Monitoring Antiretroviral Therapy in HIV-Infected Children in Resource-Limited Countries: A Tale of Two Epidemics

Twenty-nine years into the HIV epidemic, several advances have been made; however, there remain several challenges particularly with pediatric HIV in resource-limited countries. The obstacles facing pediatric antiretroviral therapy (ART) delivery in resource-limited countries are multifaceted: lack of health care infrastructure, limited availability of pediatric drug formulations, lack of early HIV diagnostic and monitoring techniques, limited manpower with expertise in pediatric HIV care, limited donor funding, and competing public health priorities with limited health care budget. In this paper, the challenges with various ART monitoring tools in resource-limited countries are discussed. Noninvasive (e.g., patient, clinical events outcome, and adherence) and invasive (e.g., immunologic and virologic) monitoring tools are discussed. Several cheap and technically less complex laboratory tests for monitoring are becoming available. Funding agencies and country programs should invest in validating the use of current technologies to optimize pediatric HIV care in resource-limited countries

Cost effectiveness of option B plus for prevention of mother-to-child transmission of HIV in resource-limited countries: evidence from Kumasi, Ghana.

BackgroundAchieving the goal of eliminating mother-to-child HIV transmission (MTCT) necessitates increased access to antiretroviral therapy (ART) for HIV-infected pregnant women. Option B provides ART through pregnancy and breastfeeding, whereas Option B+ recommends continuous ART regardless of CD4 count, thus potentially reducing MTCT during future pregnancies. Our objective was to compare maternal and pediatric health outcomes and cost-effectiveness of Option B+ versus Option B in Ghana.MethodsA decision-analytic model was developed to simulate HIV progression in mothers and transmission (in utero, during birth, or through breastfeeding) to current and all future children. Clinical parameters, including antenatal care access and fertility rates, were estimated from a retrospective review of 817 medical records at two hospitals in Ghana. Additional parameters were obtained from published literature. Modeled outcomes include HIV infections averted among newborn children, quality-adjusted life-years (QALYs), and cost-effectiveness ratios.ResultsHIV-infected women in Ghana have a lifetime average of 2.3 children (SD 1.3). Projected maternal life expectancy under Option B+ is 16.1 years, versus 16.0 years with Option B, yielding a gain of 0.1 maternal QALYs and 3.2 additional QALYs per child. Despite higher initial ART costs, Option B+ costs $785/QALY gained, a value considered very cost-effective by World Health Organization benchmarks. Widespread implementation of Option B+ in Ghana could theoretically prevent up to 668 HIV infections among children annually. Cost-effectiveness estimates remained favorable over robust sensitivity analyses.ConclusionsAlthough more expensive than Option B, Option B+ substantially reduces MTCT in future pregnancies, increases both maternal and pediatric QALYs, and is a cost-effective use of limited resources in Ghana

Deciphering the epidemic synergy of herpes simplex virus type 2 (HSV-2) on human immunodeficiency virus type 1 (HIV-1) infection among women in sub-Saharan Africa

Background: Herpes Simplex Virus Type 2 (HSV-2) is highly prevalent in regions disproportionately affected by the human immunodeficiency virus (HIV-1) epidemic. The objective of our study was to identify the risk factors of HSV-2 and HIV-1 infections and to examine the association between the two infections. Methods: The study participants were recruited through a community based cross-sectional study that was conducted from November 2002 to March 2003 in the Moshi urban district of Northern Tanzania. A two-stage sampling design was used in recruiting the study participants. Information on socio-demographics, alcohol use, sexual behaviors, and STIs symptoms were obtained. Blood and urine samples were drawn for testing of HIV-1, HSV-2 and other STIs. Results: The prevalence of HSV-2 infection among all study participants was 43%. The prevalence rate of HSV-2 among the HIV-negative and HIV-positive women was 40% and 65%, respectively. We found 2.72 times odds of having HIV-1 in an HSV-2 positive woman than in an HSV-2 negative woman. Furthermore, HIV-1 and HSV-2 shared common high-risk sexual behavior factors such as early onset of sexual debut, and testing positive for other STIs. Conclusions: Our findings suggest that HSV-2 may be both a biological and risk-associated cofactor for HIV-1 acquisition. In resource-limited countries, where both infections are prevalent efforts at symptomatic and diagnostic screening and treatment of HSV-2 should be part of HIV-1 prevention programs

Comparative study of the persistence of anti-HIV activity of deoxynucleoside HIV reverse transcriptase inhibitors after removal from culture

<p>Abstract</p> <p>Background</p> <p>Most in vitro assays of drug potency may not adequately predict the performance in vivo. Methods to assess the persistence of antiviral activity of deoxynucleoside analogs, which require intracellular activation to the active metabolites that can persist in cells, will be important for designing dosages, combination regimens, and assessing treatment compliance. Using an HIV-IIIB/TZM-bl indicator cell culture system, we assessed the ability of an inhibitor to protect cells from infection and to delay viral rebound after removal of inhibitor from culture.</p> <p>Results</p> <p>The order of protection of cells from HIV-infection was 4'-Ed4T > LFD4C > DDI > D4T > 3TC > AZT > FTC > NVP. The fold-increase in EC₅₀to delay viral rebound was DDI < 4'-Ed4T < LFD4C < FTC < D4T < 3TC < NVP < AZT. The ranking of persistence of anti-HIV activity of the inhibitors based on the two-component assay was DDI > 4'-Ed4T > LFD4C > FTC = D4T > 3TC > NVP > AZT.</p> <p>Conclusion</p> <p>The persistence ranking was derived from assays based on measures of single viral replication-cycle and cumulative inhibition at multiple time-points. Therefore, a better indicator of the pharmacodynamic property of an inhibitor. The persistence of anti-HIV activity assay may complement in vitro potency assays to better predict in vivo performance of nucleoside analogs.</p

Time to and Predictors of CD4+ T-Lymphocytes Recovery in HIV-Infected Children Initiating Highly Active Antiretroviral Therapy in Ghana

Background. CD4+ T-lymphocyte monitoring is not routinely available in most resource-limited settings. We investigated predictors of time to CD4+ T-lymphocyte recovery in HIV-infected children on highly active antiretroviral (HAART) at Korle-Bu Teaching Hospital, Ghana. Methods. Time to CD4+ T-lymphocyte recovery was defined as achieving percent CD4+ T-lymphocytes of 25%. We used Cox proportional hazard models for identifying significant predictor variables. Results. Of the 233 children with complete CD4+ T-lymphocyte data, the mean age at HAART initiation was 5.5 (SD = 3.1) years. The median recovery time was 60 weeks (95% CL: 55–65). Evidence at baseline of severe suppression in CD4+ T-lymphocyte count adjusted for age, age at HAART initiation, gender, and having parents alive were statistically significant in predicting time to CD4+ T-lymphocyte recovery. Conclusions. A targeted approach based on predictors of CD4+ T-lymphocyte recovery can be a viable and cost-effective way of monitoring HAART in HIV-infected children in resource-limited settings

Comparison of Disk Diffusion and Etest Methods to Determine the Susceptibility of Staphylococcus aureus

Fusidic acid is a common therapy for staphylococcal infections in Saudi Arabia, but reports have suggested high rates of resistance among clinical isolates. Susceptibility testing of S. aureus to fusidic acid is further complicated by the lack of consensus on mean inhibitory concentrations (MIC) and disk diffusion cutoffs to determine resistance. The purpose of this study was to determine the correlation between disk diffusion and Etest determined MIC susceptibility results in clinical isolates of S. aureus from a large academic hospital in Riyadh, Saudi Arabia. Our data demonstrate excellent correlation between Etest determined MIC and disk diffusion susceptibility data, using either previously proposed zone sizes of ≥21 mm as susceptible and ≤18 mm as resistant or the EUCAST recommended zone size of ≤24 mm for resistance, in an area with relatively high rates of fusidic acid resistance

Viral load monitoring and antiretroviral treatment outcomes in a pediatric HIV cohort in Ghana

Background: HIV-infected children in sub-Saharan Africa may be at a high risk of staying on a failing first-line regimen and developing drug-resistance HIV variants due to lack of routine viral load monitoring. We investigated whether cumulative viral load, measured as viremia copy-years (VCY) could predict morbidity in a setting where viral load is not routinely monitored. Methods: This was a single-center prospective observational longitudinal study of HIV-infected children initiating antiretroviral therapy (ART) at the Pediatric HIV/AIDS Care program at Korle-Bu Teaching Hospital in Accra, Ghana. The main outcome was morbidity measured as frequency of hospitalizations, opportunistic infections, and outpatient sick visits. The main explanatory variable was viral load measured as VCY. Results: The study included 140 children who initiated ART between September 2009 and May 2013 and had at least 2 viral load measurements. There were 184 hospitalizations, with pneumonia being the most common cause (22.8 %). A total of 102 opportunistic infections was documented, with tuberculosis being the most common opportunistic infection (68 %). A total of 823 outpatient sick visits was documented, with upper respiratory infections (14.2 %) being the most common cause. Forty-four percent of our study participants had >4 log10 VCY. Children in this sub-cohort had a higher frequency of sick visits compared with those with 4 log10 VCY had been identified as treatment failure using WHO clinical and immunological treatment failure criteria. Conclusions: High level of cumulative viral load may translate to virological failure and subsequent increased all-cause morbidity. Our finding of potential utility of VCY in pediatrics warrants further investigations. VCY may be a good alternate to routine viral load measurement as its determination may be less frequent and could be personalized to save cost

Viral load monitoring and antiretroviral treatment outcomes in a pediatric HIV cohort in Ghana

Background: HIV-infected children in sub-Saharan Africa may be at a high risk of staying on a failing first-line regimen and developing drug-resistance HIV variants due to lack of routine viral load monitoring. We investigated whether cumulative viral load, measured as viremia copy-years (VCY) could predict morbidity in a setting where viral load is not routinely monitored. Methods: This was a single-center prospective observational longitudinal study of HIV-infected children initiating antiretroviral therapy (ART) at the Pediatric HIV/AIDS Care program at Korle-Bu Teaching Hospital in Accra, Ghana. The main outcome was morbidity measured as frequency of hospitalizations, opportunistic infections, and outpatient sick visits. The main explanatory variable was viral load measured as VCY. Results: The study included 140 children who initiated ART between September 2009 and May 2013 and had at least 2 viral load measurements. There were 184 hospitalizations, with pneumonia being the most common cause (22.8 %). A total of 102 opportunistic infections was documented, with tuberculosis being the most common opportunistic infection (68 %). A total of 823 outpatient sick visits was documented, with upper respiratory infections (14.2 %) being the most common cause. Forty-four percent of our study participants had >4 log10 VCY. Children in this sub-cohort had a higher frequency of sick visits compared with those with 4 log10 VCY had been identified as treatment failure using WHO clinical and immunological treatment failure criteria. Conclusions: High level of cumulative viral load may translate to virological failure and subsequent increased all-cause morbidity. Our finding of potential utility of VCY in pediatrics warrants further investigations. VCY may be a good alternate to routine viral load measurement as its determination may be less frequent and could be personalized to save cost

Transmission risk of respiratory viruses in natural and mechanical ventilation environments: implications for SARS-CoV-2 transmission in Africa.

Respiratory viruses can be transmitted through contact, droplet and airborne routes. Viruses that are not naturally airborne may be aerosolised during medical procedures and transmitted to healthcare workers. Most resource-limited healthcare settings lack complex air handling systems to filter air and create pressure gradients that are necessary for minimising viral transmission. This review explores the association between ventilation and the transmission of respiratory viruses like SAR-CoV-2. When used appropriately, both natural and mechanical ventilation can decrease the concentration of viral aerosols, thereby reducing transmission. Although mechanical ventilation systems are more efficient, installation and maintenance costs limit their use in resource-limited settings, whereas the prevailing climate conditions make natural ventilation less desirable. Cost-effective hybrid systems of natural and mechanical ventilation may overcome these limitations

Two Independent HIV Epidemics in Saint Petersburg, Russia Revealed by Molecular Epidemiology

The HIV epidemic in Russia, one of the world's fastest growing, has been concentrated mostly among people who inject drugs (PWID). We sought to explore the epidemiology of the epidemic in St. Petersburg by sampling from the highest risk groups of PWID and men who have sex with men (MSM) and use viral sequencing data to better understand the nature of the city's epidemic. Serological testing confirmed an HIV prevalence among PWID in excess of 40%. All but 1 of 110 PWID whose blood samples were tested for genetic diversity were infected by subtype A virus, specifically by the AFSU strain. The remaining person was infected with a CRF-06cpx recombinant. Analysis of pairwise genetic distance among all PWID studied revealed an average of 3.1% sequence divergence, suggesting clonal introduction of the AFSU strain and/or constraints on sequence divergence. The HIV prevalence was less than 10% among MSM. All 17 sequences from HIV-infected MSM were found to be a clade B virus with a much higher average sequence diversity of 15.7%. These findings suggest two independent epidemics with little overlap between the two highest at-risk populations, which will require different HIV prevention approaches