Raised HIV viral load in blood has been associated with accelerated disease progression and increased transmission of infection. To assess the effect of
Plasmodium falciparum
malaria on ...concentrations of HIV in blood, we did a prospective cohort study in Malawi.
We recruited 367 HIV-1-infected adults. Among 334 people aparasitaemic at baseline, 148 had at least one malaria episode during follow-up and received antimalarial treatment. Of these, 77 had HIV-1-RNA measurements at baseline, during malaria, and post-malaria. We used linear regression with generalised estimating equations to assess effect of four definitions of malaria (any parasitaemia, parasite density ⩾2000/μL, febrile parasitaemia, and febrile parasitaemia with parasite density ⩾2000/μl) on changes in log HIV-1 RNA, overall and by baseline CD4 count.
With malaria defined as any parasitaemia, HIV-1-RNA concentration almost doubled between baseline (median 96 215 copies per mL) and malaria (168 901 copies per mL), a 0·25 (95% CI 0·11–0·39) log increase in mean RNA concentration. HIV-1-RNA concentration fell to median 82 058 copies per mL by about 8–9 weeks post-malaria. Increases in HIV-1-RNA were greatest for people with fever, parasite density 2000/μL or greater, and CD4 count more than 300 cells per μL, in whom concentrations rose from median 38 483 copies per mL at baseline to 196 098 copies per mL during malaria, a mean log increase of 0·82 (95% CI 0·55–1·10, p<0·0001), and fell to median 75 331 copies per mL post-malaria. People who remained aparasitaemic showed no changes in HIV-1-RNA concentration.
HIV-infected individuals with malaria have a significantly increased viral load, which might enhance HIV transmission and accelerate disease progression.
Background: Malawi adopted syndromic management of sexually transmitted infections in 1993. Based on clinical efficacy and cost, gentamicin 240 mg intramuscularly, and doxycycline 100 mg twice daily ...× 7 days was selected as the first line regimen to treat urethritis. We sought to establish current laboratory-based Neisseria gonorrhoeae antibiotic susceptibility patterns for Malawi and describe the pattern of susceptibility since syndromic management began. Methods: Between May 15 and August 10, 2007, 126 men with urethritis attending the STD clinic at Kamuzu Central Hospital in Lilongwe had history, genital exam, and urethral swabs taken. All were treated with gentamicin and doxycycline in accordance with Malawi guidelines. Gonorrhea was diagnosed by Gram stain and culture. Antimicrobial susceptibility patterns in gonococcal isolates were determined by disk diffusion and E-test minimum inhibitory concentration (MIC) determination and agar dilution MIC determination. Results: One hundred six isolates were cultured, and MICs were determined for 100. High levels of resistance to tetracycline and penicillin were observed, but isolates were uniformly susceptible to both gentamicin and ciprofloxacin. Susceptibility patterns identified by the agar dilution MIC and E-test MIC agreed. Conclusions: The most recent study continues the trend of high susceptibility of gonococcal isolates to gentamicin in Malawi after 14 years of use and suggests agar dilution MICs may be substituted with the simpler E-test methods in future susceptibility testing. However because of the lack of susceptibility criteria for aminoglycosides for N. gonorrhoeae and the difficulty obtaining clinical/in vitro correlates in this setting, caution should be exercised in using these data for modifying treatment regimens.
This study was conducted to compare viral dynamics in blood and semen between subjects with antibody negative, acute HIV-1 infection and other subjects with later stages of infection.
A prospective ...cohort study was embedded within a cross-sectional study of HIV screening in a Lilongwe, Malawi STD clinic.
Blood samples from HIV antibody negative or indeterminate volunteers were used to detect HIV RNA in plasma using a pooling strategy. Blood and seminal plasma HIV-1 RNA concentrations were measured over 16 weeks.
Sixteen men with acute HIV infection and 25 men with chronic HIV infection were studied. Blood viral load in subjects with acute HIV infection was highest about 17 days after infection (mean +/- SE, 6.9 +/- 0.5 log10 copies/ml), while semen viral load peaked about 30 days after infection (4.5 +/- 0.4 log10 copies/ml). Semen viral load declined by 1.7 log10 to a nadir by week 10 of HIV infection. Semen and blood viral loads were more stable in chronically infected subjects over 16 weeks. Higher semen levels of HIV RNA were noted in subjects with low CD4 cell counts.
These results provide a biological explanation for reported increases in HIV transmission during the very early (acute) and late stages of infection. Recognizing temporal differences in HIV shedding in the genital tract is important in the development of effective HIV prevention strategies.
Newborn screening in the United States and Europe allows early identification of congenital disorders but does not yet exist in most low-resource settings, especially in sub-Saharan Africa. Newborn ...screening can identify multiple inherited hematological disorders, but feasibility and effectiveness for Africa are not fully determined.
Surplus dried blood spot collected in Central Malawi through the HIV Early Infant Diagnosis surveillance program were repurposed and tested by isoelectric focusing for sickle cell disease and trait. Additional genetic testing identified G6PD deficiency and alpha thalassemia.
Testing of 10,529 cards revealed an overall sickle cell trait prevalence of 7.0% (range 3.9-9.7% by district); 10 of 14 infants identified with sickle cell disease (prevalence 0.1%) were located and received care at a specialized clinic. Subsequent testing of 1,329 randomly selected cards identified alpha thalassemia trait in 45.7% of samples, and G6PD deficiency in 20.4% of males and 3.4% of females, with 29.0% of females as heterozygous carriers.
Inherited hematological disorders are common in Central Malawi; early identification through newborn screening can improve clinical outcomes and should be supported throughout Africa.
The protective effect of insecticide-treated bed nets against individual-level malaria transmission is well known, however community-level effects are less understood. Protective effects from ...community-level bed net use against malaria transmission have been observed in clinical trials, however, the relationship is less clear outside of a controlled research setting. The objective of this research was to investigate the effect of community-level bed net use against malaria transmission outside of a bed net clinical trial setting in Lilongwe, Malawi following national efforts to scale-up ownership of long-lasting, insecticide-treated bed nets.
An annual, cross-sectional, household-randomized, malaria transmission intensity survey was conducted in Lilongwe, Malawi (2011-2013). Health, demographic, and geographic-location data were collected. Participant blood samples were tested for Plasmodium falciparum presence. The percentage of people sleeping under a bed net within 400-m and 1-km radii of all participants was measured. Mixed effects logistic regression models were used to measure the relationship between malaria prevalence and surrounding bed net coverage. Each year, 800 people were enrolled (400 <5 years; 200 5-19 years; 200 ≥20 years; total n = 2400).
From 2011 to 2013, malaria prevalence declined from 12.9 to 5.6%, while bed net use increased from 53.8 to 78.6%. For every 1% increase in community bed net coverage, malaria prevalence decreased among children under 5 years old adjusted odds ratio: 0.98 (0.96, 1.00). Similar effects were observed in participants 5-19 years unadjusted odds ratio: 0.98 (0.97, 1.00); the effect was attenuated after adjusting for individual-level bed net use. Community coverage was not associated with malaria prevalence among adults ≥20 years. Supplemental analyses identified more pronounced indirect protective effects from community-level bed net use against malaria transmission among children under 5 years who were sleeping under a bed net adjusted odds ratio: 0.97 (0.94, 0.99), compared to children who were not sleeping under a bed net adjusted odds ratio: 0.99 (0.97, 1.01).
Malawi's efforts to scale up ownership of long-lasting, insecticide-treated bed nets are effective in increasing reported use. Increased community-level bed net coverage appears to provide additional protection against malaria transmission beyond individual use in a real-world context.
The World Health Organization has selected Malawi as one of three sites to pilot the roll-out of RTS,S/AS01 in phase 4 trials. As policy discussions for the expanded use of RTS,S/AS01 continue, it ...will be critical to determine the performance of the vaccine according to seasonal patterns of malaria transmission in regions of Africa. Given waning vaccine efficacy over time, this secondary analysis demonstrates that administering the vaccine to children in the months prior to malaria season could maximize impact of the vaccine. We followed children (5-17 months) and infants (6-12 weeks) assigned to one of three groups: (1) vaccine with four doses; (2) vaccine with three doses; (3) control. The primary endpoint was defined as episodes of clinical malaria. During the 4-years of follow-up, 658 of 1544 (42.6%) children and infants had at least one episode of clinical malaria. With each 1-inch increase in rainfall per month there was an associated increase in the rate of malaria by 12.6% (95% CI 9.6%, 15.6%, P < 0.0001) among children and 15.9% (95% CI 12.8%, 18.9%, P < 0.0001) among infants. There was no evidence of effect modification of vaccine efficacy by precipitation (89% power).
Opioid agonist treatment (OAT) is an effective method of addiction treatment and HIV prevention. However, globally, people who inject drugs (PWID) have insufficient OAT uptake. To expand OAT access ...and uptake, policymakers, program developers and healthcare providers should be aware of barriers to and facilitators of OAT uptake among PWID.
As a part of the HPTN 074 study, which assessed the feasibility of an intervention to facilitate HIV treatment and OAT in PWID living with HIV in Indonesia, Ukraine, and Vietnam, we conducted in-depth interviews with 37 HIV-positive PWID and 25 healthcare providers to explore barriers to and facilitators of OAT uptake. All interviews were audio-recorded, transcribed, translated into English, and coded in NVivo for analysis. We developed matrices to identify emergent themes and patterns.
Despite some reported country-specific factors, PWID and healthcare providers at all geographic locations reported similar barriers to OAT initiation, such as complicated procedures to initiate OAT, problematic clinic access, lack of information on OAT, misconceptions about methadone, financial burden, and stigma toward PWID. However, while PWID reported fear of drug interaction (OAT and antiretroviral therapy), providers perceived that PWID prioritized drug use over caring for their health and hence were less motivated to take up ART and OAT. Motivation for a life change and social support were reported to be facilitators.
These results highlight a need for support for PWID to initiate and retain in drug treatment. To expand OAT in all three countries, it is necessary to facilitate access and ensure low-threshold, financially affordable OAT programs for PWID, accompanied with supporting interventions. PWID attitudes and beliefs about OAT indicate the need for informational campaigns to counter misinformation and stigma associated with addiction and OAT (especially methadone).
BackgroundTo assess the effects of human immunodeficiency virus (HIV) infection on susceptibility to malaria, we compared the incidence rates of malaria by HIV type 1 (HIV-1) serostatus, baseline ...blood HIV-1 RNA concentration, and baseline CD4 cell count, over the course of a malaria season MethodsWe followed a cohort of 349 adults in Malawi. For the 224 HIV-1–seropositive adults (64% of the cohort), we measured HIV-1 RNA concentration (n=187) and CD4 cell count (n=184) at baseline. Parasitemia was defined as presence of asexual parasites on a thick film of blood and was treated with sulfadoxine/pyrimethamine (SP), in accordance with national policy. Hazard ratios (HRs) of parasitemia were estimated using Cox regression. Demographics were adjusted for ResultsHIV-1 seropositivity was associated with parasitemia (adjusted HR, 1.8 95% confidence interval {CI}, 1.2–2.7 for a first parasitemia episode; adjusted HR, 2.5 95% CI, 1.5–4.2 for a second parasitemia episode >14 days after the first episode; adjusted HR, 1.9 95% CI, 1.4–2.6 for parasitemia overall). Treatment failure (parasitemia ⩽14 days after SP treatment) did not differ by HIV-1 serostatus (risk ratio, 1.3 95% CI, 0.5–3.2). HIV-1 RNA concentrations and CD4 cell counts were moderately but inconsistently associated with parasitemia. A high parasite density with fever was associated with HIV-1 seropositivity and low CD4 cell count ConclusionHIV-infected adults in malaria-endemic areas are at increased risk for malaria. Where possible, additional malaria prevention efforts should be targeted at this population
We evaluated the efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine prophylaxis for 28 weeks during breast-feeding to reduce postnatal transmission of human ...immunodeficiency virus type 1 (HIV-1) in Malawi.
We randomly assigned 2369 HIV-1-positive, breast-feeding mothers with a CD4+ lymphocyte count of at least 250 cells per cubic millimeter and their infants to receive a maternal antiretroviral regimen, infant nevirapine, or no extended postnatal antiretroviral regimen (control group). All mothers and infants received perinatal prophylaxis with single-dose nevirapine and 1 week of zidovudine plus lamivudine. We used the Kaplan-Meier method to estimate the cumulative risk of HIV-1 transmission or death by 28 weeks among infants who were HIV-1-negative 2 weeks after birth. Rates were compared with the use of the log-rank test.
Among mother-infant pairs, 5.0% of infants were HIV-1-positive at 2 weeks of life. The estimated risk of HIV-1 transmission between 2 and 28 weeks was higher in the control group (5.7%) than in either the maternal-regimen group (2.9%, P=0.009) or the infant-regimen group (1.7%, P<0.001). The estimated risk of infant HIV-1 infection or death between 2 and 28 weeks was 7.0% in the control group, 4.1% in the maternal-regimen group (P=0.02), and 2.6% in the infant-regimen group (P<0.001). The proportion of women with neutropenia was higher among those receiving the antiretroviral regimen (6.2%) than among those in either the nevirapine group (2.6%) or the control group (2.3%). Among infants receiving nevirapine, 1.9% had a hypersensitivity reaction.
The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding. (ClinicalTrials.gov number, NCT00164736.)
Transmission of HIV-1 is predominantly by heterosexual contact in sub-Saharan Africa, where sexually transmitted diseases (STDs) are also common. Epidemiological studies suggest that STDs facilitate ...transmission of HIV-1, but the biological mechanism remains unclear. We investigated the hypothesis that STDs increase the likelihood of transmission of HIV-1 through increased concentration of the virus in semen.
HIV-1 RNA concentrations were measured in seminal and blood plasma from 135 HIV-1-seropositive men in Malawi; 86 had urethritis and 49 controls did not have urethritis. Men with urethritis received antibiotic treatment according to the guidelines of the Malawian STD Advisory Committee. Samples were analysed at baseline and at week 1 and week 2 after antibiotic therapy in urethritis patients, and at baseline and week 2 in the control group.
HIV-1-seropositive men with urethritis had HIV-1 RNA concentrations in seminal plasma eight times higher than those in seropositive men without urethritis (12·4
vs 1·51×10
4 copies/mL, p=0·035), despite similar CD4 counts and concentrations of blood plasma viral RNA. Gonorrhoea was associated with the greatest concentration of HIV-1 in semen (15·8×10
4 copies/mL). After the urethritis patients received antimicrobial therapy directed against STDs, the concentration of HIV-1 RNA in semen decreased significantly (from 12·4×10
4 copies/mL to 8·91×10
4 copies/mL at 1 week p=0·03 and 4·12×10
4 copies/mL at 2 weeks p=0·0001). Blood plasma viral RNA concentrations did not change. There was no significant change in seminal plasma HIV-1 RNA concentrations during the 2-week period in the control group (p=0·421).
These results suggest that urethritis increases the infectiousness of men with HIV-1 infection. HIV-1-control programmes, which include detection and treatment of STDs in patients already infected with HIV-1, may help to curb the epidemic. Targeting of gonococcal urethritis may be a particularly effective strategy.
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