Rosemary Musonda

Why do young women have a much higher prevalence of HIV than young men? A study in Kisumu, Kenya and Ndola, Zambia

Objective: To examine the factors responsible for the disparity in HIV prevalence between young men and women in two urban populations in Africa with high HIV prevalence. Design: Cross-sectional survey, aiming to include 1000 men and 1000 women aged 15-49 years in Kisumu, Kenya and Ndola, Zambia. Methods: Participants were interviewed and tested for HIV and other sexually transmitted infections. Analyses compared the marital and non-marital partnership patterns in young men and women, and estimated the likelihood of having an HIV-infected partner. Results: Overall, 26% of individuals in Kisumu and 28% in Ndola were HIV-positive. In both sites, HIV prevalence in women was six times that in men among sexually active 15-19 year olds, three times that in men among 20-24 year olds, and equal to that in men among 25-49 year olds. Age at sexual debut was similar in men and women, and men had more partners than women. Women married younger than men and marriage was a risk factor for HIV, but the disparity in HIV prevalence was present in both married and unmarried individuals. Women often had older partners, and men rarely had partners much older than themselves. Nevertheless, the estimated prevalence of HIV in the partners of unmarried men aged under 20 was as high as that for unmarried women. HIV prevalence was very high even among women reporting one lifetime partner and few episodes of sexual intercourse. Conclusions: Behavioural factors could not fully explain the discrepancy in HIV prevalence between men and women. Despite the tendency for women to have older partners, young men were at least as likely to encounter an HIV-infected partner as young women. It is likely that the greater susceptibility of women to HIV infection is an important factor both in explaining the male-female discrepancy in HIV prevalence and in driving the epidemic. Herpes simplex virus type 2 infection, which is more prevalent in young women than in young men, is probably one of the factors that increases womens susceptibility to HIV infection.

Virologic and Immunologic Determinants of Heterosexual Transmission of Human Immunodeficiency Virus Type 1 in Africa

More than 80% of the worlds HIV-infected adults live in sub-Saharan Africa, where heterosexual transmission is the predominant mode of spread. The virologic and immunologic correlates of female-to-male (FTM) and male-to-female (MTF) transmission are not well understood. A total of 1022 heterosexual couples with discordant HIV-1 serology results (one partner HIV infected, the other HIV uninfected) were enrolled in a prospective study in Lusaka, Zambia and monitored at 3-month intervals. A nested case-control design was used to compare 109 transmitters and 208 nontransmitting controls with respect to plasma HIV-1 RNA (viral load, VL), virus isolation, and CD4(+) cell levels. Median plasma VL was significantly higher in transmitters than nontransmitters (123,507 vs. 51,310 copies/ml, p < 0.001). In stratified multivariate Cox regression analyses, the risk ratio (RR) for FTM transmission was 7.6 (95% CI: 2.3, 25.5) for VL > or = 100,000 copies/ml and 4.1 (95% CI: 1.2, 14.1) for VL between 10,000 and 100,000 copies/ml compared with the reference group of <10,000 copies/ml. Corresponding RRs for MTF transmission were 2.1 and 1.2, respectively, with 95% CI both bounding 1. Only 3 of 41 (7%) female transmitters had VL < 10,000 copies/ml compared with 32 of 93 (34%) of female nontransmitters (p < 0.001). The transmission rate within couples was 7.7/100 person-years and did not differ from FTM (61/862 person-years) and MTF (81/978 person-years) transmission. We conclude that the association between increasing plasma viral load was strong for female to male transmission, but was only weakly predictive of male to female transmission in Zambian heterosexual couples. FTM and MTF transmission rates were similar. These data suggest gender-specific differences in the biology of heterosexual transmission.

Hierarchical Targeting of Subtype C Human Immunodeficiency Virus Type 1 Proteins by CD8+ T Cells: Correlation with Viral Load

ABSTRACT An understanding of the relationship between the breadth and magnitude of T-cell epitope responses and viral loads is important for the design of effective vaccines. For this study, we screened a cohort of 46 subtype C human immunodeficiency virus type 1 (HIV-1)-infected individuals for T-cell responses against a panel of peptides corresponding to the complete subtype C genome. We used a gamma interferon ELISPOT assay to explore the hypothesis that patterns of T-cell responses across the expressed HIV-1 genome correlate with viral control. The estimated median time from seroconversion to response for the cohort was 13 months, and the order of cumulative T-cell responses against HIV proteins was as follows: Nef > Gag > Pol > Env > Vif > Rev > Vpr > Tat > Vpu. Nef was the most intensely targeted protein, with 97.5% of the epitopes being clustered within 119 amino acids, constituting almost one-third of the responses across the expressed genome. The second most targeted region was p24, comprising 17% of the responses. There was no correlation between viral load and the breadth of responses, but there was a weak positive correlation (r = 0.297; P = 0.034) between viral load and the total magnitude of responses, implying that the magnitude of T-cell recognition did not contribute to viral control. When hierarchical patterns of recognition were correlated with the viral load, preferential targeting of Gag was significantly (r = 0.445; P = 0.0025) associated with viral control. These data suggest that preferential targeting of Gag epitopes, rather than the breadth or magnitude of the response across the genome, may be an important marker of immune efficacy. These data have significance for the design of vaccines and for interpretation of vaccine-induced responses.

Declining HIV prevalence and risk behaviours in Zambia: evidence from surveillance and population-based surveys.

ObjectiveTo examine trends in HIV prevalence and behaviours in Zambia during the 1990s. MethodsThe core Zambian system for epidemiological surveillance and research has two major components: (i) HIV sentinel surveillance at selected antenatal clinics (ANC) in all provinces; and (ii) population-based HIV surveys in selected sentinel populations (1996 and 1999). The former was refined in 1994 to improve the monitoring of prevalence trends, whereas the latter was designed to validate ANC-based data, to study change in prevalence and behaviour concomitantly and to assess demographic impacts. ResultsThe ANC-based data showed a dominant trend of significant declines in HIV prevalence in the 15–19 years age-group, and for urban sites also in age-group 20–24 years and overall when rates were adjusted for over-representation of women with low education. In the general population prevalence declined significantly in urban women aged 15–29 years whereas it showed a tendency to decline among rural women aged 15–24 years. Prominent decline in prevalence was associated with higher education, stable or rising prevalence with low education. There was evidence in urban populations of increased condom use, decline in multiple sexual partners and, among younger women, delayed age at first birth. ConclusionsThe results suggested a dominant declining trend in HIV prevalence that corresponds to declines in incidence since the early 1990s attributable to behavioural changes. Efforts to sustain the ongoing process of change in the well-educated segments of the population should not be undervalued, but the modest change in behaviour identified among the most deprived groups represents the major preventive challenge.

The epidemiology of HSV-2 infection and its association with HIV infection in four urban African populations.

Objectives: To estimate age- and sex-specific herpes simplex virus type-2 (HSV-2) prevalence in urban African adult populations and to identify factors associated with infection. Design and methods: Cross-sectional, population-based samples of about 2000 adults interviewed in each of the following cities: Cotonou, Benin; Yaoundé, Cameroon; Kisumu, Kenya and Ndola, Zambia. Consenting study participants were tested for HIV, HSV-2 and other sexually transmitted infections. Results: HSV-2 prevalence was over 50% among women and over 25% among men in Yaoundé, Kisumu and Ndola, with notably high rates of infection among young women in Kisumu and Ndola (39% and 23%, respectively, among women aged 15-19 years). The prevalence in Cotonou was lower (30% in women and 12% in men). Multivariate analysis showed that HSV-2 prevalence was significantly associated with older age, ever being married, and number of lifetime sexual partners, in almost all cities and both sexes. There was also a strong, consistent association with HIV infection. Among women, the adjusted odds ratios for the association between HSV-2 and HIV infections ranged from 4.0 [95% confidence interval (CI) = 2.0-8.0] in Kisumu to 5.5 (95% CI = 1.7-18) in Yaoundé, and those among men ranged from 4.6 (95% CI = 2.7-7.7) in Ndola to 7.9 (95% CI = 4.1-15) in Kisumu. Conclusions: HSV-2 infection is highly prevalent in these populations, even at young ages, and is strongly associated with HIV at an individual level. At a population level, HSV-2 prevalence was highest in Kisumu and Ndola, the cities with the highest HIV rates, although rates were also high among women in Yaoundé, where there are high rates of partner change but relatively little HIV infection. The high prevalence of both infections among young people underlines the need for education and counselling among adolescents.

Ecological and individual level analysis of risk factors for HIV infection in four urban populations in sub-Saharan Africa with different levels of HIV infection

Objective: To identify factors that could explain differences in rate of spread of HIV between different regions in sub-Saharan Africa. Design: Cross-sectional study. Methods: The study took place in two cities with a relatively low HIV prevalence (Cotonou, Benin and Yaoundé, Cameroon), and two cities with a high HIV prevalence (Kisumu, Kenya and Ndola, Zambia). In each of these cities, a representative sample was taken of about 1000 men and 1000 women aged 15-49 years. Consenting men and women were interviewed about their socio-demographic background and sexual behaviour; and were tested for HIV, herpes simplex virus type 2 (HSV-2), syphilis, Chlamydia trachomatis and Neisseria gonorrhoea infection, and (women only) Trichomonas vaginalis. Analysis of risk factors for HIV infection was carried out for each city and each sex separately. Adjusted odds ratios (aOR) were obtained by multivariate logistic regression. Results: The prevalence of HIV infection in sexually active men was 3.9% in Cotonou, 4.4% in Yaoundé, 21.1% in Kisumu, and 25.4% in Ndola. For women, the corresponding figures were 4.0, 8.4, 31.6 and 35.1%. High-risk sexual behaviour was not more common in the high HIV prevalence cities than in the low HIV prevalence cities, but HSV-2 infection and lack of circumcision were consistently more prevalent in the high HIV prevalence cities than in the low HIV prevalence cities. In multivariate analysis, the association between HIV infection and sexual behavioural factors was variable across the four cities. Syphilis was associated with HIV infection in Ndola in men [aOR = 2.7, 95% confidence interval (CI) = 1.5-4.9] and in women (aOR = 1.7, 95% CI = 1.1-2.6). HSV-2 infection was strongly associated with HIV infection in all four cities and in both sexes (aOR ranging between 4.4 and 8.0). Circumcision had a strong protective effect against the acquisition of HIV by men in Kisumu (aOR = 0.25, 95% CI = 0.12-0.52). In Ndola, no association was found between circumcision and HIV infection but sample sizes were too small to fully adjust for confounding. Conclusion: The strong association between HIV and HSV-2 and male circumcision, and the distribution of the risk factors, led us to conclude that differences in efficiency of HIV transmission as mediated by biological factors outweigh differences in sexual behaviour in explaining the variation in rate of spread of HIV between the four cities.

Studying dynamics of the HIV epidemic: population-based data compared with sentinel surveillance in Zambia.

Objectives:To establish population-based HIV survey data in selected populations, and to assess the validity of extrapolation from HIV sentinel surveillance amongst antenatal clinic attenders (ANC) to the general population. Methods:In a population survey, adults aged ≥ 15 years were selected by stratified random cluster sampling (n = 4195). The survey was carried out in catchment populations of clinics used for national HIV surveillance. The methodology allows detailed comparisons of HIV infection patterns to be made in two areas (urban and rural). Whereas the sentinel surveillance used serum-based HIV testing, the population survey used saliva (93.5% consented to provide a saliva sample). Results:Surveillance of ANC tended to underestimate the overall HIV prevalence of the general population, but differences were not statistically significant. In the urban area, the adjusted overall HIV prevalence rate of ANC (aged 15–39 years) was 24.4% [95% confidence interval (CI), 20.9–28.0] compared with 26.0% (95% CI, 23.4–28.6) in the general population. The respective rural estimates were 12.5% (95% CI, 9.3–15.6) versus 16.4% (95% CI, 12.1–20.6). Age-specific prevalence rates showed ANC to overestimate infection in teenagers (aged 15–19 years), whereas in the reverse direction of those aged ≥ 30 years. Teenagers analysed by single year of age revealed both ANC and women in the general population with about the same steep increase in prevalence by age, but the former at consistently higher rates. Extrapolations might be biased substantially due to the higher pregnancy rates amongst uninfected individuals. Conclusions:ANC-based data might draw a rather distorted picture of current dynamics of the HIV epidemic. Even though representing an obvious oversimplification, extrapolations of overall prevalence rates may correlate with that of the general population.

Multicentre study on factors determining differences in rate of spread of HIV in sub-Saharan Africa: methods and prevalence of HIV infection

Objective: The objective of this study was to explore whether the differences in rate of spread of HIV in different regions in sub-Saharan Africa could be explained by differences in sexual behaviour and/or factors influencing the probability of HIV transmission during sexual intercourse. Methods: A cross-sectional, population-based study was conducted in two cities with a high HIV prevalence (Kisumu in Kenya and Ndola in Zambia) and two cities with a relatively low HIV prevalence (Cotonou in Benin and Yaoundé in Cameroon). In each of these cities, approximately 1000 men and 1000 women, aged 15-49 years, were randomly selected from the general population. Consenting men and women were interviewed and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection and trichomoniasis (the latter for women only). In addition, a survey was conducted on a random sample of 300 sex workers in each city. The research instruments, including the questionnaires and the laboratory procedures, were standardized to permit comparison of results. Results: The numbers of men interviewed were 1021 in Cotonou, 973 in Yaoundé, 829 in Kisumu, and 720 in Ndola. The corresponding figures for women were 1095, 1116, 1060 and 1130. In Yaoundé, Kisumu and Ndola, the response rates for men were lower than for women due to failure to make contact with eligible men. The proportion of eligible women who were interviewed was 86% in Yaoundé, and 89% in Kisumu and Ndola. In Yaoundé, 76% of eligible men were interviewed, along with 82% in Kisumu and 75% in Ndola. The prevalence of HIV infection in men was 3.3% in Cotonou, 4.1% in Yaoundé, 19.8% in Kisumu and 23.2% in Ndola. For women, the respective figures were 3.4, 7.8, 30.1 and 31.9%. The prevalence of HIV infection among women aged 15-19 years was 23.0% in Kisumu and 15.4% in Ndola. Among women in Kisumu who had their sexual debut 5 years before the interview, the prevalence of HIV infection was 46%; in Ndola, it was 59%. Among sex workers, the prevalence of HIV infection was 57.5% in Cotonou, 34.4% in Yaoundé, 74.7% in Kisumu and 68.7% in Ndola. Conclusions: The HIV prevalence rates in the general population confirmed our preliminary assessment of the level of HIV infection in the four cities, which was based on estimates of HIV prevalence from sentinel surveillance among pregnant women. The very high prevalence of HIV infection among young women in Kisumu and Ndola calls for urgent intervention.

Simplified strategy for detection of recombinant human immunodeficiency virus type 1 group M isolates by gag/env heteroduplex mobility assay

We developed a heteroduplex mobility assay in the gag gene (gag HMA) for the identification of group M subtypes A to H. The assay covers the region coding for amino acid 132 of p24 to amino acid 20 of p7 (according to human immunodeficiency virus type 1 [HIV-1] ELI, 460 bp). The gag HMA was compared with sequencing and phylogenetic analysis of an evaluation panel of 79 HIV-1 group M isolates isolated from infected individuals from different geographic regions. Application of gag HMA in combination with env HMA on 252 HIV-1- positive plasma samples from Bénin, Cameroon, Kenya, and Zambia revealed a high prevalence of a variety of intersubtype recombinants in Yaoundé, Cameroon (53.8%); Kisumu, Kenya (26.8%); and Cotonou, Bénin (41%); no recombinants were identified among the samples from Ndola, Zambia. The AG(IbNG) circulating recombinant form, as determined by gag HMA, was found to be the most common intersubtype recombinant in Yaoundé (39.4%) and Cotonou (38.5%). Using a one-tube reverse transcriptase PCR protocol, this gag HMA in combination with env HMA is a useful tool for rapidly monitoring the prevalence of the various genetic subtypes as well as of recombinants of HIV-1. Moreover, this technology can easily be applied in laboratories in developing countries.ABSTRACT We developed a heteroduplex mobility assay in the gaggene (gag HMA) for the identification of group M subtypes A to H. The assay covers the region coding for amino acid 132 of p24 to amino acid 20 of p7 (according to human immunodeficiency virus type 1 [HIV-1] ELI, 460 bp). Thegag HMA was compared with sequencing and phylogenetic analysis of an evaluation panel of 79 HIV-1 group M isolates isolated from infected individuals from different geographic regions. Application of gag HMA in combination with envHMA on 252 HIV-1- positive plasma samples from Bénin, Cameroon, Kenya, and Zambia revealed a high prevalence of a variety of intersubtype recombinants in Yaoundé, Cameroon (53.8%); Kisumu, Kenya (26.8%); and Cotonou, Bénin (41%); no recombinants were identified among the samples from Ndola, Zambia. The AGIbNG circulating recombinant form, as determined bygag HMA, was found to be the most common intersubtype recombinant in Yaoundé (39.4%) and Cotonou (38.5%). Using a one-tube reverse transcriptase PCR protocol, this gag HMA in combination with env HMA is a useful tool for rapidly monitoring the prevalence of the various genetic subtypes as well as of recombinants of HIV-1. Moreover, this technology can easily be applied in laboratories in developing countries.

The HIV epidemic in Zambia : socio-demographic prevalence patterns and indications of trends among childbearing women

Objective:To examine socio-demographic HIV prevalence patterns and trends among childbearing women in Zambia. Design:Repeated cross-sectional surveys. Methods:Personal interviews and unlinked anonymous testing of blood samples of women attending antenatal care in selected areas. Results:The 1994 data includes information from 27 areas and a total of 11 517 women. The HIV prevalence among urban residents appeared with moderate variation at a very high level (range 25–32%, comparing provinces). The geographical variation was more prominent in rural populations (range 8–16%) and was approximately half the prevalence level of the urban populations. With the exception of the 15–19 years age-group, HIV infection was found to rise sharply with increasing educational attainment (odds ratio, 3.1; confidence interval, 2.6–3.8) when contrasting extreme educational levels. Although the assessment of trends is somewhat restricted, the available information indicates stable prevalence levels in most populations over the last 2–4 years. Conclusions:The data showed extremely high HIV prevalence levels among childbearing women. Longer time-intervals between surveys are needed, however, in order to verify the stability in prevalence identified by this study. The tendency to changing differentials by social status is suggested as a possible sign of an ongoing process of significant behavioural change.