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Open Forum Infectious Diseases May 2022The late recognition of virologic failure (VF) places persons with HIV in Sub-Saharan Africa at risk for HIV transmission, disease progression, and death. We conducted a...
BACKGROUND
The late recognition of virologic failure (VF) places persons with HIV in Sub-Saharan Africa at risk for HIV transmission, disease progression, and death. We conducted a systematic review and meta-analysis to determine if the recognition and response to VF in the region has improved.
METHODS
We searched for studies reporting CD4 count at confirmed VF or at switch to second-line antiretroviral therapy (ART). Using a random-effects metaregression model, we analyzed temporal trends in CD4 count at VF-or at second-line ART switch-over time. We also explored temporal trends in delay between VF and switch to second-line ART.
RESULTS
We identified 26 studies enrolling patients with VF and 10 enrolling patients at second-line ART switch. For studies that enrolled patients at VF, pooled mean CD4 cell count at failure was 187 cells/mm (95% CI, 111 to 263). There was no significant change in CD4 count at confirmed failure over time (+4 cells/year; 95% CI, -7 to 15). Among studies that enrolled patients at second-line switch, the pooled mean CD4 count was 108 cells/mm (95% CI, 63 to 154). CD4 count at switch increased slightly over time (+10 CD4 cells/year; 95% CI, 2 to 19). During the same period, the mean delay between confirmation of VF and switch was 530 days, with no significant decline over time (-14 days/year; 95% CI, -58 to 52).
CONCLUSIONS
VF in Africa remains an event recognized late in HIV infection, a problem compounded by ongoing delays between VF and second-line switch.
PubMed: 35434173
DOI: 10.1093/ofid/ofac121 -
Tropical Medicine & International... Jul 2017Home-based HIV counselling and testing (HBHCT) has the potential to increase HIV testing uptake in sub-Saharan Africa (SSA), but data on linkage to HIV care after HBHCT... (Review)
Review
BACKGROUND
Home-based HIV counselling and testing (HBHCT) has the potential to increase HIV testing uptake in sub-Saharan Africa (SSA), but data on linkage to HIV care after HBHCT are scarce. We conducted a systematic review of linkage to care after HBHCT in SSA.
METHODS
Five databases were searched for studies published between 1st January 2000 and 19th August 2016 that reported on linkage to care among adults newly identified with HIV infection through HBHCT. Eligible studies were reviewed, assessed for risk of bias and findings summarised using the PRISMA guidelines.
RESULTS
A total of 14 studies from six countries met the eligibility criteria; nine used specific strategies (point-of-care CD4 count testing, follow-up counselling, provision of transport funds to clinic and counsellor facilitation of HIV clinic visit) in addition to routine referral to facilitate linkage to care. Time intervals for ascertaining linkage ranged from 1 week to 12 months post-HBHCT. Linkage ranged from 8.2% [95% confidence interval (CI), 6.8-9.8%] to 99.1% (95% CI, 96.9-99.9%). Linkage was generally lower (<33%) if HBHCT was followed by referral only, and higher (>80%) if additional strategies were used. Only one study assessed linkage by means of a randomised trial. Five studies had data on cotrimoxazole (CTX) prophylaxis and 12 on ART eligibility and initiation. CTX uptake among those eligible ranged from 0% to 100%. The proportion of persons eligible for ART ranged from 16.5% (95% CI, 12.1-21.8) to 77.8% (95% CI, 40.0-97.2). ART initiation among those eligible ranged from 14.3% (95% CI, 0.36-57.9%) to 94.9% (95% CI, 91.3-97.4%). Additional linkage strategies, whilst seeming to increase linkage, were not associated with higher uptake of CTX and/or ART. Most of the studies were susceptible to risk of outcome ascertainment bias. A pooled analysis was not performed because of heterogeneity across studies with regard to design, setting and the key variable definitions.
CONCLUSION
Only few studies from SSA investigated linkage to care among adults newly diagnosed with HIV through HBHCT. Linkage was often low after routine referral but higher if additional interventions were used to facilitate it. The effectiveness of linkage strategies should be confirmed through randomised controlled trials.
Topics: Africa South of the Sahara; Anti-Bacterial Agents; Anti-Retroviral Agents; Counseling; HIV Infections; Home Care Services; Humans; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 28449385
DOI: 10.1111/tmi.12888 -
Frontiers in Immunology 2021Despite the discovery that the human immunodeficiency virus 1 (HIV-1) is the pathogen of acquired immunodeficiency syndrome (AIDS) in 1983, there is still no effective...
Despite the discovery that the human immunodeficiency virus 1 (HIV-1) is the pathogen of acquired immunodeficiency syndrome (AIDS) in 1983, there is still no effective anti-HIV-1 vaccine. The major obstacle to the development of HIV-1 vaccine is the extreme diversity of viral genome sequences. Nonetheless, a number of broadly neutralizing antibodies (bNAbs) against HIV-1 have been made and identified in this area. Novel strategies based on using these bNAbs as an efficacious preventive and/or therapeutic intervention have been applied in clinical. In this review, we summarize the recent development of bNAbs and its application in HIV-1 acquisition prevention as well as discuss the innovative approaches being used to try to convey protection within individuals at risk and being treated for HIV-1 infection.
Topics: AIDS Vaccines; Animals; Antibody Specificity; Broadly Neutralizing Antibodies; Gene Transfer Techniques; Genes, env; Genetic Therapy; Genetic Variation; HIV Antibodies; HIV Infections; HIV-1; Humans; Immunity, Humoral; Immunization, Passive; Models, Immunological; Vaccine Development; env Gene Products, Human Immunodeficiency Virus
PubMed: 34354709
DOI: 10.3389/fimmu.2021.697683 -
European Journal of Medical Research Feb 2022Immunocompromised (IC) patients are at higher risk of severe SARS-CoV-2 infection, morbidity, and mortality compared to the general population. They should be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Immunocompromised (IC) patients are at higher risk of severe SARS-CoV-2 infection, morbidity, and mortality compared to the general population. They should be prioritized for primary prevention through vaccination. This study aimed to evaluate the efficacy of COVID-19 mRNA vaccines in IC patients through a systematic review and meta-analysis approach.
METHOD
PubMed-MEDLINE, Scopus, and Web of Science were searched for original articles reporting the immunogenicity of two doses of mRNA COVID-19 vaccines in adult patients with IC condition between June 1, 2020 and September 1, 2021. Meta-analysis was performed using either random or fixed effect according to the heterogeneity of the studies. Subgroup analysis was performed to identify potential sources of heterogeneity.
RESULTS
A total of 26 studies on 3207 IC patients and 1726 healthy individuals were included. The risk of seroconversion in IC patients was 48% lower than those in controls (RR = 0.52 [0.42, 0.65]). IC patients with autoimmune conditions were 54%, and patients with malignancy were 42% more likely to have positive seroconversion than transplant recipients (P < 0.01). Subgroup meta-analysis based on the type of malignancy, revealed significantly higher proportion of positive seroconversion in solid organ compared to hematologic malignancies (RR = 0.88 [0.85, 0.92] vs. 0.61 [0.44, 0.86], P = 0.03). Subgroup meta-analysis based on type of transplantation (kidney vs. others) showed no statistically significant between-group difference of seroconversion (P = 0.55).
CONCLUSIONS
IC patients, especially transplant recipients, developed lower immunogenicity with two-dose of COVID-19 mRNA vaccines. Among patients with IC, those with autoimmune conditions and solid organ malignancies are mostly benefited from COVID-19 vaccination. Findings from this meta-analysis could aid healthcare policymakers in making decisions regarding the importance of the booster dose or more strict personal protections in the IC patients.
Topics: Autoimmune Diseases; COVID-19 Vaccines; Case-Control Studies; Humans; Immunocompromised Host; Neoplasms; Organ Transplantation; Vaccines, Synthetic; mRNA Vaccines
PubMed: 35151362
DOI: 10.1186/s40001-022-00648-5 -
The Lancet Regional Health. Western... Jul 2021Herpes simplex virus type 2 (HSV-2) infection is a prevalent sexually transmitted infection worldwide. This systematic review was conducted to characterize HSV-2...
BACKGROUND
Herpes simplex virus type 2 (HSV-2) infection is a prevalent sexually transmitted infection worldwide. This systematic review was conducted to characterize HSV-2 epidemiology in Asia, including the World Health Organization regions of Southeast Asia and the Western Pacific.
METHODS
Cochrane and PRISMA guidelines were followed to systematically review and report findings. Pooled mean seroprevalence and proportions of HSV-2 isolated in genital ulcer disease (GUD) and in genital herpes were calculated using random-effects meta-analyses. Meta-regressions were also conducted. Quality assessment was performed.
FINDINGS
HSV-2 measures extracted from 173 publications included 15 seroconversion rates, 11 seroincidence rates, 272 overall seroprevalence measures (678 stratified), 14 proportions of HSV-2 isolation in GUD (15 stratified), and 27 proportions of HSV-2 isolation in genital herpes (36 stratified). Pooled mean seroprevalence was 12.1% (95% confidence interval (CI): 11.0-13.2%) among general populations, 23.6% (95% CI: 20.9-26.3%) among men who have sex with men and transgender people, 46.0% (95% CI: 39.2-52.9%) among HIV-positive individuals and individuals in HIV-discordant couples, and 62.2% (95% CI: 58.9-65.6%) among female sex workers. Among general populations, pooled mean seroprevalence increased gradually from 4.7% (95% CI: 3.3-6.3%) in <20-year-old individuals to 26.6% (95% CI: 19.2-34.7%) in >60-year-old individuals. Compared to women and across all populations, men had 0.60-fold (95% CI: 54.0-67.0) lower seroprevalence, that is women had 70% higher seroprevalence. Seroprevalence declined by 0.98-fold (95% CI: 0.97-0.99) per year, that is a 2% decline per year in the last three decades. Pooled mean proportions of HSV-2 isolation in GUD and in genital herpes were 48.2% (95% CI: 34.9-61.6%) and 75.9% (95% CI: 68.3-82.8%), respectively.
INTERPRETATION
Over 1 in 10 individuals is infected with HSV-2, but seroprevalence is declining. HSV-2 accounts for half of GUD cases and three-quarters of genital herpes cases. These findings support the need for an HSV-2 vaccine and universal access to sexual and reproductive health services.
FUNDING
This work was supported by the Qatar National Research Fund [NPRP 9-040-3-008] and by pilot funding from the Biomedical Research Program at Weill Cornell Medicine in Qatar.
PubMed: 34527970
DOI: 10.1016/j.lanwpc.2021.100176 -
PharmacoEconomics - Open Mar 2017The aim of this paper was to review and compare HIV vaccine cost-effectiveness analyses and describe the effects of uncertainty in model, methodology, and...
OBJECTIVE
The aim of this paper was to review and compare HIV vaccine cost-effectiveness analyses and describe the effects of uncertainty in model, methodology, and parameterization.
METHODS
We systematically searched MEDLINE (1985 through May 2016), EMBASE, the Tufts CEA Registry, and reference lists of articles following Cochrane guidelines and PRISMA reporting. Eligibility criteria included peer-reviewed manuscripts with economic models estimating cost-effectiveness of preventative HIV vaccines. Two reviewers independently assessed study quality and extracted data on model assumptions, characteristics, input parameters, and outcomes.
RESULTS
The search yielded 71 studies, of which 11 met criteria for inclusion. Populations included low-income (n=7), middle-income (n=4), and high-income countries (n=2). Model structure varied including decision tree (n=1), Markov (n=5), compartmental (n=4), and microsimulation (n=1). Most measured outcomes in quality adjusted life-years (QALYs) gained (n=6) while others used unadjusted (n=3) or disability adjusted life-years (n=2). HIV vaccine cost ranged from $1.54 -$75 USD in low-income countries, $55-$100 in middle-income countries, and $500-$1,000 in the United States. Base case ICERs ranged from dominant (cost-offsetting) to $91,000 per QALY gained.
CONCLUSION
Most models predicted HIV vaccines would be cost-effective. Model assumptions about vaccine price, HIV treatment costs, epidemic context, and willingness to pay influenced results more consistently than assumptions on HIV transmission dynamics.
PubMed: 28367539
DOI: 10.1007/s41669-016-0009-9 -
Current HIV/AIDS Reports Apr 2021The relationship between antiretroviral therapy (ART) and cancer treatment outcomes among people living with HIV (PLWH) in low- and middle-income countries (LMICs) is... (Review)
Review
PURPOSE OF REVIEW
The relationship between antiretroviral therapy (ART) and cancer treatment outcomes among people living with HIV (PLWH) in low- and middle-income countries (LMICs) is complex and poorly understood for many cancers. We aimed to summarize existing evidence from LMICs regarding the benefit of ART on cancer treatment-related outcomes.
RECENT FINDINGS
We included twelve observational studies that reported associations between ART status and cancer treatment outcomes among HIV-positive patients in LMICs. Most confirmed ART was associated with improved cancer treatment outcomes. Heterogeneity in cancers under study, outcome measurement, categorization of ART status, and reporting of HIV-related immune function made formal comparison between studies untenable. Where evaluated, ART generally has a positive effect on cancer outcomes in people with HIV in LMICs. However, there remains a substantial gap in the literature regarding the impact of ART on treatment outcomes for most cancer types. Future research should focus on the optimal timing and integration of ART and cancer treatment for PLWH with strategies applicable to constrained-resource settings.
Topics: Anti-HIV Agents; Developing Countries; HIV Infections; Humans; Neoplasms; Poverty; Treatment Outcome
PubMed: 33528741
DOI: 10.1007/s11904-021-00542-5 -
ELife Oct 2022Adolescent girls and young women (AGYW) are at high risk of sexually transmitted infections (STIs). It is unknown whether beginning to have sexual intercourse results in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adolescent girls and young women (AGYW) are at high risk of sexually transmitted infections (STIs). It is unknown whether beginning to have sexual intercourse results in changes to immune mediators in the cervicovaginal tract that contribute to this risk.
METHODS
We collected cervicovaginal lavages from Kenyan AGYW in the months before and after first penile-vaginal sexual intercourse and measured the concentrations of 20 immune mediators. We compared concentrations pre- and post-first sex using mixed effect models. We additionally performed a systematic review to identify similar studies and combined them with our results by meta-analysis of individual participant data.
RESULTS
We included 180 samples from 95 AGYW, with 44% providing only pre-first sex samples, 35% matched pre and post, and 21% only post. We consistently detected 19/20 immune mediators, all of which increased post-first sex (p<0.05 for 13/19; Holm-Bonferroni-adjusted p<0.05 for IL-1β, IL-2, and CXCL8). Effects remained similar after excluding samples with STIs and high Nugent scores. Concentrations increased cumulatively over time after date of first sex, with an estimated doubling time of about 5 months.Our systematic review identified two eligible studies, one of 93 Belgian participants, and the other of 18 American participants. Nine immune mediators were measured in at least two-thirds of studies. Meta-analysis confirmed higher levels post-first sex for 8/9 immune mediators (p<0.05 for six mediators, most prominently IL-1α, IL-1β, and CXCL8).
CONCLUSIONS
Cervicovaginal immune mediator concentrations were higher in women who reported that they started sexual activity. Results were consistent across three studies conducted on three different continents.
FUNDING
This research was funded by R01 HD091996-01 (ACR), by P01 AI 030731-25 (Project 1) (AW), R01 AI116292 (FH), R03 AI154366 (FH) and by the Center for AIDS Research (CFAR) of the University of Washington/Fred Hutchinson Cancer Research Center AI027757.
Topics: Adolescent; Humans; Female; Coitus; Prospective Studies; Kenya; Interleukin-2; Sexually Transmitted Diseases; Sexual Behavior; Immunologic Factors; HIV Infections
PubMed: 36281966
DOI: 10.7554/eLife.78565 -
AIDS (London, England) Mar 2018To review the main factors influencing the costs of nondaily oral preexposure prophylaxis (PrEP) with tenofovir (±emtricitabine). To estimate the cost reductions...
OBJECTIVES
To review the main factors influencing the costs of nondaily oral preexposure prophylaxis (PrEP) with tenofovir (±emtricitabine). To estimate the cost reductions possible with nondaily PrEP compared with daily PrEP for different populations (MSM and heterosexual populations).
DESIGN
Systematic review and data triangulation.
METHODS
We estimated the required number of tablets/person/week for dosing regimens used in the HPTN 067/ADAPT (daily/time-driven/event-driven) and IPERGAY (on-demand) trials for different patterns of sexual intercourse. Using trial data, and behavioural and cost data obtained through systematic literature reviews, we estimated cost savings resulting from tablet reductions for nondaily versus daily oral PrEP, assuming 100% adherence.
RESULTS
Among different populations being prioritized for PrEP, the median reported number of days of sexual activity varied between 0 and 2 days/week (0-1.5 days/week for MSM, 1-2 days/week for heterosexual populations). With 100% adherence and two or fewer sex-days/week, HPTN 067/ADAPT nondaily regimens reduced the number of tablets/week by more than 40% compared with daily PrEP. PrEP program costs were reduced the most in settings with high drug costs, for example, by 66-69% with event-driven PrEP for French/US populations reporting on average one sex-day/week.
CONCLUSION
Nondaily oral PrEP could lower costs substantially (>50%) compared with daily PrEP, particularly in high-income countries. Adherence and efficacy data are needed to determine cost-effectiveness.
Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-HIV Agents; Disease Transmission, Infectious; Female; HIV Infections; Health Care Costs; Humans; Male; Middle Aged; Pre-Exposure Prophylaxis; Pregnancy; Tenofovir; Young Adult
PubMed: 29424774
DOI: 10.1097/QAD.0000000000001766 -
The Cochrane Database of Systematic... Jun 2019Acute otitis media (AOM), or acute middle ear infection, is one of the most frequently occurring childhood diseases, and the most common reason given for prescribing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute otitis media (AOM), or acute middle ear infection, is one of the most frequently occurring childhood diseases, and the most common reason given for prescribing antibiotics in this age group. Guidelines often recommend antibiotics as first-line treatment for severe AOM. However, antibiotics also lead to antibiotic resistance, so preventing episodes of AOM is an urgent priority.
OBJECTIVES
To assess the effects of probiotics to prevent the occurrence and reduce the severity of acute otitis media in children.
SEARCH METHODS
We searched CENTRAL, PubMed, Embase, and three other databases (October 2018), two trial registers (October 2018), and conducted a backwards and forwards citation analysis (August 2018). We did not apply any language, publication date, or publication status restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of children (aged up to 18 years), comparing probiotics with placebo, usual care, or no probiotic.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the eligibility of trials for inclusion and risk of bias of the included trials, and extracted data using pre-piloted data extraction forms. We analysed dichotomous data as either risk ratio (RR) or odds ratios (OR) and continuous data as mean differences (MD).
MAIN RESULTS
We included 17 RCTs involving 3488 children, of which 16 RCTs were included in the meta-analyses. Of the 16 RCTs that reported the mean age of children, mean age overall was 2.4 years; in 4 RCTs the mean age of children participating in the trial was less than 1 year old; in 2 RCTs the mean age was between 1 and 2 years old; and in 10 RCTs the mean age was older than 2 years. Probiotic strains evaluated by the trials varied, with 11 of the included RCTs evaluating Lactobacillus-containing probiotics, and six RCTs evaluating Streptococcus-containing probiotics.The proportion of children (i.e. the number of children in each group) experiencing one or more episodes of AOM during the treatment was lower for those taking probiotics (RR 0.77, 95% confidence interval (CI) 0.63 to 0.93; 16 trials; 2961 participants; number needed to treat for an additional beneficial outcome (NNTB) = 10; moderate-certainty evidence).Post hoc subgroup analysis found that among children not prone to otitis media, a lower proportion of children receiving probiotics experienced AOM (RR 0.64, 95% CI 0.49 to 0.84; 11 trials; 2227 participants; NNTB = 9; moderate-certainty evidence). However, among children who were otitis prone, there was no difference between probiotic and comparator groups (RR 0.97, 95% CI 0.85 to 1.11; 5 trials; 734 participants; high-certainty evidence). The test for subgroup differences was significant (P = 0.007).None of the included trials reported on the severity of AOM.The proportion of children experiencing adverse events did not differ between the probiotic and comparator groups (OR 1.54, 95% CI 0.60 to 3.94; 4 trials; 395 participants; low-certainty evidence).Probiotics decreased the proportion of children taking antibiotics for any infection (RR 0.66, 95% CI 0.51 to 0.86; 8 trials; 1768 participants; NNTB = 8; moderate-certainty evidence). Test for subgroup differences (use of antibiotic specifically for AOM, use of antibiotic for infections other than AOM) was not significant.There was no difference in the mean number of school days lost (MD -0.95, 95% CI -2.47 to 0.57; 5 trials; 1280 participants; moderate-certainty evidence). There was no difference between groups in the level of compliance in taking the intervention (RR 1.02, 95% CI 0.99 to 1.05; 5 trials; 990 participants).Probiotics decreased the proportion of children having other infections (RR 0.75, 95% CI 0.65 to 0.87; 11 trials; 3610 participants; NNTB = 12; moderate-certainty evidence). Test for subgroup differences (acute respiratory infections, gastrointestinal infections) was not significant.Probiotic strains trialled and their dose, frequency, and duration of administration varied considerably across studies, which likely contributed to the substantial levels of heterogeneity. Sensitivity testing of funnel plots did not reveal publication bias.
AUTHORS' CONCLUSIONS
Probiotics may prevent AOM in children not prone to AOM, but the inconsistency of the subgroup analyses suggests caution in interpreting these results. Probiotics decreased the proportion of children taking antibiotics for any infection. The proportion of children experiencing adverse events did not differ between the probiotic and comparator groups. The optimal strain, duration, frequency, and timing of probiotic administration still needs to be established.
Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Disease Susceptibility; Humans; Infant; Otitis Media; Probiotics; Randomized Controlled Trials as Topic
PubMed: 31210358
DOI: 10.1002/14651858.CD012941.pub2