants (n = 1423, 89.7%) were tested for HIV, at a median age of 1.5 months (IQR, 1.4-1.6). Among them, 51 (3.6%) were HIV-infected. Overall, 1331 (83.9%) completed the process by returning for the result before 7 months (median age: 2.5 months (IQR, 2.4-3.0)). Incomplete process, that is test not performed, or result of test not provided or provided late to the family, was independently associated with late HIV diagnosis during pregnancy (adjusted odds ratio (aOR) = 1.8, 95%CI: 1.1 to 2.9, p = 0.01), absence of PMTCT prophylaxis (aOR = 2.4, 95%CI: 1.4 to 4.3, p = 0.002), and emergency caesarean section (aOR = 2.5, 95%CI: 1.5 to 4.3, p = 0.001). CONCLUSIONS: In urban areas of Cameroon, HIV-infected women diagnosed sufficiently early during pregnancy opt to benefit from EID whatever their socio-economic, marital or disclosure status. Reduction of non optimal diagnosis process should focus on women with late HIV diagnosis during pregnancy especially if they did not receive any PMTCT, or if complications occurred at delivery

Introducing a multi-site program for early diagnosis of HIV infection among HIV-exposed infants in Tanzania

<p>Abstract</p> <p>Background</p> <p>In Tanzania, less than a third of HIV infected children estimated to be in need of antiretroviral therapy (ART) are receiving it. In this setting where other infections and malnutrition mimic signs and symptoms of AIDS, early diagnosis of HIV among HIV-exposed infants without specialized virologic testing can be a complex process. We aimed to introduce an Early Infant Diagnosis (EID) pilot program using HIV DNA Polymerase Chain Reaction (PCR) testing with the intent of making EID nationally available based on lessons learned in the first 6 months of implementation.</p> <p>Methods</p> <p>In September 2006, a molecular biology laboratory at Bugando Medical Center was established in order to perform HIV DNA PCR testing using Dried Blood Spots (DBS). Ninety- six health workers from 4 health facilities were trained in the identification and care of HIV-exposed infants, HIV testing algorithms and collection of DBS samples. Paper-based tracking systems for monitoring the program that fed into a simple electronic database were introduced at the sites and in the laboratory. Time from birth to first HIV DNA PCR testing and to receipt of test results were assessed using Kaplan-Meier curves.</p> <p>Results</p> <p>From October 2006 to March 2007, 510 HIV-exposed infants were identified from the 4 health facilities. Of these, 441(87%) infants had an HIV DNA PCR test at a median age of 4 months (IQR 1 to 8 months) and 75(17%) were PCR positive. Parents/guardians for a total of 242(55%) HIV-exposed infants returned to receive PCR test results, including 51/75 (68%) of those PCR positive, 187/361 (52%) of the PCR negative, and 4/5 (80%) of those with indeterminate PCR results. The median time between blood draw for PCR testing and receipt of test results by the parent or guardian was 5 weeks (range <1 week to 14 weeks) among children who tested PCR positive and 10 weeks (range <1 week to 21 weeks) for those that tested PCR negative.</p> <p>Conclusions</p> <p>The EID pilot program successfully introduced systems for identification of HIV-exposed infants. There was a high response as hundreds of HIV-exposed infants were registered and tested in a 6 month period. Challenges included the large proportion of parents not returning for PCR test results. Experience from the pilot phase has informed the national roll-out of the EID program currently underway in Tanzania.</p

Serological Testing Versus Other Strategies for Diagnosis of Active Tuberculosis in India: A Cost-Effectiveness Analysis

This cost-effectiveness study shows that sputum smear microscopy is the most cost-effective test for active tuberculosis (TB) in India, and liquid culture plus microscopy is more cost-effective for TB diagnosis than serological tests

Promising outcomes of a national programme for the prevention of mother-to-child HIV transmission in Addis Ababa: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Prevention of Mother-to-Child HIV Transmission (PMTCT) is still the most effective intervention in combating new HIV infections. In 2008, revised national PMTCT guidelines that incorporated new policies on HIV counselling and testing, antiretroviral prophylaxis regimen and infant HIV diagnosis came into effect in Ethiopia. In the present study we have examined trends in PMTCT service utilization and assessed the rate of MTCT in relation to policy changes in the national PMTCT programme.</p> <p>Methods</p> <p>Reports from February 2004 to August 2009 were reviewed in 10 sub-cities in Addis Ababa, Ethiopia. The data was collected from May to October 2009.</p> <p>Results</p> <p>The proportion of women who received HIV counselling and testing among new antenatal care attendees increased from 50.7% (95% CI 50.2-51.2) in 2007 to 84.5% (95% CI 84.1-84.9) in 2009 following the shift to routine opt-out testing. Nevertheless, in 2009 only 53.7% of the positive women and 40.7% of their infants received antiretroviral prophylaxis. The HIV prevalence among antenatal attendees decreased significantly from 10.5% in 2004 to 4.6% in 2009 in parallel to the increased number of women being tested. The HIV positive women were over 18 times (RR 18.5, p < 0.0001) more likely to be referred for treatment, care and support in 2009 than in 2004. The proportion of partners tested for HIV decreased by 14% in 2009 compared to 2004, although the absolute number was increasing year by year. Only 10.6% (95% CI 9.9-11.2) of the HIV positive women completed their follow up to infant HIV testing. The cumulative probability of HIV infection among babies on single dose nevirapine regimen who were tested at >=18 months was 15.0% (95% CI 9.8-22.1) in 2007, whereas it was 8.2% (95% CI 5.55-11.97) among babies on Zidovudine regimen who were tested at >=45 days in 2009.</p> <p>Conclusion</p> <p>The paper demonstrates trends in PMTCT service utilization in relation to changing policy. There is marked improvement in HIV counselling and testing service utilization, especially after the policy shift to routine opt-out testing. However, despite policy changes, the ARV prophylaxis uptake, the loss to follow up and the partner testing have remained unchanged across the years. This should be a matter of immediate concern and a topic for further research.</p

Metabolomic analyses of Leishmania reveal multiple species differences and large differences in amino acid metabolism

Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts

Women's Preferences Regarding Infant or Maternal Antiretroviral Prophylaxis for Prevention of Mother-To-Child Transmission of HIV during Breastfeeding and Their Views on Option B+ in Dar es Salaam, Tanzania.

The WHO 2010 guidelines for prevention of mother-to-child transmission (PMTCT) of HIV recommended prophylactic antiretroviral treatment (ART) either for infants (Option A) or mothers (Option B) during breastfeeding for pregnant women with a CD4 count of >350 cell/µL in low-income countries. In 2012, WHO proposed that all HIV-infected pregnant women should receive triple ART for life (B+) irrespective of CD4 count. Tanzania has recently switched from Option A to B+, with a few centers practicing B. However, more information on the real-life feasibility of these options is needed. This qualitative study explored women's preferences for Option A vs B and their views on Option B+ in Dar es Salaam, Tanzania. We conducted four focus group discussions with a total of 27 pregnant women with unknown HIV status, attending reproductive and child health clinics, and 31 in-depth interviews among HIV-infected pregnant and post-delivery women, 17 of whom were also asked about B+. Most participants were in favor of Option B compared to A. The main reasons for choosing Option B were: HIV-associated stigma, fear of drug side-effects on infants and difficult logistics for postnatal drug adherence. Some of the women asked about B+ favored it as they agreed that they would eventually need ART for their own survival. Some were against B+ anticipating loss of motivation after protecting the child, fearing drug side-effects and not feeling ready to embark on lifelong medication. Some were undecided. Option B was preferred. Since Tanzania has recently adopted Option B+, women with CD4 counts of >350 cell/µL should be counseled about the possibility to "opt-out" from ART after cessation of breastfeeding. Drug safety and benefits, economic concerns and available resources for laboratory monitoring and evaluation should be addressed during B+ implementation to enhance long-term feasibility and effectiveness

Lack of Knowledge of HIV Status a Major Barrier to HIV Prevention, Care and Treatment Efforts in Kenya: Results from a Nationally Representative Study

BACKGROUND: We analyzed HIV testing rates, prevalence of undiagnosed HIV, and predictors of testing in the Kenya AIDS Indicator Survey (KAIS) 2007. METHODS: KAIS was a nationally representative sero-survey that included demographic and behavioral indicators and testing for HIV, HSV-2, syphilis, and CD4 cell counts in the population aged 15-64 years. We used gender-specific multivariable regression models to identify factors independently associated with HIV testing in sexually active persons. RESULTS: Of 19,840 eligible persons, 80% consented to interviews and blood specimen collection. National HIV prevalence was 7.1% (95% CI 6.5-7.7). Among ever sexually active persons, 27.4% (95% CI 25.6-29.2) of men and 44.2% (95% CI 42.5-46.0) of women reported previous HIV testing. Among HIV-infected persons, 83.6% (95% CI 76.2-91.0) were unaware of their HIV infection. Among sexually active women aged 15-49 years, 48.7% (95% CI 46.8-50.6) had their last HIV test during antenatal care (ANC). In multivariable analyses, the adjusted odds ratio (AOR) for ever HIV testing in women ≥35 versus 15-19 years was 0.2 (95% CI: 0.1-0.3; p<0.0001). Other independent associations with ever HIV testing included urban residence (AOR 1.6, 95% CI: 1.2-2.0; p = 0.0005, women only), highest wealth index versus the four lower quintiles combined (AOR 1.8, 95% CI: 1.3-2.5; p = 0.0006, men only), and an increasing testing trend with higher levels of education. Missed opportunities for testing were identified during general or pregnancy-specific contacts with health facilities; 89% of adults said they would participate in home-based HIV testing. CONCLUSIONS: The vast majority of HIV-infected persons in Kenya are unaware of their HIV status, posing a major barrier to HIV prevention, care and treatment efforts. New approaches to HIV testing provision and education, including home-based testing, may increase coverage. Targeted interventions should involve sexually active men, sexually active women without access to ANC, and rural and disadvantaged populations

Early infant HIV-1 diagnosis programs in resource-limited settings: opportunities for improved outcomes and more cost-effective interventions

Early infant diagnosis (EID) of HIV-1 infection confers substantial benefits to HIV-infected and HIV-uninfected infants, to their families, and to programs providing prevention of mother-to-child transmission (PMTCT) services, but has been challenging to implement in resource-limited settings. In order to correctly inform parents/caregivers of infant infection status and link HIV-infected infants to care and treatment, a 'cascade' of events must successfully occur. A frequently cited barrier to expansion of EID programs is the cost of the required laboratory assays. However, substantial implementation barriers, as well as personnel and infrastructure requirements, exist at each step in the cascade. In this update, we review challenges to uptake at each step in the EID cascade, highlighting that even with the highest reported levels of uptake, nearly half of HIV-infected infants may not complete the cascade successfully. We next synthesize the available literature about the costs and cost effectiveness of EID programs; identify areas for future research; and place these findings within the context of the benefits and challenges to EID implementation in resource-limited settings

Assessment of utilization of provider-initiated HIV testing and counseling as an intervention for prevention of mother to child transmission of HIV and associated factors among pregnant women in Gondar town, North West Ethiopia

<p>Abstract</p> <p>Background</p> <p>Detection of maternal HIV infection early in pregnancy is critical for prevention of mother to child transmission of HIV/AIDS. Most efforts have focused on VCT as the primary means of encouraging people to become aware of their HIV status. However, its uptake is low in many parts of sub-Saharan Africa including Ethiopia. Provider-initiated HIV testing and counseling provides a critical opportunity to diagnose HIV infection, to begin chronic care, and to prevent mother to child transmission. However, little is known about its acceptance and associated factors among pregnant women in the country and particularly in the present study area.</p> <p>Methods</p> <p>Health institution based cross-sectional quantitative study was conducted in Gondar town from July 22-August 18, 2010. A total of 400 pregnant women were involved in the study using stratified sampling technique and multiple logistic regression analysis was employed using SPSS version 16.</p> <p>Results</p> <p>A total of 400 pregnant women actively participated in this study and 330 (82.5%) of them accepted provider-initiated HIV testing and counseling to be tested for HIV and 70(17.5%) of them refused. Acceptance of provider-initiated HIV testing and counseling was positively associated with greater number of antenatal care visits [Adj. OR (95%CI)=2.64(1.17, 5.95)], residing in the urban areas[Adj. OR (95%CI)=2.85(1.10, 7.41)], having comprehensive knowledge on HIV [Adj. OR (95%CI)=4.30(1.72, 10.73)], positive partners reaction for HIV positive result [Adj. OR (95%CI)=8.19(3.57, 18.80)] and having knowledge on prevention of mother to child transmission of HIV[Adj. OR (95%CI)=3.27(1.34, 7.94)], but negatively associated with increased maternal age and education level.</p> <p>Conclusion</p> <p>Utilization of provider-initiated HIV testing and counseling during antenatal care was relatively high among pregnant women in Gondar town. Couple counseling and HIV testing should be strengthened to promote provider-initiated HIV testing and counseling among male partners and to reduce HIV related violence of women from their partner and access to and consistent use of antenatal care should be improved to increase the uptake of provider-initiated HIV testing and counseling service.</p