Access To Antiretroviral Therapy Research Articles

Time to First-Line ART Failure and Time to Second-Line ART Switch in the IeDEA Pediatric Cohort.

Globally, 49% of the estimated 1.8 million children living with HIV are accessing antiretroviral therapy (ART). There are limited data concerning long-term durability of first-line ART regimens and time to transition to second-line. Children initiating their first ART regimen between 2 and 14 years of age and enrolled in one of 208 sites in 30 Asia-Pacific and African countries participating in the Pediatric International Epidemiology Databases to Evaluate AIDS consortium were included in this analysis. Outcomes of interest were: first-line ART failure (clinical, immunologic, or virologic), change to second-line, and attrition (death or loss to program ). Cumulative incidence was computed for first-line failure and second-line initiation, with attrition as a competing event. In 27,031 children, median age at ART initiation was 6.7 years. Median baseline CD4% for children ≤5 years of age was 13.2% and CD4 count for those >5 years was 258 cells per microliter. Almost all (94.4%) initiated a nonnucleoside reverse transcriptase inhibitor; 5.3% a protease inhibitor, and 0.3% a triple nucleoside reverse transcriptase inhibitor-based regimen. At 1 year, 7.7% had failed and 14.4% had experienced attrition; by 5 years, the cumulative incidence was 25.9% and 29.4%, respectively. At 1 year after ART failure, 13.7% had transitioned to second-line and 11.2% had experienced attrition; by 5 years, the cumulative incidence was 31.6% and 25.9%, respectively. High rates of first-line failure and attrition were identified in children within 5 years after ART initiation. Of children meeting failure criteria, only one-third were transitioned to second-line ART within 5 years.

Cancer in adolescents and young adults living with HIV.

Adults living with HIV have an increased risk of malignancy yet there is little data for adolescents and young adults. We reviewed recently published cancer epidemiology, treatment, and outcome data for adolescents and young adults living with HIV (AYALHIV) aged 10 to less than 25 years between 2016 and 2017. AYALHIV are at increased risk of developing cancer compared to their uninfected peers. Kaposi sarcoma and non-Hodgkin lymphoma occur most frequently with variation by geographical region. Increased cancer risk is associated with HIV-related immunosuppression and coinfection with oncogenic viruses. Published data, particularly on posttreatment outcomes, remain limited and analyses are hampered by lack of data disaggregation by age and route of HIV transmission. Although data are sparse, the increased cancer risk for AYALHIV is the cause for concern and must be modified by improving global access and uptake of antiretroviral therapy, human papilloma virus (HPV) and hepatitis B virus (HBV) vaccination, screening for hepatitis B and C infection, and optimized cancer screening programs. Education aimed at reducing traditional modifiable cancer risk factors should be embedded within multidisciplinary services for AYALHIV.

Poverty as a barrier to antiretroviral therapy access for people living with HIV/AIDS in Kenya

Understanding barriers to access to essential health services is critical for devising effective strategies to improve access and align such strategies with national health and development policy objectives. However, while considerable empirical evidence exists on correlates of HIV prevalence and populations at risk of contracting HIV, there is very little such evidence on access to antiretroviral therapy. This paper addresses this gap through a cross-sectional analysis of coverage of antiretroviral therapy and its correlates across 47 counties in Kenya. It considers health-sector and social factors, and applying instrumental variables to address error-in-variables and reverse-causality issues regarding HIV prevalence. Poverty was the most robust and — statistically and substantially — significant determinant of treatment coverage. The gap in treatment coverage between the poorest and richest counties amounted to about 40 percentage points and has not narrowed between 2012 and 2015. Health sector capacities independently played a role and exacerbated the poverty gap. For Kenya, the results suggest that policies on expanding treatment access need to be differentiated across counties to greatest effect and to align the HIV/AIDS response with national health and social policy objectives. Regarding global HIV/AIDS policies, the findings suggest a need to recognise “people left behind” owing to socio-economic and specifically poverty-related barriers to access to services.

High Prevalence of Lipid Abnormalities and Insulin Resistance Among Antiretroviral Naïve HIV-infected Children in India.

As large numbers of children are accessing antiretroviral therapy (ART) in India, we evaluated the dietary intake, growth pattern and risk of metabolic complications like dyslipidemia and insulin resistance among ART-naïve HIV-infected children (CLHIV). CLHIV 2-12 years of age, at the time of initiating ART in Chennai and Bangalore, were assessed for their dietary intake, anthropometry, blood CD4 cell count, HIV-1 viral load, fasting serum lipids, glucose and insulin. Homeostatic model assessment-insulin resistance was derived. Three hundred and ninety CLHIV (mean age [SD]: 8 [3] yrs; median viral load: 141,000 [25,876-436,000] copies/mL) were started on non-nucleoside reverse transcriptase inhibitor-based ART. Perinatal infection was documented among 97%. Sixty percent of children were in stage 3 or 4 of World Health Organization clinical staging of HIV/AIDS. Food insecurity was seen in 40% of households. A total of 204 children (52.4%) were stunted and 224 (57.6%) were underweight. Stunting seemed to be more prevalent with increasing age (0-4 years: 48%; >9 years: 60%). Mean intakes of calories, iron, folate and calcium were significantly less than recommended dietary allowances across all age groups. Dyslipidemia, in terms of any abnormal triglycerides or total cholesterol or low-density lipoprotein cholesterol (excluding high-density lipoprotein cholesterol), was seen in approximately 40% of children; insulin resistance in 17%; and C-reactive protein in risk range of metabolic syndrome in 24% of children. In the background of high food insecurity and malnutrition, cardiometabolic abnormalities were seen in 20%-35% of ART-naïve CLHIV in India emphasizing close monitoring of these children for long-term cardiovascular morbidities after initiation of ART.

A Conditional Economic Incentive Fails to Improve Linkage to Care and Antiretroviral Therapy Initiation Among HIV-Positive Adults in Cape Town, South Africa.

Interventions to improve antiretroviral therapy (ART) access are urgently needed to maximize the multiple benefits from ART. This pilot study examined the effect of a conditional economic incentive on linkage to care and uptake of treatment following ART referral by a mobile health clinic. Between April 2015 and May 2016, 86 individuals (≥18 years old) referred for ART in a resource-limited setting were randomized (1:1) to a control group or to an incentive: R300 cash (∼$23, or 3.5 days minimum wage in the domestic worker sector), conditional upon starting ART within 3 months. Outcome data were obtained from clinic records. The incentive effects on linkage to care (first clinic visit within 3 months) and ART initiation (treatment uptake within 3 months) were assessed using logistic regression. Overall, 67% linked to care and 42% initiated ART within 3 months after referral. No significant differences were found between the incentive and non-incentive group in terms of linkage to care [adjusted odds ratio (aOR): 0.70, 95% confidence interval (CI): 0.26-1.91] and initiation of ART (aOR: 0.67, 95% CI: 0.26-1.78). Ordinary least-squares regression analysis showed that incentivized individuals linked to care in fewer days (-7.9, 95% CI: -18.09 to 2.26) and started treatment in fewer days (-7.3, 95% CI: -27.01 to 12.38), but neither result was statistically significant. Our findings demonstrate poor treatment uptake by both the intervention and control participants and further highlight the challenge in achieving universal early treatment access. Further research is required to understand how economic incentives, which have been shown to have many benefits, can be applied to improve linkage to HIV care and treatment.

Neurocognitive Impairment and Associated Genetic Aspects in HIV Infection.

HIV enters the central nervous system (CNS) early after infection. HIV-associated neurocognitive disorders (HAND) remain a serious complication of HIV infection despite available antiretroviral therapy (ART). Neurocognitive deficits observed in HAND are heterogeneous, suggesting a variability in individuals' susceptibility or resiliency to the detrimental CNS effects of HIV infection. This chapter reviews primary host genomic changes (immune-related genes, genes implicated in cognitive changes in primary neurodegenerative diseases), epigenetic mechanisms, and genetic interactions with ART implicated in HIV progression or HAND/neurocognitive complications of HIV. Limitations of the current findings include diversity of the HAND phenotype and limited replication of findings across cohorts. Strategies to improve the precision of future (epi)genetic studies of neurocognitive consequences of HIV infection are offered.

From policy to practice: exploring the implementation of antiretroviral therapy access and retention policies between 2013 and 2016 in six sub-Saharan African countries

BackgroundUnderstanding the implementation of 2013 World Health Organization (WHO) consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection at the facility level provides important lessons for the roll-out of future HIV policies.MethodsA national policy review was conducted in six sub-Saharan African countries to map the inclusion of the 2013 WHO HIV treatment recommendations. Twenty indicators of policy adoption were selected to measure ART access (n = 12) and retention (n = 8). Two sequential cross-sectional surveys were conducted in facilities between 2013/2015 (round 1) and 2015/2016 (round 2) from ten health and demographic surveillance sites in Kenya, Malawi, South Africa, Tanzania, Uganda and Zimbabwe. Using standardised questionnaires, facility managers were interviewed. Descriptive analyses were used to assess the change in the proportion of facilities that implemented these policy indicators between rounds.ResultsAlthough, expansion of ART access was explicitly stated in all countries’ policies, most lacked policies that enhanced retention. Overall, 145 facilities were included in both rounds. The proportion of facilities that initiated ART at CD4 counts of 500 or less cells/μL increased between round 1 and 2 from 12 to 68%, and facilities initiating patients on 2013 WHO recommended ART regimen increased from 42 to 87%. There were no changes in the proportion of facilities reporting stock-outs of first-line ART in the past year (18 to 11%) nor in the provision of three-month supply of ART (43 to 38%). None of the facilities provided community-based ART delivery.ConclusionThe increase in ART initiation CD4 threshold in most countries, and substantial improvements made in the provision of WHO recommended first-line ART regimens demonstrates that rapid adoption of WHO recommendations is possible. However, improved logistics and resources and/or changes in policy are required to further minimise ART stock-outs and allow lay cadres to dispense ART in the community. Increased efforts are needed to offer longer durations between clinic visits, a strategy purported to improve retention. These changes will be important as countries move to implement the revised 2015 WHO guidelines to initiate all HIV positive people onto ART regardless of their immune status.

Global, regional, and country-level coverage of interventions to prevent and manage HIV and hepatitis C among people who inject drugs: a systematic review.

SummaryBackgroundPeople who inject drugs (PWID) are a key population affected by the global HIV and hepatitis C virus (HCV) epidemics. HIV and HCV prevention interventions for PWID include needle and syringe programmes (NSP), opioid substitution therapy (OST), HIV counselling and testing, HIV antiretroviral therapy (ART), and condom distribution programmes. We aimed to produce country-level, regional, and global estimates of coverage of NSP, OST, HIV testing, ART, and condom programmes for PWID.MethodsWe completed searches of peer-reviewed (MEDLINE, Embase, and PsycINFO), internet, and grey literature databases, and disseminated data requests via social media and targeted emails to international experts. Programme and survey data on each of the named interventions were collected. Programme data were used to derive country-level estimates of the coverage of interventions in accordance with indicators defined by WHO, UNAIDS, and the UN Office on Drugs and Crime. Regional and global estimates of NSP, OST, and HIV testing coverage were also calculated. The protocol was registered on PROSPERO, number CRD42017056558.FindingsIn 2017, of 179 countries with evidence of injecting drug use, some level of NSP services were available in 93 countries, and there were 86 countries with evidence of OST implementation. Data to estimate NSP coverage were available for 57 countries, and for 60 countries to estimate OST coverage. Coverage varied widely between countries, but was most often low according to WHO indicators (<100 needle-syringes distributed per PWID per year; <20 OST recipients per PWID per year). Data on HIV testing were sparser than for NSP and OST, and very few data were available to estimate ART access among PWID living with HIV. Globally, we estimate that there are 33 (uncertainty interval [UI] 21–50) needle-syringes distributed via NSP per PWID annually, and 16 (10–24) OST recipients per 100 PWID. Less than 1% of PWID live in countries with high coverage of both NSP and OST (>200 needle-syringes distributed per PWID and >40 OST recipients per 100 PWID).InterpretationCoverage of HIV and HCV prevention interventions for PWID remains poor and is likely to be insufficient to effectively prevent HIV and HCV transmission. Scaling up of interventions for PWID remains a crucial priority for halting the HIV and HCV epidemics.FundingOpen Society Foundations, The Global Fund, WHO, UNAIDS, United Nations Office on Drugs and Crime, Australian National Drug and Alcohol Research Centre, University of New South Wales Sydney.

Prediction Of Costs On Antiretroviral Therapy In The Republic Of Belarus

The purpose of the pharmacoeconomic research was to determine ways to increase efficiency and accessibility of antiretroviral therapy (ART) in Belarus. We have used the following Methods: “naive” approach, trend extrapolation method and pharmacoeconomic modeling. Markov models have been built on the basis of the results of medicines clinical trials, cohort studies, epidemiological statistics on HIV infection in Belarus in 2012-2017. Nine antiretroviral therapy (ART) regimens have included a combination of 3 antiretroviral drugs of various classes: reverse transcriptase nucleoside inhibitors, reverse-transcriptase non-nucleoside inhibitors and protease inhibitors. 54 models have been obtained for nine ART regimens depending on the level of CD4+ cells/μl of blood (>500, 500-350, 350-200, 200-100, 100-50, 50-0). For each model we have defined a hypothetical number of years necessary to achieve a normal level of CD4+ cells of blood. We have calculated an average annual cost of therapy for one patient including: death, ART cessation, increase in CD4+ cells, constant level of CD4+ cells after ART initiation. Scheme-8 Zidovudine + Lamivudine + Nevirapine has the lowest cost of therapy: $183.19 for CD4+ >500 cells/μl, $193.05 for >350, $235.77 for <350. 7400 people with different levels of CD4+ received ART at the beginning of treatment in 2016 in Belarus and costs were $4135078.42. With "naive approach", the content of CD4+ >500 cells/μl and treatment according to Scheme-8 costs will be $1355606.00. Projected number of patients receiving ART in 2017 in Belarus will be 7871±363 (cubic trend, p<0.05). Total financial costs for getting CD4+ >500 cells/μl will be $1441888.49 ± 66497.97. We have determined the most effective and least expensive ART regimen. To reduce the cost of ART it is advisable to start the treatment process at the level of CD4+ >500 cells/μl. The saved money will allow to increase availability of ART in Belarus.

In Utero ART Exposure and Birth and Early Growth Outcomes Among HIV-Exposed Uninfected Infants Attending Immunization Services: Results From National PMTCT Surveillance, South Africa.

BackgroundDespite the recognized benefit of antiretroviral therapy (ART) for preventing and treating HIV, some studies have reported adverse birth outcomes with in utero ART exposure. We evaluated the effect of infant in utero HIV and ART exposure on preterm delivery (PTD), low birth weight (LBW), small for gestational age (SGA), and underweight for age (UFA) at 6 weeks.MethodsWe surveyed 6179 HIV-unexposed-uninfected (HUU) and 2599 HIV-exposed-uninfected (HEU) infants. HEU infants were stratified into 3 groups: ART, Zidovudine alone, and no antiretrovirals (None). The ART group was further stratified to explore pre- or postconception exposure. Multivariable logistic regression evaluated effects of HIV and ARV exposure on the outcomes.ResultsWe found higher odds of PTD, LBW, SGA, and UFA in HEU than HUU infants. HEU in the None group (adjusted odds ratio [AOR], 1.9; 95% confidence interval [CI], 1.2–3.0) or those whose mothers initiated ART preconception (AOR, 1.7; 95% CI, 1.1–2.5) had almost twice the odds of PTD than infants whose mothers started ART postconception, but no increased odds for other outcomes.ConclusionsThere was an association between preconception ART and PTD. As ART access increases, pregnancy registers or similar surveillance should be in place to monitor outcomes to inform future policy.

Knowledge of HIV-related disabilities and challenges in accessing care: Qualitative research from Zimbabwe.

IntroductionWhile the rapid expansion in antiretroviral therapy access in low and middle income countries has resulted in dramatic declines in mortality rates, many people living with HIV face new or worsening experiences of disability. As nearly 1 in 20 adults are living with HIV in sub-Saharan Africa–many of whom are likely to develop disabling sequelae from long-term infection, co-morbidities and side effects of their treatment–understanding the availability and accessibility of services to address HIV-related disabilities is of vital importance. The aim of this study thus is to explore knowledge of HIV-related disabilities amongst stakeholders working in the fields of HIV and disability and factors impacting uptake and provision of interventions for preventing, treating or managing HIV-related disabilities.MethodsIn-depth, semi-structured interviews were conducted with ten stakeholders based in Harare, Zimbabwe, who were working in the fields of either disability or HIV. Stakeholders were identified through a priori stakeholder analysis. Thematic Analysis, complemented by constant comparison as described in Grounded Theory, was used to analyse findings.ResultsAll key informants reported some level of knowledge of HIV-related disability, mostly from observations made in their line of work. However, they reported no interventions or policies were in place specifically to address HIV-related disability. While referrals between HIV and rehabilitation providers were not uncommon, no formal mechanisms had been established for collaborating on prevention, identification and management. Additional barriers to accessing and providing services to address HIV-related disabilities included: the availability of resources, including trained professionals, supplies and equipment in both the HIV and rehabilitation sectors; lack of disability-inclusive adaptations, particularly in HIV services; heavy centralization of available services in urban areas, without accessible, affordable transportation links; and attitudes and understanding among service providers and people living with HIV-related disabilities.ConclusionsAs people living with HIV are surviving longer, HIV-related disabilities will become a major source of disability globally, particularly in sub-Saharan Africa where infection is endemic. Preventing, treating and managing HIV-related disabilities must become a key component of both HIV response efforts and rehabilitation strategies.

HIV status and treatment influence on fertility desires among women newly becoming eligible for antiretroviral therapy in western Kenya: insights from a qualitative study

BackgroundFactors influencing fertility desires among HIV-infected individuals remain poorly understood. With new recommendations for universal HIV treatment and increasing antiretroviral therapy (ART) access, we sought to evaluate how access to early ART influences fertility desires among HIV-infected ART-naïve women.MethodsSemi-structured in-depth interviews were conducted with a select subgroup of 20 HIV-infected ART-naïve women attending one of 13 HIV facilities in western Kenya between July and August 2014 who would soon newly become eligible to initiate ART based on the latest national policy recommendations. The interviews covered four major themes: 1) definitions of family and children’s role in community; 2) personal, interpersonal, institutional, and societal factors influencing fertility desires; 3) influence of HIV-positive status on fertility desires; and 4) influence of future ART initiation on fertility desires. An iterative process of reading transcripts, applying inductive codes, and comparing and contrasting codes was used to identify convergent and divergent themes.ResultsThe women indicated their HIV-positive status did influence—largely negatively—their fertility desires. Furthermore, initiating ART and anticipating improved health status did not necessarily translate to increased fertility desires. Instead, individual factors, such as age, parity, current health status, financial resources and number of surviving or HIV-infected children, played a crucial role in decisions about future fertility. In addition, societal influences, such as community norms and health providers’ expectations of their fertility desires, played an equally important role in determining fertility desires.ConclusionsInitiating ART may not be the leading factor influencing fertility desires among previously ART-naïve HIV-infected women. Instead, individual and societal factors appear to be the major determinants of fertility desires among these women.

Low levels of viral suppression among refugees and host nationals accessing antiretroviral therapy in a Kenyan refugee camp

BackgroundRefugees and host nationals who accessed antiretroviral therapy (ART) in a remote refugee camp in Kakuma, Kenya (2011–2013) were compared on outcome measures that included viral suppression and adherence to ART.MethodsThis study used a repeated cross-sectional design (Round One and Round Two). All adults (≥18 years) receiving care from the refugee camp clinic and taking antiretroviral therapy (ART) for ≥30 days were invited to participate. Adherence was measured by self-report and monthly pharmacy refills. Whole blood was measured on dried blood spots. HIV-1 RNA was quantified and treatment failures were submitted for drug resistance testing. A remedial intervention was implemented in response to baseline testing. The primary outcome was viral load <5000 copies/mL. The two study rounds took place in 2011-2013.ResultsAmong eligible adults, 86% (73/85) of refugees and 84% (86/102) of Kenyan host nationals participated in the Round One survey; 60% (44/73) and 58% (50/86) of Round One participants were recruited for Round Two follow-up viral load testing. In Round One, refugees were older than host nationals (median age 36 years, interquartile range, IQR 31, 41 vs 32 years, IQR 27, 38); the groups had similar time on ART (median 147 weeks, IQR 38, 64 vs 139 weeks, IQR 39, 225). There was weak evidence for a difference in the proportion of refugees and host nationals who were virologically suppressed (<5000 copies/mL) after 25 weeks on ART (58% vs 43%, p = 0.10) and no difference in the proportions suppressed at Round Two (74% vs 70%, p = 0.66). Mean adherence within each group in Round One was similar. Refugee status was not associated with viral suppression in multivariable analysis (adjusted odds ratio: 1.69, 95% CI 0.79, 3.57; p = 0.17). Among those not suppressed at either timepoint, 69% (9/13) exhibited resistance mutations.ConclusionsVirologic outcomes among refugees and host nationals were similar but unacceptably low. Slight improvements were observed after a remedial intervention. Virologic monitoring was important for identifying an underperforming ART program in a remote facility that serves refugees alongside host nationals. This work highlights the importance of careful laboratory monitoring of vulnerable populations accessing ART in remote settings.

Predictors of loss to follow-up among patients on ART at a rural hospital in KwaZulu-Natal, South Africa.

IntroductionImproved HIV outcomes as a result of expanded antiretroviral therapy (ART) access is threatened by increasing rates of loss to follow up (LTFU) among those on ART, largely reported in urban populations. Some reports suggest that LTFU rates are overestimated due to patient movement to other facilities and inadequate medical records.Study objectiveTo define the proportion disengaging from HIV care as well as the characteristics of those LTFU in order to design and implement appropriate interventions to increase retention.MethodsWe performed a retrospective review of patients who discontinued ART at a central hospital ART clinic in rural South Africa and compared with patients receiving care at the 15 primary health clinics (PHCs) to determine the true proportion of those who were LTFU. We also compared those who discontinued ART with those who did not at the central hospital ART clinic to determine predictors of loss to follow up.ResultsAmong 3242 patients on ART, 820 were originally marked as LTFU. Among all patients, 272 (8.4%) were found at a clinic on treatment, 56 (1.7%) were found at a clinic from which they had since discontinued treatment, and 10 (0.3%) returned to care between June and July 2016, leaving 475 (14.7%) unaccounted for and thus categorized as ‘true’ LTFU. Factors found to be associated with discontinuation include being male, age 18–35, having a CD4 count under 200 cells/μL, and being on ART for under six months.ConclusionsYoung men with low CD4 counts early after ART initiation are at highest risk of ART disengagement in this rural South African HIV clinic. Novel interventions targeting this group are needed to improve retention in care.

Rubella/SIV vectors for immunotherapy of SIV infection in rhesus macaques

Abstract Currently available anti-retroviral therapy (ART) can fully suppress viremia after SIV infection in macaques, but the drugs do not cure infection. When ART drugs are withdrawn, the virus rebounds vigorously. Apparently, ART cannot control or eliminate viral reservoirs. We postulate that early ART, combined with induction of strong T-cell immunity via live viral vectors, can achieve a functional cure by reducing or eliminating long-lived viral reservoirs. This could be detected as lack of viral rebound when ART is stopped. We have developed the rubella vaccine strain (RA27/3)as a live attenuated viral vector that was safe and highly immunogenic in rhesus macaques. Rubella vectors-expressing SIV Gag replicated vigorously in vivo while eliciting potent T cellimmunity to gag. The vectors alsoelicited anti-Gag antibodies that were equal to SIV infection, durable for &amp;gt;1 year, and were boosted by re-exposure to the vector. We are testing immunotherapy in a three stage experiment: 1st stage, SIV infection followed by starting ART on day 3; 2nd, Immunizing with SIV/Gag vectors while on ART; 3rd Stopping ART and measuring viral rebound. So far, we have shown complete viral suppression while on ART and a good immune response to the rubella vector and to the gag insert. Pending viral loads will indicate whether all control animals were infected by SIV, and any reduction or delay in viral rebound due to immunotherapy effects on the viral reservoir. The results in primate models may predict the effect of immune therapy on recent HIV infection of humans. This approach could be ideal for treating HIV infection in infants, since the viral reservoir is small, and the immune system is still intact and capable of responding to the rubella/gagvector.

Maternal Binding and Neutralizing IgG Responses Targeting the C-Terminal Region of the V3 Loop Are Predictive of Reduced Peripartum HIV-1 Transmission Risk.

The development of an effective maternal HIV-1 vaccine that could synergize with antiretroviral therapy (ART) to eliminate pediatric HIV-1 infection will require the characterization of maternal immune responses capable of blocking transmission of autologous HIV to the infant. We previously determined that maternal plasma antibody binding to linear epitopes within the variable loop 3 (V3) region of HIV envelope (Env) and neutralizing responses against easy-to-neutralize tier 1 viruses were associated with reduced risk of peripartum HIV infection in the historic U.S. Woman and Infant Transmission Study (WITS) cohort. Here, we defined the fine specificity and function of the potentially protective maternal V3-specific IgG antibodies associated with reduced peripartum HIV transmission risk in this cohort. The V3-specific IgG binding that predicted low risk of mother-to-child-transmission (MTCT) was dependent on the C-terminal flank of the V3 crown and particularly on amino acid position 317, a residue that has also been associated with breakthrough transmission in the RV144 vaccine trial. Remarkably, the fine specificity of potentially protective maternal plasma V3-specific tier 1 virus-neutralizing responses was dependent on the same region in the V3 loop. Our findings suggest that MTCT risk is associated with neutralizing maternal IgG that targets amino acid residues in the C-terminal region of the V3 loop crown, suggesting the importance of the region in immunogen design for maternal vaccines to prevent MTCT.IMPORTANCE Efforts to curb HIV-1 transmission in pediatric populations by antiretroviral therapy (ART) have been highly successful in both developed and developing countries. However, more than 150,000 infants continue to be infected each year, likely due to a combination of late maternal HIV diagnosis, lack of ART access or adherence, and drug-resistant viral strains. Defining the fine specificity of maternal humoral responses that partially protect against MTCT of HIV is required to inform the development of a maternal HIV vaccine that will enhance these responses during pregnancy. In this study, we identified amino acid residues targeted by potentially protective maternal V3-specific IgG binding and neutralizing responses, localizing the potentially protective response in the C-terminal region of the V3 loop crown. Our findings have important implications for the design of maternal vaccination strategies that could synergize with ART during pregnancy to achieve the elimination of pediatric HIV infections.

High mortality among tuberculosis patients on treatment in Nigeria: a retrospective cohort study

BackgroundTuberculosis (TB) remains a leading cause of death in much of sub-Saharan Africa despite available effective treatment. Prompt initiation of TB treatment and access to antiretroviral therapy (ART) remains vital to the success of TB control. We assessed time to mortality after treatment onset using data from a large treatment centre in Nigeria.MethodsWe analysed a retrospective cohort of TB patients that commenced treatment between January 2010 and December 2014 in Aminu Kano Teaching Hospital. We estimated mortality rates per person-months at risk (pm). Cox proportional hazards model was used to determine risk factors for mortality.ResultsAmong 1,424 patients with a median age of 36.6 years, 237 patients (16.6%) died after commencing TB treatment giving a mortality rate of 3.68 per 100 pm of treatment in this cohort. Most deaths occurred soon after treatment onset with a mortality rate of 37.6 per 100 pm in the 1st week of treatment. Risk factors for death were being HIV-positive but not on anti-retroviral treatment (ART) (aHR 1.39(1 · 04–1 · 85)), residence outside the city (aHR 3 · 18(2.28–4.45)), previous TB treatment (aHR 3.48(2.54–4.77)), no microbiological confirmation (aHR 4.96(2.69–9.17)), having both pulmonary and extra-pulmonary TB (aHR 1.45(1.03–2.02), and referral from a non-programme linked clinic/centre (aHR 3.02(2.01–4.53)).ConclusionsWe attribute early deaths in this relatively young cohort to delay in diagnosis and treatment of TB, inadequate treatment of drug-resistant TB, and poor ART access. Considerable expansion and improvement in quality of diagnosis and treatment services for TB and HIV are needed to achieve the sustainable development goal of reducing TB deaths by 95% by 2035.

REVIEW OF HIV IN SUB-SAHARAN AFRICA: CURRENT SITUATION, OPPORTUNITIES AND CHALLENGES

UNAIDS estimates that in 2015, 19 million (17.7–20.5 million) and 6.5 million (5.3–7.8 million) people were living with HIV in Eastern and Southern Africa (ESA) and Western and Central Africa...

Clinical characteristics of pediatric HIV-1 patients treated with first-line antiretroviral therapy in Vietnam: a nested case-control study.

Over the past decades, Vietnam has made great strides in reducing the rate of mortality in HIV-related deaths, due to increased access of antiretroviral therapy (ART); however, given the significantly high level of treatment failure (TF), it is essential to identify markers that describe the failure of ART in HIV-1 infected children. A nested case-control study was conducted with clinical data collected from 101 HIV-infected children [26 TF and 75 treatment success (TS)] at National Hospital of Pediatrics, Vietnam (2008-2012). The results showed that certain factors including height, weight, vaccination with Hepatitis B, and platelet were significantly different between TF and TS before starting the treatment. In addition, age to start the treatment, CD4 percentage, and opportunistic infection were found to significantly predict treatment outcome most frequently, implying the importance of clinical markers in the treatment response by Cox regression analysis. There is an inherent complexity within clinical markers that is challenging to determine HIV-pediatric failure and further research is needed to build a complete picture to guide clinical, evidence-based practice.

Bronchiectasis and other chronic lung diseases in adolescents living with HIV.

The incidence of pulmonary infections has declined dramatically with improved access to antiretroviral therapy (ART) and cotrimoxazole prophylaxis, but chronic lung disease (CLD) is an increasingly recognized but poorly understood complication in adolescents with perinatally acquired HIV. There is a high prevalence of chronic respiratory symptoms, abnormal spirometry and chest radiographic abnormalities among HIV-infected adolescents in sub-Saharan Africa, wherein 90% of the world's HIV-infected children live. The incidence of lymphocytic interstitial pneumonitis, the most common cause of CLD in the pre-ART era, has declined with increased ART access. Small airways disease, particularly constrictive obliterative bronchiolitis and bronchiectasis, are emerging as leading causes of CLD among HIV-infected adolescents in low-income and middle-income countries. Asthma may be more common in high-income settings. Likely risk factors for CLD include recurrent pulmonary infections, air pollution, HIV-related immune dysfunction, and untreated HIV infection, particularly during critical stages of lung development. Globally, the importance of HIV-associated CLD as a cause of morbidity and mortality is increasing, especially as survival has improved dramatically with ART and growing numbers of children living with HIV enter adolescence. Further research is urgently needed to elucidate the natural history and pathogenesis of CLD, and to determine optimal screening, diagnostic and treatment strategies.