(See the editorial commentary by Branson and Stekler, on pages 521–4.)
Background. Most human immunodeficiency virus (HIV) point-of-care tests detect antibodies (Ab) but not p24 antigen (Ag) or RNA. In the absence of antibodies, p24 antigen and RNA typically indicate acute HIV infection. We conducted a field evaluation of the Determine® HIV-1/2 Ag/Ab Combo rapid test (Combo RT).
Methods. The antigen portion of the Combo RT (for acute HIV infection) was compared with a Roche Monitor HIV RNA polymerase chain reaction assay. The antibody portion of Combo RT (for established HIV infection) was compared with rapid test algorithms. Participants were enrolled at a sexually transmitted infection clinic and HIV testing and counseling center in Lilongwe, Malawi. Rapid testing was conducted with parallel testing in the clinic and serial testing in the center. The Combo RT was performed in clinic participants with negative or discordant antibody results and in all center participants.
Results. Of the participants 838 were HIV negative, 163 had established HIV infection, and 8 had acute HIV infection. For detecting acute HIV infection, the antigen portion had a sensitivity of 0.000 and a specificity of 0.983. For detecting established HIV infection, the antibody portion had a sensitivity of 0.994 and a specificity of 0.992.
Conclusions. Combo RT displayed excellent performance for detecting established HIV infection and poor performance for detecting acute HIV infection. In this setting, Combo RT is no more useful than current algorithms.
Concurrent sexual partnerships are believed to play an important role in HIV transmission in sub-Saharan Africa, but the contributions of concurrency to HIV and STI spread depend on the details of infectious periods and relationship patterns. To contribute to the understanding of sexual partnership patterns in this region, we estimated partnership lengths, temporal gaps between partners, and periods of overlap across partners at an STI clinic in Lilongwe, Malawi.
Participants underwent physical examinations and HIV tests, and responded to questionnaires about demographics and risk behaviors, including detailed questions about a maximum of 3 sexual partners in the previous 2 months. We calculated partnership length as the time between the first and most recent sexual contact with a partner, and gap length as the time between the most recent contact with one partner and the first contact with the next. We defined concurrent and consecutive partnerships as gap length≤0 days and gap length>0 days, respectively.
The study population (n=183) had a mean partnership length of 858 days (median=176 days). Eighty-six percent reported 0 or 1 partner, 5% reported multiple consecutive partnerships, and 9% reported concurrency. Gaps between consecutive partnerships were short (mean=21 days), and overlaps across concurrent partners tended to be long (mean=246 days).
Multiple sexual partnerships were uncommon, and partnerships were long on average. Among those reporting multiple recent partners, both long-term concurrency and narrowly spaced consecutive partnerships could present substantial risk for efficient transmission of HIV and classical STIs.
Transmission; concurrency; partnership length; gap length; overlap
To determine the safety and effectiveness of BufferGel and 0.5% PRO2000 microbicide gels for the prevention of male to female HIV transmission
Phase II/IIb, randomized, placebo-controlled trial with three double-blinded gel arms and an open label no gel arm.
Study participants from Malawi, South Africa, Zambia, Zimbabwe and USA were instructed to apply study gel ≤1 hour before each sex act and safety, sexual behavior, pregnancy, gel adherence, acceptability, and HIV serostatus were assessed during follow-up.
The 3101 enrolled women were followed for an average of 20.4 months with 93.6% retention and 81.1% self-reported gel adherence. Adverse event rates were similar in all study arms. HIV incidence rates in the 0.5% PRO2000 Gel, BufferGel, Placebo Gel and No Gel arms were 2.70, 4.14, 3.91 and 4.02 per 100 women-years, respectively. HIV incidence in the 0.5% PRO2000 Gel arm was lower than the Placebo Gel arm (Hazard Ratio (HR)=0.7; p=0.10) and the No Gel arm (HR=0.67; p=0.06). HIV incidence rates were similar in the BufferGel and both Placebo Gel (HR=1.10; p=0.63) and No Gel control arms (HR=1.05; p=0.78). HIV incidence was similar in the Placebo Gel and No Gel arms (HR=0.97; p=0.89).
0.5% PRO2000 Gel demonstrated a modest 30% reduction in HIV acquisition in women. However, these results were not statistically significant and subsequent findings from the MDP 301 trial have confirmed that 0.5% PRO2000 has little or no protective effect. BufferGel did not alter the risk of HIV infection. Both products were safe.
Microbicide; PRO 2000 Gel; BufferGel; HIV Prevention; Women
Sexual partners of persons with newly diagnosed HIV infection require HIV counseling, testing and, if necessary, evaluation for therapy. However, many African countries do not have a standardized protocol for partner notification and the effectiveness of partner notification has not been evaluated in developing countries.
Individuals with newly diagnosed HIV infection presenting to STI clinics in Lilongwe, Malawi were randomized to one of three methods of partner notification: passive referral, contract referral, or provider referral. The passive referral group was responsible for notifying their partners themselves. The contract referral group was given seven days to notify their partners, after which a health care provider contacted partners who had not reported for counseling and testing. In the provider referral group, a health care provider notified partners directly.
240 index patients named 302 sexual partners and provided locator information for 252. Among locatable partners, 107 returned for HIV counseling and testing; 20/82 (24%; 95% CI 15 – 34%) partners returned in the passive referral arm, 45/88 (51%; 95% CI 41 – 62%) in the contract referral arm, and 42/82 (51%; 95% CI 40 – 62%) in the provider referral arm (p<0·001). Among returning partners (n=107), 67 (64%) of were HIV-infected with 54 (81%) newly diagnosed.
This study provides the first evidence of the effectiveness of partner notification in sub-Saharan Africa. Active partner notification was feasible, acceptable, and effective among STI clinic patients. Partner notification will increase early referral to care and facilitate risk reduction among high-risk uninfected partners.
Partner notification; HIV counseling and testing; sub-Saharan Africa
Life-threatening infections present major challenges for health systems in Malawi and the developing world because routine microbiologic culture and sensitivity testing are not performed due to lack of capacity. Use of empirical antimicrobial therapy without regular microbiologic surveillance is unable to provide adequate treatment in the face of emerging antimicrobial resistance. This study was conducted to determine antimicrobial susceptibility patterns in order to inform treatment choices and generate hospital-wide baseline data.
Culture and susceptibility testing was performed on various specimens from patients presenting with possible infectious diseases at Kamuzu Central Hospital, Lilongwe, Malawi.
Between July 2006 and December 2007 3104 specimens from 2458 patients were evaluated, with 60.1% from the adult medical service. Common presentations were sepsis, meningitis, pneumonia and abscess. An etiologic agent was detected in 13% of patients. The most common organisms detected from blood cultures were Staphylococcus aureus, Escherichia coli, Salmonella species and Streptococcus pneumoniae, whereas Streptococcus pneumoniae and Cryptococcus neoformans were most frequently detected from cerebrospinal fluid. Haemophilus influenzae was rarely isolated. Resistance to commonly used antibiotics was observed in up to 80% of the isolates while antibiotics that were not commonly in use maintained susceptibility.
There is widespread resistance to almost all of the antibiotics that are empirically used in Malawi. Antibiotics that have not been widely introduced in Malawi show better laboratory performance. Choices for empirical therapy in Malawi should be revised accordingly. A microbiologic surveillance system should be established and prudent use of antimicrobials promoted to improve patient care.
Injury is a major cause of morbidity and mortality in developing countries. Utilizing a partnership between Kamuzu Central Hospital (KCH) and the University of North Carolina Departments of Surgery, we describe an approach to injury surveillance, examine the utility of trauma scoring systems, and outline steps necessary before such scoring systems can be reliably instituted in a resource-constrained setting.
HIV transmission risk during acute and early HIV infection (EHI) is sharply elevated, but the contribution of EHI to ongoing HIV transmission is controversial. However, in settings where EHI contributes substantially to secondary transmissions, early diagnosis and intervention may be critical for HIV prevention. We estimated the contribution of EHI to HIV incidence in Lilongwe, Malawi and predicted the future impact of hypothetical prevention interventions affecting EHI only, chronic HIV infection (CHI) only, or both stages.
We developed a deterministic mathematical model describing heterosexual HIV transmission, informed by detailed behavioural and viral load data collected in Lilongwe. We included sexual contact within and outside steady pairs and divided the infectious period into multiple intervals to allow for changes in transmissibility by infection stage. We used a Bayesian melding approach to fit the model to HIV prevalence data collected over time at Lilongwe antenatal clinics. We evaluated interventions that reduced the per-contact transmission probability to 0·00003 in those receiving them and varied the proportion of individuals receiving the intervention in each stage.
We estimated that 38·4% (95% credible interval: 18·6%-52·3%) of ongoing HIV transmissions in Lilongwe are attributable to sexual contact with EHI index cases. Interventions acting only during EHI substantially reduced HIV prevalence, but did not lead to elimination, even with 100% coverage. Interventions acting only during CHI also reduced HIV prevalence, but coverage levels of 95%-99% were required to move the epidemic toward elimination. In scenarios with <95% CHI coverage, additional interventions reaching 25%-75% of EHI cases reduced HIV prevalence substantially.
Our results suggest that EHI plays an important role in HIV transmission in this sub-Saharan African setting. Without near-perfect coverage, interventions during CHI will likely have incomplete effectiveness unless complemented by strategies targeting the heightened transmission risk of EHI.
Assess population attributable fractions (PAFs) for late postnatal transmission (LPT) of human immunodeficiency virus-1 (HIV-1) in a cohort of HIV-1-exposed infants.
We used data established from a risk factor analysis of LPT (negative HIV-1 results through the 4-6 week visit, but positive assays thereafter through the 12-month visit) from a perinatal clinical trial conducted in three sub-Saharan countries. PAFs were calculated as the proportions of excess LPTs attributed to identified risk factors.
For the cohort of 1317 infants, 206 (15.6%) had only low maternal CD4+ counts (< 200 cells/mm3), 332 (25.2%) had only high maternal plasma viral loads (VLs) (> 50 000 copies/mL), and 81 (6.2%) had both low CD4+ counts and high VLs. Their PAFs were 26.0% [95% confidence interval (CI), 12.0%-36.0%], 37.0% (95% CI, 22.0%-51.0%) and 16.0% (95% CI, 6.0%-25.0%), respectively.
Our PAF analysis illustrates the public health impact of the substantial proportion of LPTs accounted for by high-risk women with both low CD4+ counts and high VLs. In light of these results, access to and use of antiretroviral therapy (ART) by high-risk HIV-1-infected pregnant women is essential. Additional strategies to reduce LPT for those not meeting criteria for ART should be implemented.
Breast feeding; late postnatal transmission; prevention of mother to child transmission/vertical transmission; risk factors; viral load
We examined the association of individual demographic and behavioral attributes, partnership (dyad) and social network characteristics with unprotected sex in the heterosexual dyads of IDUs in St Petersburg, Russia. Of the individual-level characteristics female gender and younger age; and of the dyad-level characteristics sharing injecting equipment, social exposure to the sex partner (“hanging out with” or seeing each other daily), and both partners self-reporting being HIV infected were associated with unprotected sex. Although self-reported HIV discordant couples were less likely to engage in unprotected sex, it was reported in over half of self-reported HIV discordant relationships. This study highlights the intertwining of sexual risk and injecting risk, and the importance of sero-sorting based on perceived HIV status among IDU sexual partnerships in St Petersburg, Russia. A combination of social network and dyad interventions may be appropriate for this population of IDUs, especially for IDUs who are both injecting and sex partners, supported by free and confidential rapid HIV testing and counseling services to provide a comprehensive response to the wide-spread HIV epidemic among IDUs in St Petersburg.
Injecting drug users; Risk networks; Sexual risk; HIV infection risk; Dyad analysis; Russia
In this study, we investigated how individual attributes, dyad characteristics and social network characteristics may influence engaging in receptive syringe sharing, distributive syringe sharing and sharing cookers in injecting partnerships of IDUs in St Petersburg, Russia. We found that all three levels were associated with injecting equipment sharing, and that dyad characteristics were modified by characteristics of the social network. Self-reported HIV discordance and male gender concordance played a role in the risk of equipment sharing. Dyad interventions may not be sufficient to reduce injecting risk in IDU partnerships, but a combination of dyad and network interventions that target both IDU partnerships and the entire IDU population may be more appropriate to address injecting risk among IDUs.
Injecting drug users; Risk networks; Injecting risk; Dyad analysis; Russia
To assess among injecting drug users (IDUs) in St Petersburg, Russia, the urban environmental, social norms, and individual correlates of unsafe injecting.
Between December 2004 and January 2007 IDUs (N=446) were interviewed in St. Petersburg, Russia.
Prevalence of HCV was 96% and HIV 44%; 17% reported receptive syringe sharing after an HIV infected IDU (RSS); 49% distributive syringe sharing (DSS); 76% sharing cookers, 73% sharing filters and 71% syringe mediated drug sharing (SMS) when not all syringes were new. Urban environmental characteristics correlated with sharing cookers and SMS; and social norms correlated with RSS, DSS and sharing cookers. Individual correlates included cleaning used syringes (all five dependent variables) and self-report of HIV infection (RSS and DSS).
HIV status disclosure is an unreliable but frequently used HIV prevention method among IDUs in St. Petersburg, who reported alarmingly high levels of injecting equipment sharing. Voluntary counseling and testing should be widely available for this population. Ethnography is needed to assess the effectiveness of the syringe cleaning process. Prevention interventions need to be ongoing among IDUs in St. Petersburg, and should incorporate urban environmental factors and social norms, which may involve peer education and social network interventions.
Russia; Injecting drug users; Injecting equipment sharing; HIV infection; Hepatitis infections
The HIV/AIDS epidemic in St Petersburg, as in much of Russia, is concentrated among injection drug users (IDU) in whom prevalence reached 30% in 2003. Understanding the dynamics of the epidemic is important in developing appropriate responses in the resource-constrained context of Russian cities such as St Petersburg.
IDU were contacted and screened to create a seronegative cohort for prevention and vaccine studies. At screening, individuals provided sociodemographic, drug use, and injection and sex-related risk behavior data. Seronegative individuals who enrolled in the cohort were followed for one year and tested for HIV semiannually. Residential addresses were entered into a geographical information system programme and analysed for spatial clustering using Moran’s I and nearest-neighbor analysis.
We mapped 788 of the 900 study participants to discrete locations within St Petersburg; 236 (29.9%) were HIV seropositive at baseline. Although there was no clustering of the study population as a whole, HIV-infected individuals were tightly clustered and prevalence co-clustered with high frequency of heroin injection, receptive syringe sharing, being younger than 24 years, and living with parents. These clusters were restricted to 5% of populated areas of the city. We mapped 18 of 20 incident cases detected among the cohort, and more than half were located within or adjacent to the clusters.
Spatial analysis identified linkages between disease prevalence and risky injection behaviors that were not evident using traditional epidemiological analysis. The analysis also identified where resources might be allocated geographically for maximum impact in slowing the HIV epidemic among IDU.
geographical information systems; harm reduction; HIV/AIDS; injection drug use
To determine the optimal time for a second HIV-1 nucleic acid amplification assay to detect late postnatal transmission of HIV-1 (first negative test at 4–8 weeks of age) in resource limited settings.
A longitudinal analysis of data from HPTN 024
Children born to HIV-1 infected mothers enrolled in the HIV Prevention Trial Network trial 024 (HPTN 024) were tested for HIV-1 infection at six intervals within the first year of life. Mothers and infants received nevirapine prophylaxis. We estimated the probability of being alive and having a positive test in each interval after 4–8 weeks and at 30 days post-weaning, conditional on having acquired HIV during the late postnatal period. The interval with the highest probability was taken to be the optimal visit interval.
A total of 1609 infants from HPTN 024 had at least one HIV-1 diagnostic test and were included in the analysis. We found that testing at one month after weaning or 12 months of age (whichever comes first), identified 81% of those infected during the late postnatal period (after 4–8 weeks) through breastfeeding. In total, 93% (95% CI: 89,98) of all infected infants would be detected if tests were performed at these two time points.
In resource-limited settings, HIV-1 PCR testing at 4–8 weeks followed by a second test at one month after weaning or at one year of age (whichever comes first), led to the identification of the vast majority of HIV-1 infected infants.
HIV infant diagnosis; late postnatal transmission; breast feeding
The objectives of this cross-sectional study were to determine correlates of syphilis seroprevalence among HIV-infected and -uninfected antenatal attendees in an African multisite clinical trial, and to improve strategies for maternal syphilis prevention.
A total of 2270 (86%) women were HIV-infected and 366 (14%) were HIV-uninfected. One hundred seventy-five (6.6%) were syphilis-seropositive (7.3% among HIV-infected and 2.6% HIV-uninfected women). Statistically significant correlates included geographic site (odds ratio [OR] = 4.5, Blantyre; OR = 3.2, Lilongwe; OR = 9.0, Lusaka vs. Dar es Salaam referent); HIV infection (OR = 3.3); age 20 to 24 years (OR = 2.5); being divorced, widowed, or separated (OR = 2.9); genital ulcer treatment in the last year (OR = 2.9); history of stillbirth (OR = 2.8, one stillbirth; OR = 4.3, 2–5 stillbirths); and history of preterm delivery (OR = 2.7, one preterm delivery).
Many women without identified risk factors were syphilis-seropositive. Younger HIV-infected women were at highest risk. Universal integrated antenatal HIV and syphilis screening and treatment is essential in sub-Saharan African settings.
The HIV epidemic in Russia has been driven by the unsafe injection of drugs, predominantly heroin and the ephedrine derived psychostimulants. Understanding differences in HIV risk behaviors among injectors associated with different substances has important implications for prevention programs.
We examined behaviors associated with HIV risk among 900 IDUs who inject heroin, psychostimulants, or multiple substances in 2002. Study participants completed screening questionnaires that provided data on sociodemographics, drug use, place of residence and injection- and sex-related HIV risk behaviors. HIV testing was performed and prevalence was modeled using general estimating equation (GEE) analysis. Individuals were clustered by neighborhood and disaggregated into three drug use categories: Heroin Only Users, Stimulant Only Users, and Mixed Drug Users.
Among Heroin Only Users, younger age, front/backloading of syringes, sharing cotton and cookers were all significant predictors of HIV infection. In contrast, sharing needles and rinse water were significant among the Stimulant Only Users. The Mixed Drug Use group was similar to the Heroin Only Users with age, front/back loading, and sharing cotton significantly associated with HIV infection. These differences became apparent only when neighborhood of residence was included in models run using GEE.
The type of drug injected was associated with distinct behavioral risks. Risks specific to Stimulant Only Users appeared related to direct syringe sharing. The risks specific to the other two groups are common to the process of sharing drugs in preparation to injecting. Across the board, IDUs could profit from prevention education that emphasizes both access to clean syringes and preparing and apportioning drug with these clean syringes. However, attention to neighborhood differences might improve the intervention impact for injectors who favor different drugs.
Individuals with acute (preseroconversion) HIV infection (AHI) are important in the spread of HIV. The identification of AHI requires the detection of viral proteins or nucleic acids with techniques that are often unaffordable for routine use. To facilitate the efficient use of these tests, we sought to develop a risk score algorithm for identifying likely AHI cases and targeting the tests towards those individuals.
A cross-sectional study of 1448 adults attending a sexually transmitted infections (STI) clinic in Malawi.
Using logistic regression, we identified risk behaviors, symptoms, HIV rapid test results, and STI syndromes that were predictive of AHI. We assigned a model-based score to each predictor and calculated a risk score for each participant.
Twenty-one participants (1.45%) had AHI, 588 had established HIV infection, and 839 were HIV-negative. AHI was strongly associated with discordant rapid HIV tests and genital ulcer disease (GUD). The algorithm also included diarrhea, more than one sexual partner in 2 months, body ache, and fever. Corresponding predictor scores were 1 for fever, body ache, and more than one partner; 2 for diarrhea and GUD; and 4 for discordant rapid tests. A risk score of 2 or greater was 95.2% sensitive and 60.5% specific in detecting AHI.
Using this algorithm, we could identify 95% of AHI cases by performing nucleic acid or protein tests in only 40% of patients. Risk score algorithms could enable rapid, reliable AHI detection in resource-limited settings.
acute HIV infection; detection; diagnosis; risk score algorithm; screening
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.
semen; HIV transmission; acute HIV infection; peak viral load
We have examined the nature of V3 sequence variability among subtype C human immunodeficiency virus type 1 (HIV-1) sequences from plasma-derived viral RNA present in infected men from Malawi. Sequence variability was assessed by direct sequence analysis of the V3 reverse transcription-PCR products, examination of virus populations by a subtype C V3-specific heteroduplex tracking assay (V3-HTA), and selected sequence analysis of molecular clones derived from the PCR products. Sequence variability in V3 among the subtype C viruses was not associated with the presence of basic amino acid substitutions. This observation is in contrast to that for subtype B HIV-1, where sequence variability is associated with such substitutions, and these substitutions are determinants of altered coreceptor usage. Evolutionary variants in subtype C V3 sequences, as defined by the V3-HTA, were not correlated with the CD4 level in the infected person, while such a correlation was found with subtype B V3 sequences. Viruses were isolated from a subset of the subjects; all isolates used CCR5 and not CXCR4 as a coreceptor, and none was able to grow in MT-2 cells, a hallmark of the syncytium-inducing phenotype that is correlated with CXCR4 usage. The overall sequence variability of the subtype C V3 region was no greater than that of the conserved regions of gp120. This limited sequence variability was also a feature of subtype B V3 sequences that do not carry the basic amino acid substitutions associated with altered coreceptor usage. Our results indicate that altered coreceptor usage is rare in subtype C HIV-1 isolates in sub-Saharan Africa and that sequence variability is not a feature of the V3 region of env in the absence of altered coreceptor usage.
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.)
HIV incidence is higher among pregnant women than their non-pregnant counterparts in some sub-Saharan African settings. Our aims were (1) to estimate HIV incidence during pregnancy and (2) to compare sexual activity between pregnant, postpartum, and non-pregnant women.
We examined a retrospective cohort of 1087 women to identify seroconverters using antenatal and labor ward HIV test results. We also conducted a cross-sectional survey, including a quantitative questionnaire (n = 200) and in-depth interviews (n = 20) among women in early pregnancy, late pregnancy, postpartum, and non-pregnancy. Outcomes included measures of sexual activity, reported spouse’s risky behavior, and beliefs about abstinence.
11 of 1087 women seroconverted during pregnancy yielding a 1% seroconversion risk and an incidence rate of 4.0/100 person years (95% CI 2.2–7.2). The reported sexual activity of the early pregnancy and non-pregnancy groups was similar, but significantly higher than the late pregnancy and postpartum groups (p<0.001). During pregnancy, sex acts decreased as gestation increased (p = 0.001). There was no reported difference in the spouse’s risky behavior. Most women believed that sex should cease between the 6th and 8th month of pregnancy and should not resume until 6 months postpartum. Some talked about conflict between their cultural obligation to abstain and fear of HIV infection if their spouses find other partners.
HIV incidence is high among pregnant women in Malawi, and sexual activity decreases during pregnancy and postpartum. Pregnant women need to be informed of their increased risk for HIV and the importance of using condoms throughout pregnancy and the postpartum period.
Injury surveillance is an ongoing process required for primary, secondary, and tertiary injury prevention. In Malawi, hospital-based injury data are not available.
From February to June 2008 we collected data on injured patients presenting to Kamuzu Central Hospital in Lilongwe, Malawi. The sample (n = 1,474) was predominantly male (75.7%), and age distribution was bimodal (peak age groups <5 years and 26–30 years). Road-traffic injury (RTI) was the most common reason for treatment (43.4%), followed by assault (24.0%), which was more common than expected. The most common injuries were lacerations, contusions, and abrasions. We observed both gender- and age-specific patterns in injury mechanism: Injured females were more likely than injured males to have suffered an injury as a passenger in a car or on a bicycle, or to have suffered from falls, foreign bodies, and burns; injured males were more likely than injured females to have suffered an injury as an automobile driver or bicyclist, or from an assault. Falls, burns, and foreign bodies affected younger victims, whereas bicyclists, automobile drivers, and motorcycle operators were generally older persons.
The hospital admission rate was 26.8%. Most patients arrived by private vehicle (43.8%), which was also the fastest means of transportation. There were 25 mass casualties leading to 102 admissions; all but one were due to RTIs, and seven were associated with at least one fatality.
This study elucidated injury epidemiology in Malawi and identified questions for future research. Other developing countries should conduct such prospective data collection to identify region-specific injury patterns and to promote injury prevention.
Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples.
In nine countries, we enrolled 1763 couples in which one partner was HIV-1–positive and the other was HIV-1–negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1–infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1–related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1–negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death.
As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P = 0.01).
The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy.
A randomized controlled trial in South Africa found a beneficial effect of acyclovir on genital ulcer healing, but no effect was seen in trials in Ghana, Central African Republic and Malawi. The aim of this paper is to assess whether the variation in impact of acyclovir on ulcer healing in these trials can be explained by differences in the characteristics of the study populations.
Pooled data were analysed to estimate the impact of acyclovir on the proportion of ulcers healed seven days after randomisation by HIV/CD4 status, ulcer aetiology, size and duration before presentation; and impact on lesional HIV-1. Risk ratios (RR) were estimated using Poisson regression with robust standard errors. Of 1478 patients with genital ulcer, most (63%) had herpetic ulcers (16% first episode HSV-2 ulcers), and a further 3% chancroid, 2% syphilis, 0.7% lymphogranuloma venereum and 31% undetermined aetiology. Over half (58%) of patients were HIV-1 seropositive. The median duration of symptoms before presentation was 6 days. Patients on acyclovir were more likely to have a healed ulcer on day 7 (63% vs 57%, RR = 1.08, 95% CI 0.98–1.18), shorter time to healing (p = 0.04) and less lesional HIV-1 RNA (p = 0.03). Small ulcers (<50 mm2), HSV-2 ulcers, first episode HSV-2 ulcers, and ulcers in HIV-1 seropositive individuals responded best but the better effectiveness in South Africa was not explained by differences in these factors.
There may be slight benefit in adding acyclovir to syndromic management in settings where most ulcers are genital herpes. The stronger effect among HIV-1 infected individuals suggests that acyclovir may be beneficial for GUD/HIV-1 co-infected patients. The high prevalence in this population highlights that genital ulceration in patients with unknown HIV status provides a potential entry point for provider-initiated HIV testing.