Predictors of unstructured antiretroviral treatment interruption and resumption among HIV-positive individuals in Canada.

OBJECTIVES: Sustained optimal use of combination antiretroviral therapy (cART) has been shown to decrease morbidity, mortality and HIV transmission. However, incomplete adherence and treatment interruption (TI) remain challenges to the full realization of the promise of cART. We estimated trends and predictors of treatment interruption and resumption among individuals in the Canadian Observational Cohort (CANOC) collaboration. METHODS: cART-naïve individuals ≥ 18 years of age who initiated cART between 2000 and 2011 were included in the study. We defined TIs as ≥ 90 consecutive days off cART. We used descriptive analyses to study TI trends over time and Cox regression to identify factors predicting time to first TI and time to treatment resumption after a first TI. RESULTS: A total of 7633 participants were eligible for inclusion in the study, of whom 1860 (24.5%) experienced a TI. The prevalence of TI in the first calendar year of cART decreased by half over the study period. Our analyses highlighted a higher risk of TI among women [adjusted hazard ratio (aHR) 1.59; 95% confidence interval (CI) 1.33-1.92], younger individuals (aHR 1.27; 95% CI 1.15-1.37 per decade increase), earlier treatment initiators (CD4 count ≥ 350 vs. <200 cells/µL: aHR 1.46; 95% CI 1.17-1.81), Aboriginal participants (aHR 1.67; 95% CI 1.27-2.20), injecting drug users (aHR 1.43; 95% CI 1.09-1.89) and users of zidovudine vs. tenofovir in the initial cART regimen (aHR 2.47; 95% CI 1.92-3.20). Conversely, factors predicting treatment resumption were male sex, older age, and a CD4 cell count <200 cells/µL at cART initiation. CONCLUSIONS: Despite significant improvements in cART since its advent, our results demonstrate that TIs remain relatively prevalent. Strategies to support continuous HIV treatment are needed to maximize the benefits of cART.

Hypertension in pregnancy among HIV-infected women in sub-Saharan Africa: prevalence and infant outcomes.

This analysis was performed to determine the prevalence of hypertension and association of MAP (mean arterial pressure) with birth outcomes among HIV-infected pregnant women not taking antiretrovirals. HIV-infected pregnant women, enrolled into the HPTN024 trial in Tanzania, Malawi and Zambia were followed up at 26-30, 36 weeks, and delivery. The prevalence of hypertension was <1% at both 20-24 weeks and 26-30 weeks and 1.7% by 36 weeks. A 5 mm Hg elevation in MAP increased the risk of stillbirth at 20-24 weeks by 29% (p = 0.001), 32% (p = 0.001) at 26-30 weeks and of low birth weight (LBW) at 36 weeks by 26% (p = 0.001). MAP was not associated with stillbirth at 36 weeks, LBW prior to 36 weeks, preterm birth, neonatal mortality or the risk of maternal to child transmission (MTCT) of HIV.

The role of men in women's acceptance of an intravaginal gel in a randomized clinical trial in Blantyre, Malawi: a qualitative and quantitative analysis.

Survey questionnaires and focus group discussions were used to investigate the association between a female participant's acceptance and her perception of her male partner's acceptance of an intravaginal gel as a prototype microbicide. Women who perceived their male partners would accept using the gel were more likely to highly accept the gel as compared to women who perceived their male partners would not accept using the gel (OR=24.57; 95%CI: 16.49-36.61). Qualitative analysis supported a positive association between female acceptability and perceived male partner acceptability. Qualitative research reiterated this finding and also found that men and women had different approaches to assess gel acceptability. Women integrated perceptions of their partner's acceptance into their own acceptability and reported their partners had positive experiences. In contrast, men reported a more neutral experience with the gel and assessed the gel without overt consideration of their partner's experiences. These results indicate that female perceptions of male partner acceptability and actual male partner acceptability need to be considered when addressing female-controlled product acceptability and use.

Genital tract infections among HIV-infected pregnant women in Malawi, Tanzania and Zambia.

SUMMARY: The aim of this study was to compare the prevalence and factors associated with genital tract infections among HIV-infected pregnant women from African sites. Participants were recruited from Blantyre and Lilongwe, Malawi; Dar es Salaam, Tanzania; and Lusaka, Zambia. Genital tract infections were assessed at baseline. Of 2627 eligible women enrolled, 2292 were HIV-infected. Of these, 47.8% had bacterial vaginosis (BV), 22.4% had vaginal candidiasis, 18.8% had trichomoniasis, 8.5% had genital warts, 2.6% had chlamydia infection, 2.2% had genital ulcers and 1.7% had gonorrhoea. The main factors associated with genital tract infections included genital warts (adjusted odds ratio [AOR] 1.8, 95% CI 1.2-2.7), genital ulcers (AOR 2.4, 95% CI 1.2-5.1) and abnormal vaginal discharge (AOR 2.5, 95% CI 1.9-3.3) for trichomoniasis. BV was the most common genital tract infection followed by candidiasis and trichomoniasis. Differences in burdens and risk factors call for enhanced interventions for identification of genital tract infections among HIV-infected women.

Micronutrient supplements and mortality of HIV-infected adults with pulmonary TB: a controlled clinical trial.

SETTING: Zomba and Blantyre, Malawi, Africa. OBJECTIVES: To determine whether daily micronutrient supplementation reduces the mortality of human immunodeficiency virus (HIV) infected adults with pulmonary tuberculosis (TB). DESIGN: A randomised, controlled clinical trial of micronutrient supplementation for HIV-positive and HIV-negative adults with pulmonary TB. Participants were enrolled at the commencement of chemotherapy for sputum smear-positive pulmonary TB and followed up for 24 months. RESULTS: A total of 829 HIV-positive and 573 HIV-negative adults were enrolled. During follow-up, 328 HIV-positive and 17 HIV-negative participants died. The proportion of HIV-positive participants who died in the micronutrient and placebo groups was 38.7% and 40.4%, respectively (P = 0.49). Micronutrient supplementation did not reduce mortality (hazard ratio [HR] 0.93, 95%CI 0.75-1.15) among HIV-positive adults. CONCLUSIONS: Micronutrient supplementation at the doses used in this study does not reduce mortality in HIV-positive adults with pulmonary TB in Malawi.

Epidemiology and microbiology of subclinical mastitis among HIV-infected women in Malawi.

The epidemiology and microbiology of subclinical mastitis, a risk factor for perinatal HIV transmission, have not been well characterized. In all, 250 HIV-infected women were followed from two weeks to 12 months postpartum in Blantyre, Malawi, and subclinical mastitis was assessed by breast milk leukocyte counts. The point prevalence of subclinical mastitis at 2, 4, 6, 10, and 14 weeks, and 6, 9, and 12 months was 12.2%, 7.8%, 6.8%, 3.7%, 10.6%, 5.1%, 4.9%, and 1.9%, respectively (P = 0.002), and 27.2% of women had at least one episode of subclinical mastitis. There was no significant relationship between maternal plasma HIV load or parity and subclinical mastitis. Staphylococcus aureus was isolated in 30% of women with subclinical mastitis, and the proportion of women with positive cultures decreased during follow-up (P = 0.02). Subclinical mastitis is prevalent among breastfeeding mothers and further studies are needed to characterize the differences between infectious and non-infectious subclinical mastitis.

Viral levels in newborn African infants undergoing primary HIV-1 infection.

We examined weekly changes in viral levels in seven untreated infants infected with HIV at birth. Viral levels spiked immediately but reverted quickly to plateau levels typical of infant HIV infection within 2 weeks of first detected viraemia. We speculated that the depletion of naive, susceptible cells is responsible for the rapid decrease in spike levels and that the rapid replacement of lymphocytes in infants causes the high plateau viral levels (10(5) copies/ml) to be sustained.

Reported condom use is not associated with incidence of sexually transmitted diseases in Malawi.

OBJECTIVES: To establish frequency of reported condom use and validate reliability of self-reporting among urban women in Malawi. DESIGN: Cross-sectional survey in antenatal women in 1989 and 1993. Prospective study in cohort first surveyed in 1989. METHODS: A total of 6561 women in 1989 and 2460 women in 1993 answered questions about condom use and sexual activity, had a physical examination and were screened for HIV. A subset of women from the 1989 screening were administered a questionnaire and tested for syphilis, Neisseria gonorrhoeae and Trichomonas vaginalis infections every 6 months. RESULTS: Although between the two cross-sectional studies intermittent condom use increased from 6 to 15% (P < 0.001) with no difference according to HIV infection, consistent use was reported by less than 1%. In the prospective study, women reported a higher condom use at any visit than either group assessed cross-sectionally. Consistent condom use peaked at 62% in the first 6 months, but declined to as low as 8% in the second year of follow-up. Condom use at each visit, either intermittent or consistent, was higher in HIV-seropositive than HIV-seronegative women. Overall, the incidence of gonorrhea, trichomoniasis and syphilis did not decline in women reporting consistent condom use. CONCLUSIONS: In prospectively followed women reports of consistent condom use was substantially higher than in cross-sectional surveys, but rapidly decreased over time, irrespective of HIV status. The presence of new sexually transmitted diseases suggests that this population of urban women overreports condom use or underreports sexual activity, or both. Intensive and sustained education is needed to achieve consistent condom use. Biologic markers of sexual activity are useful in interpreting reported condom use.

PIP: To determine the frequency of reported condom use and validate the reliability of self-reporting among urban women in Malawi, 6561 women in 1989 and 2460 women in 1993 answered survey questions about condom use and sexual activity, had a physical examination, and were screened for HIV. A subset of women from the 1989 screening were administered a questionnaire and tested for syphilis, gonorrhea, and Trichomonas vaginalis infections every six months. The study populations consisted of consecutive women presenting for their first antenatal visit to Queen Elizabeth Hospital in Blantyre, Malawi. Intermittent condom use increased from 6% to 15% between the two cross-sectional studies, with no difference according to HIV infection; consistent condom use was reported by less than 1%. In the prospective study, women reported higher condom use at any visit than either group assessed cross-sectionally. Consistent condom use peaked at 62% in the first six months, but declined to as low as 8% during the second year of follow-up. Condom use at each visit, either intermittent or consistent, was higher among HIV-seropositive than HIV-seronegative women. Overall, the incidence of syphilis, gonorrhea, and trichomoniasis did not decline in women reporting consistent condom use. This incidence of new sexually transmitted diseases suggests that the studied population either overreports condom use or underreports sexual activity, or both.

Does umbilical cord blood polymerase chain reaction positivity indicate in utero (pre-labor) HIV infection?

OBJECTIVE: To compare risk factors for infants whose cord blood was positive for HIV DNA with those who were cord blood-negative but found to be HIV DNA-positive in early infancy. METHODS: In 1994, infants born to HIV-infected women were enrolled in a study in Blantyre, Malawi. Birth weight and transmission risk factors from cord blood-positive infants were compared with cord blood-negative/HIV-positive infants on their first postnatal visit (4-7 weeks of age). Testing for HIV DNA on cord and peripheral blood was performed by polymerase chain reaction. RESULTS: Of 249 HIV-infected infants (overall transmission rate, 26%), 83 (33%) were cord blood-positive and 166 were initially cord blood-negative. The mean birth weight was 2.1% (59 g) lighter in cord blood-positive infants than initially cord blood-negative infants; initially cord blood-negative infants were 2.8% (80 g) lighter than uninfected infants born to HIV-infected women. There were no significant differences in the risk factors for infection between HIV-infected cord blood-positive and -negative infants; when transmission was increased, both HIV-infected cord blood-positive and -negative infants contributed to the increase in a similar proportion. INTERPRETATION: It was concluded that umbilical cord blood positivity for HIV DNA did not identity a subset of in utero HIV-infected infants and suggested that HIV-infected cord blood-positive and -negative infants have similar timing and routes of HIV infection.

Trends of HIV-1 and sexually transmitted diseases among pregnant and postpartum women in urban Malawi.

OBJECTIVES: To examine rates of HIV-1 and sexually transmitted disease (STD) among pregnant and postpartum women in urban Malawi, Africa. DESIGN: Serial cross-sectional surveys and a prospective study. METHODS: Three major surveys were conducted in 1990, 1993 and 1994/1995. Consecutive first-visit antenatal women and women giving birth at the Queen Elizabeth Central Hospital were tested for HIV and STD after counseling and obtaining informed consent. Unlinked, anonymous HIV testing was also conducted on smaller samples of antenatal women in the same hospital to provide annual prevalence data. HIV-seronegative postpartum women from the 1990 and 1993 surveys were enrolled in a prospective study to determine HIV incidence. RESULTS: HIV seroprevalence rose from 2.0% in 1985 to 32.8% in 1996, a 16-fold increase. The highest age-specific HIV prevalence was in the following age-groups: 20-24 years during 1990, 25-29 years during 1993, and 30-34 years during 1996. Among 1173 women followed for a median of 30.9 months, HIV incidence was 5.98 per 100 person-years in women aged < 20 years and declined steadily in older women. The prevalence of STD significantly declined among both HIV-positive and negative women. This decline in STD prevalence, however, was not accompanied by increased condom use over time. CONCLUSIONS: Among urban childbearing women in Malawi, incidence of HIV is highest among young women while, currently, prevalence is highest among older women. Recent declines in STD prevalence suggest that HIV prevention programs are having an impact either through improved STD diagnosis and treatment or reduced risk behaviors. Sequential cross-sectional STD prevalence measures may be useful in monitoring effectiveness of STD and HIV prevention activities.

PIP: Prevalence rates of HIV-1 and other sexually transmitted diseases (STDs) among pregnant and postpartum women were investigated in sequential, cross-sectional studies (1990, 1993, and 1994-95) conducted at Queen Elizabeth Central Hospital in Blantyre, Malawi. Annual anonymous, unlinked testing revealed a linear increase in HIV-1 prevalence among antenatal patients from 2.0% in 1985 to 32.8% in 1996. Analysis of demographic attributes of women enrolled in the 1990 and 1993 surveys of consecutive, first-visit antenatal women (n = 6603 and 2161, respectively) and the 1994-95 study of all women giving birth at the hospital during a 6-month period (n = 6964) indicated that HIV-infected women were most likely to be young, with fewer pregnancies, and be more educated. The highest age-specific HIV prevalence shifted from 20-24 years in 1990 to 30-34 years in 1996, indicating an aging cohort of women who became infected at a younger age. Reported lifetime use of condoms increased from 5.6% in 1990 to 17.5% in 1993, then declined to 4.9% in 1995; condom use was consistently higher among HIV-positive than HIV-negative women. The prevalence of all STDs (syphilis, trichomoniasis, gonorrhea, and genital warts and ulcers) declined significantly during 1990-96, with the most consistent decreases recorded among HIV-positive women. In a follow-up study of 1173 HIV-seronegative, postpartum women evaluated for 2302 person-years (average duration, 30.9 months), 97 seroconverted (4.21/100 person-years). The seroconversion rate declined steadily from 21.26/100 person-years in 1990 to 1.11/100 person-years in 1994-95. These findings are consistent with those from other sub-Saharan African countries, indicating a rapid increase in HIV prevalence followed by stabilization within about 10 years of the onset of the epidemic. The large decline in STD prevalence in the antenatal population suggests that Malawi's national AIDS prevention program is having an impact, either through improved STD diagnosis and treatment or reduced risk behaviors.

Association of HIV-1 load and CD4 lymphocyte count with mortality among untreated African children over one year of age.

OBJECTIVE: To examine the association of viral load and CD4 lymphocyte count with mortality among HIV-infected children over one year of age. DESIGN: A prospective study. HIV-infected children were enrolled during the first year of life and followed for more than 2 years at the Queen Elizabeth Central Hospital in Blantyre, Malawi (southeast Africa). METHODS: Morbidity and mortality information was collected every 3 months, and physical examination and blood testing (for viral level and CD4 cell percentage) were performed every 6 months. Kaplan-Meier analyses and proportional hazards models were used to estimate survival and to examine the association of primary predictors with mortality. RESULTS: Of 155 HIV-infected children originally enrolled, 115 (74%) had viral load testing and 82 (53%) had both viral load and CD4 cell percentage testing after their first year. Among children over one year of age, significant associations were found between mortality and the log10 viral load and CD4 cell percentage in both univariate and multivariate models. Independent of the CD4 cell value, a one unit log10 increase in HIV RNA level increased the hazard of child mortality by more than twofold. Children with low CD4 cell counts (< 15%) and high viral loads (> or = 250,000 copies/ml median value) had the worst survival; children with high CD4 cell counts (> or = 15%) and low viral loads (< 250,000 copies/ml) had the best survival. CONCLUSION: As in developed countries, viral load and CD4 cell count are the main predictors of mortality among African children. Making these tests available adds to the challenges to be considered if antiviral therapies were to be adopted in these countries.

Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV.

BACKGROUND: Cross-sectional studies suggest an association between bacterial vaginosis (BV) and HIV-1 infection. However, an assessment of a temporal effect was not possible. OBJECTIVES: To determine the association of BV and other disturbances of vaginal flora with HIV seroconversion among pregnant and postnatal women in Malawi, Africa. DESIGN: Longitudinal follow-up of pregnant and postpartum women. METHODS: Women attending their first antenatal care visit were screened for HIV after counselling and obtaining informed consent. HIV-seronegative women were enrolled and followed during pregnancy and after delivery. These women were again tested for HIV at delivery and at 6-monthly visits postnatally. Clinical examinations and collection of laboratory specimens (for BV and sexually transmitted diseases) were conducted at screening and at the postnatal 6-monthly visits. The diagnosis of BV was based on clinical criteria. Associations of BV and other risk factors with HIV seroconversion, were examined using contingency tables and multiple logistic regression analyses on antenatal data, and Kaplan-Meier proportional hazards analyses on postnatal data. RESULTS: Among 1196 HIV-seronegative women who were followed antenatally for a median of 3.4 months, 27 women seroconverted by time of delivery. Postnatally, 97 seroconversions occurred among 1169 seronegative women who were followed for a median of 2.5 years. Bacterial vaginosis was significantly associated with antenatal HIV seroconversion (adjusted odds ratio = 3.7) and postnatal HIV seroconversion (adjusted rate ratio = 2.3). There was a significant trend of increased risk of HIV seroconversion with increasing severity of vaginal disturbance among both antenatal and postnatal women. The approximate attributable risk of BV alone was 23% for antenatal HIV seroconversions and 14% for postnatal seroconversions. CONCLUSIONS: This prospective study suggests that progressively greater disturbances of vaginal flora, increase HIV acquisition during pregnancy and postnatally. The screening and treating of women with BV could restore normal flora and reduce their susceptibility to HIV.

The effect of Plasmodium falciparum malaria on HIV-1 RNA blood plasma concentration.

OBJECTIVES: This study was undertaken to determine the relative effect of malaria infection on HIV concentration in blood plasma, and prospectively to monitor viral concentrations after antimalarial therapy. DESIGN: A prospective, double cohort study was designed to compare the blood HIV-1 RNA concentrations of HIV-positive individuals with and without acute malaria illness. Subjects were followed for 4 weeks after successful malaria therapy, or for 4 weeks from enrollment (controls). METHODS: Malawian adults with symptomatic Plasmodium falciparum parasitemia (malaria group) and asymptomatic, aparasitemic blood donors (control group) were tested for HIV-1 antibodies to identify appropriate study groups. The malaria group received antimalarial chemotherapy only and were followed with sequential blood films. In both groups, blood plasma HIV-1 RNA viral concentrations were determined at enrollment and again at 1, 2 and 4 weeks. RESULTS: Forty-seven malaria patients and 42 blood donors were enrolled. At enrollment blood plasma HIV-1 RNA concentrations were approximately sevenfold higher in patients with malaria than in blood donors (medians 15.1 x 10(4) and 2.24 x 10(4) copies/ml, respectively, P = 0.0001). No significant changes in median HIV-1 concentrations occurred in the 21 blood donors followed to week 4 (P = 0.68). In the 27 subjects successfully treated for malaria who were followed to week 4, a reduction in plasma HIV-1 RNA was observed from a median of 19.1 x 10(4) RNA copies/ml at enrollment, to 12.0 x 10(4) copies/ml at week 4, (P = 0.02). Plasma HIV-1 concentrations remained higher in malaria patients than controls (median 12.0 x 10(4) compared with 4.17 x 10(4) copies/ml, P = 0.086). CONCLUSIONS: HIV-1 blood viral burden is higher in patients with P. falciparum malaria than in controls and this viral burden can, in some patients, be partly reduced with antimalarial therapy.

Mortality after the first year of life among human immunodeficiency virus type 1-infected and uninfected children.

BACKGROUND: HIV-infected and uninfected children who survived their first year of life were prospectively followed in Malawi to assess levels of mortality and related risk factors during the second and third years of life. METHODS: Children with known HIV status from an earlier perinatal intervention trial were enrolled. These children [HIV-infected (Group A); HIV-uninfected but born to HIV-seropositive mothers (Group B); and children born to HIV-seronegative mothers (Group C)] were followed every 3 months until age 36 months. Mortality data were collected at each visit. Immunologic data (CD4+ percent) were collected at or immediately after enrollment. RESULTS: Overall 702 children were enrolled and 83 children died during follow-up. The mortality rate per 1000 person years of observation was 339.3 among Group A children, 46.3 among Group B children and 35.7 among Group C children. Among HIV-infected children the cumulative proportion surviving to age 24 months was 70% and those surviving to age 36 months was 55%. By age 32 months none of the severely immunosuppressed (CD4% < 15%) children had survived. The mortality differentials between HIV-infected and uninfected children persisted after adjusting for several risk factors. The major causes of death among infected children (n = 52) were wasting and respiratory conditions. CONCLUSIONS: Although all HIV-infected children had received childhood immunizations, mortality was high. Management of these children should include aggressive antimicrobial treatment, and evaluation of prophylactic regimens should be considered.

The effect of human immunodeficiency virus infection on birthweight, and infant and child mortality in urban Malawi.

BACKGROUND: Low birthweight, prematurity and intra-uterine growth retardation (IUGR) are major determinants of child survival. Therefore, it is important to assess excess mortality due to human immunodeficiency virus (HIV) infection in populations where low birthweight is common. METHODS: A prospective study was conducted on 1385 children born to seropositive and seronegative women in urban Malawi. Children were regularly examined and tested for HIV. RESULTS: The mortality rate of children of HIV seropositive mothers was substantially higher (223/1000 at 12 months, 317/1000 at 24 months and 360/1000 at 30 months) than that of children of seronegative mothers (68/1000 at 12 months, 106/1000 at 24 months and 118/1000 at 30 months). The incidence of prematurity and IUGR was also higher in infants of HIV seropositive mothers than in infants of seronegative mothers (12.7% versus 3.8%, P < 0.001 for premature and 7.7% versus 4.4%, P = 0.02 for IUGR infants). The mother-to-infant HIV-1 transmission rate was 35.1%. After 12 months of age, HIV infected children showed the highest mortality; however, uninfected children of HIV seropositive and children of HIV seronegative mothers had similar mortality. The mean birthweight of HIV infected and uninfected children was not significantly different. In HIV infected children the most frequent causes of death were diarrhoea, pneumonia and failure to thrive. Less common risk factors for child mortality included active maternal syphilis and cervicitis/vaginitis. CONCLUSION: The substantial difference in survival among children of HIV infected and uninfected mothers suggests that mortality could be reduced if HIV infection were not a risk factor. To decrease childhood mortality, a combination of interventions such as treatment of sexually transmitted infections during pregnancy and measures to reduce mother-to-infant transmission should be adopted.

PIP: Low birth weight, prematurity, and intra-uterine growth retardation (IUGR) are major determinants of child survival. Therefore, it is important to assess excess mortality due to human immunodeficiency virus (HIV) infection in populations where low birth weight is common. A prospective study was conducted on a total of 1385 children born to 679 HIV-seropositive and 687 seronegative women in urban Malawi. Children were regularly examined and tested for HIV. The mortality rate of children of HIV-seropositive mothers was substantiality higher (223/1000 at 12 months, 317/1000 at 24 months, and 360/1000 at 30 months, p 0.0001) than that of children of seronegative mothers (68/1000 at 12 months, 106/1000 at 24 months, and 118/1000 at 30 months). The incidence of prematurity and IUGR was also higher in infants of HIV-seropositive mothers than in infants of seronegative mothers (12.5% versus 3.8%, p 0.001 for premature and 7.7% versus 4.4%, p = 0.02 for IUGR infants). The mother-to-infant HIV-1 transmission rate was 35.1%. The overall incidence of low birth weight was 14.1%, but the incidence was 20.1% among children of seropositive mothers and 8.3% among those of seronegative mothers (p 0.001). After 12 months of age, HIV-infected children showed the highest mortality; however, uninfected children of HIV-seropositive and children of HIV-seronegative mothers had similar mortality. The mean birth weight of HIV-infected and uninfected children was not significantly different. In HIV-infected children the most frequent causes of death were diarrhea, pneumonia, and failure to thrive. Less common risk factors for child mortality included active maternal syphilis and cervicitis/vaginitis. A possible enrolment bias could have resulted in lower mortality estimates among babies of HIV-seronegative mothers. To decrease childhood mortality, a combination of interventions such as treatment of sexually transmitted infections during pregnancy and measures to reduce mother-to-infant transmission should be adopted.

Predictors and impact of losses to follow-up in an HIV-1 perinatal transmission cohort in Malawi.

BACKGROUND: Large simple trials which aim to study therapeutic interventions and epidemiological associations of human immunodeficiency virus (HIV) infection, including perinatal transmission, in Africa may have substantial rates of loss to follow-up. A better understanding of the characteristics and the impact of women and children lost to follow-up is needed. METHODS: We studied predictors and the impact of losses to follow-up of infants born in a large cohort of delivering women in urban Malawi. The cohort was established as part of a trial of vaginal cleansing with chlorhexidine during delivery to prevent mother-to-infant transmission of HIV. RESULTS: The HIV infection status could not be determined for 797 (36.9%) of 2156 infants born to HIV-infected mothers; 144 (6.7%) with missing status because of various sample problems and 653 (30.3%) because they never returned to the clinic. Notably, the observed rates of perinatal transmission were significantly lower in infants who returned later for determination of their infection status (odds ratio = 0.94 per month, P = 0.03), even though these infants must have had an additional risk of infection from breastfeeding. In multivariate models, infants of lower birthweight (P = 0.003) and, marginally, singletons (P = 0.09) were less likely to return for follow-up. The parents of infants lost to follow-up tended to be less educated (P < 0.001) and more likely to be in farming occupations, although one educated group, teachers and students, were also significantly less likely to return. Of these variables, infant birthweight, twins versus singletons, and maternal education were also associated with significant variation in the observed risk of perinatal transmission among infants of known HIV status. CONCLUSIONS: Several predictors of loss to follow-up were identified in this large HIV perinatal cohort. Losses to follow-up can impact the observed transmission rate and the risk associations in different studies.

PIP: Predictors and the impact of losses to follow-up of infants born to a large HIV- infected cohort of delivering women in urban Malawi were studied. The women enrolled in an intervention trial including vaginal cleansing with chlorhexidine at the time of delivery. Findings showed that of the 2156 infants born to HIV- infected mothers, about 1359 (63.1%) had been diagnosed with HIV infection, 797 (36.9%) with undetermined status, 144 (6.7%) with missing status, and about 653 (30.3%) were never brought back for follow-up. The odds of HIV positivity decreased in the determination of infectious status (P = 0.03) despite the probability of additional transmission from breast-feeding. Late-coming and lost children of less educated parents had similar birth weight (P = 0.50) and were likely less to return. This was probably due to the fact that the fathers of the lost children were farmers. Besides, infant birth weight, twins vs. singletons, and maternal education were affiliated with significant variation in the observed risk of perinatal transmission among HIV-positive infants. Thus, with regard to the intervention trial, the LFU were approximately equal in both groups. There was no evidence that the losses were unbalanced between arms in relation to the predictors of transmission.

Genital tract infections and perinatal transmission of HIV.

In areas of the world where genital tract infections (GTIs) are common, the prevalence of HIV and the rate of mother-to-child transmission (MTCT) of HIV are also high. Although observational studies suggested that GTIs are associated with MTCT of HIV, no controlled clinical trial has confirmed this finding. It is likely that GTIs that cause either discharges or ulcers during pregnancy increase perinatal transmission of HIV. Several potential biological mechanisms might facilitate perinatal transmission. For example, chorioamnionitis, increased viral shedding in cervicovaginal secretions, increased HIV acquisition during pregnancy, inflammatory cytokine production, preterm labor, prolonged rupture of membranes, ascending infection, and increased intrapartum infectious secretions are factors that can be associated with GTIs. Several studies have shown that treating clinical conditions associated with inflammation might alter HIV shedding. It is conceivable that preventing ascending infection or reducing exposure of the infant to infectious material during birth could reduce MTCT. This can possibly be achieved by antimicrobial therapy during pregnancy and intrapartum. Such an approach is practical, is less expensive, and has secondary benefits related to prevention of adverse pregnancy outcomes associated with GTIs. Antibiotics might also complement reductions in MTCT of HIV obtained by antiretrovirals given to the mother around the time of delivery. In addition, antibiotics could reduce infectious causes of morbidity and mortality in infant and mother.

Malnutrition and the severity of lung disease in adults with pulmonary tuberculosis in Malawi.

SETTING: Zomba Central Hospital, Zomba, Malawi. OBJECTIVE: To examine the relationship between malnutrition and the severity of lung disease in human immunodeficiency virus (HIV) positive and negative adults with pulmonary tuberculosis (PTB). DESIGN: Cross-sectional study. METHODS: Chest radiographs and anthropometric measurements were obtained and bioelectrical impedance analysis was conducted in sputum-positive patients with pulmonary tuberculosis. Lung disease in chest radiographs was graded as normal, minimal, moderately advanced and far advanced according to a conventional classification system. RESULTS: Among 319 adults with PTB with or without HIV co-infection, body mass index (BMI), fat mass and phase angle were independently associated with increasing severity of lung disease. Multiple logistic regression analyses showed that BMI, fat mass and phase angle were associated with increasing severity of lung disease among 236 HIV-positive adults, when adjusted for sex, age, and plasma HIV load. CONCLUSION: The severity of lung disease in adults with PTB is associated with the extent of malnutrition, as reflected by BMI and body composition studies using bioelectrical impedance analysis.

Childhood malaria parasitaemia and human immunodeficiency virus infection in Malawi.

PIP: Malaria and human immunodeficiency virus (HIV) infection are major health problems in many areas in Sub-Saharan Africa. An interaction between malaria and HIV infection has been postulated, since both produce similar cellular immune responses, with a lowering of the CD4/CD8 lymphocyte ratio. The frequency of malaria parasitemia was examined in children born to HIV-seropositive and seronegative mothers attending regular postnatal visits. A prospective study on mother-to-infant transmission of HIV had been underway since 1989 in Queen Elizabeth Central Hospital, Blantyre, a major hospital in urban Malawi. Standard HIV serology was performed on pregnant women, after obtaining consent. To reduce the effect of selection bias and seasonality, HIV seropositive (case) and seronegative (control) mothers and their infants were enrolled at delivery. Children included in the study were 503 born to 494 HIV-seropositive mothers and 540 born to 536 HIV-seronegative mothers. At each 3-monthly postpartum visit a Giemsa-stained thick blood film from the child was examined for malaria parasites. Children born to HIV-seropositive mothers were tested for HIV antibodies at 12 and 18 months of age. Of the 353 children born to HIV-seropositive mothers, 82 children (23.2%) were found to be HIV seropositive by enzyme-linked immunosorbent assay and Western blotting at 12 and 18 months. No statistically significant difference was found in frequency of malaria parasitemia by maternal or infant HIV serostatus after controlling for child's age. There was, however, a significant trend of increase in high parasitemia with age, irrespective of the HIV serostatus of the mother or the child. The frequency of parasitemia was higher in the wet season than in the dry season. This study suggests that maternal or infant HIV infection does not alter susceptibility to, or the clinical course of, malaria in infants.^ieng

Assessment of iron status using plasma transferrin receptor in pregnant women with and without human immunodeficiency virus infection in Malawi.

BACKGROUND: Although anemia is highly prevalent during pregnancy and is common during human immunodeficiency virus (HIV) infection, anemia and iron status have not been well characterized in HIV-infected pregnant women. OBJECTIVE: To gain insight into iron status in HIV-infected pregnant women using plasma transferrin receptor and related indicators of anemia. STUDY DESIGN: Plasma transferrin receptor, ferritin, alpha1-acid glycoprotein, C-reactive protein and hemoglobin concentrations were measured in pregnant women, gestational age 18-28 weeks, seen in an urban antenatal clinic in Blantyre, Malawi. RESULTS: The prevalence of anemia among 662 HIV-positive and 190 HIV-negative pregnant women was 73.1% and 50.0%, respectively (P<0.0001). Among HIV-positive and HIV-negative women, median plasma transferrin receptor concentrations were 24.4 and 24.1 nmol/l (P=0.5), respectively, and median plasma ferritin concentrations were 17.8 and 20.8 microg/l (P<0.05), respectively. There was a large overlap in plasma transferrin receptor concentrations among women with and without anemia. Using the combination of hemoglobin and ferritin as a standard, the sensitivity and specificity of plasma transferrin receptor in diagnosing iron deficiency anemia was estimated at 45.9% and 68.1%, respectively. CONCLUSION: The use of plasma transferrin receptor concentrations as an indicator of iron deficiency anemia may be limited in pregnant women with chronic inflammation and infection.