Sociodemographic factors associated with participation by HIV-1-positive pregnant women in an intervention to prevent mother-to-child transmission of HIV in Cote d'Ivoire.

Many HIV-1-seropositive women in Africa who are offered antiretroviral prophylaxis to prevent mother-to-child transmission (MTCT) of HIV do not begin interventions. Research on barriers to participation has not addressed the possible effects of women's sociocultural and economic circumstances. We examined these factors at an MTCT prevention programme in Abidjan, Cote d'Ivoire. We interviewed two groups of women after they had received HIV-positive test results and had been invited by the programme staff to return for monthly follow-up visits before beginning short-course zidovudine prophylaxis. Participants (n = 30) completed follow-up visits and prophylaxis. Non-participants (n = 27) refused or discontinued follow-up visits and did not begin zidovudine. Fewer non-participants had been born in Cote d'Ivoire (67% vs. 97%) or were Ivorian nationals (48% vs. 77%); they had lived in the country for less time (21 vs. 26 median years). They were less likely to be French-literate (37% vs. 77%), and more of them reported having had Koranic education only (18% vs. 0). They more often reported miscarriages, stillbirths, or infant deaths (69% vs. 33%), and had partners with low-ranked jobs (63% vs. 30%). Our findings suggest that the non-participants were more marginal socioculturally and economically in Ivorian society than participants. Greater attention to mitigating the effects of broader structural factors on women's participation in interventions may increase the effectiveness of MTCT prevention in Africa.

Lower HIV-2 plasma viral loads may explain differences between the natural histories of HIV-1 and HIV-2 infections.

To explain the low transmissibility and pathogenicity of HIV-2 infection's plasma viral loads in both HIV-1- and HIV-2-infected persons were compared by using the polymerase chain reaction (PCR)-based Amp-RT assay to measure levels of reverse transcriptase (RT) activity. The study comprised a total of 155 HIV-infected-people including 58 who were infected with HIV-2 with CD4+ cell counts <500 x 106/L (n = 15), CD4+ cell counts >500 x 106/L (n = 26), or with tuberculosis (TB; n = 17), and 97 HIV-1-infected people with CD4+ cell counts <500 x 106/L (n = 32), CD4+ cell counts >500 x 106/L (n = 25), or TB (n = 40). Among persons with CD4+ cell counts <500 x 106/L, 11 (73.3%) of 15 HIV-2-infected persons had detectable plasma RT activity compared with 25 (78.1%) of 32 HIV-1-infected persons (p =.725). However, the median HIV-2 plasma RT activity in this group was significantly lower (2561 x 10-10 U/ml; p =.036; detectable range, 1712-644,868 x 10-10 U/ml) than the RT activity of HIV-1-infected persons with similar CD4+ cell counts (13,241 x 10-10 U/ml; detectable range, 8482-1,478,880 x 10-10 U/ml). Among TB patients, 10 (58.8%) of 17 HIV-2-infected persons had detectable plasma RT activity compared with 30 (75%) of 40 HIV-1-infected persons (p =.342). In contrast, among patients with CD4+ cell counts >500 x 106/L, none of 26 HIV-2-infected persons had detectable RT activity compared with 13 (52%) of 25 HIV-1-infected persons (p <.001). Our data suggest that unlike HIV-1 infection, HIV-2 infections with CD4+ cell counts >500 x 106/L are associated with a low level of viral replication, which may explain the longer clinical latency and lower transmissibility seen in HIV-2 infection.

Short-course oral zidovudine for prevention of mother-to-child transmission of HIV-1 in Abidjan, Côte d'Ivoire: a randomised trial.

BACKGROUND: In Africa, the risk of mother-to-child transmission of HIV-1 infection is high. Short-course perinatal oral zidovudine might decrease the rate of transmission. We assessed the safety and efficacy of such a regimen among HIV-1-seropositive breastfeeding women in Abidjan, Côte d'Ivoire. METHODS: From April, 1996, to February, 1998, all consenting, eligible HIV-1-seropositive pregnant women attending a public antenatal clinic in Abidjan were enrolled at 36 weeks' gestation and randomly assigned placebo or zidovudine (300 mg tablets), one tablet twice daily until the onset of labour, one tablet at onset of labour, and one tablet every 3 h until delivery. We used HIV-1-DNA PCR to test the infection status of babies at birth, 4 weeks, and 3 months. We stopped the study on Feb 18, 1998, when efficacy results were available from a study in Bangkok, Thailand, in which the same regimen was used in a non-breastfeeding population. FINDINGS: 280 women were enrolled (140 in each group). The median duration of the prenatal drug regimen was 27 days (range 1-80) and the median duration of labour was 7.5 h. Treatment was well tolerated with no withdrawals because of adverse events. All babies were breastfed. Among babies with known infection status at age 3 months, 30 (26.1%) of 115 babies in the placebo group and 19 (16.5%) of 115 in the zidovudine group were identified as HIV-1 infected. The estimated risk of HIV-1 transmission in the placebo and zidovudine groups were 21.7% and 12.2% (p=0.05) at 4 weeks, and 24.9% and 15.7% (p=0.07) at 3 months. Efficacy was 44% (95% CI -1 to 69) at age 4 weeks and 37% (-5 to 63) at 3 months. INTERPRETATION: Short-course oral zidovudine was safe, well tolerated, and decreased mother-to-child transmission of HIV-1 at age 3 months. Substantial efforts will be needed to ensure successful widespread implementation of such a regimen.

Lack of protection against HIV-1 infection among women with HIV-2 infection.

OBJECTIVE: To assess whether HIV-2 infection protects against HIV-1 infection by comparing the rate of HIV-1 seroconversion among HIV-negative and HIV-2-seropositive women followed in a cohort study in Abidjan, Côte d'Ivoire. DESIGN: Prospective cohort study METHODS: HIV seroconversion was assessed in 266 HIV-seronegative, 129 HIV-1-seropositive, and 127 HIV-2-seropositive women participating in a closed cohort study of mother-to-child transmission of HIV conducted during 1990-1994. Participants were seen every 6 months, and blood samples were obtained. All blood samples were screened for HIV antibodies by enzyme immunoassay (EIA) and confirmed by line immunoassay (LIA) and Western blot. Among women who were HIV-seronegative at enrolment, seroconversion was defined as new EIA-reactivity confirmed on LIA and Western blot. Among HIV-1- or HIV-2-seropositive women, seroconversion to dual reactivity was defined as new dual reactivity on the LIA that was confirmed by reactivity on both HIV-1- and HIV-2-monospecific EIA. RESULTS: Five HIV-seronegative women became HIV-1-seropositive [seroconversion rate, 1.1 per 100 person-years; 95% confidence interval (CI), 0.3-2.5), and none became HIV-2-seropositive. No HIV-1-seropositive women became HIV-1/2 dually reactive, whereas six HIV-2-seropositive women acquired HIV-1 seroreactivity and thus became HIV-1/2 dually reactive (seroconversion rate 2.9 per 100 person-years; 95% CI, 1.1-6.3). HIV-2-seropositive women were more likely to acquire HIV-1 seroreactivity than were HIV-seronegative women (rate ratio, 2.7; 95% CI, 0.7-11.2), but this difference was not statistically significant (P>0.15). CONCLUSION: HIV-2 infection does not appear to protect against HIV-1 infection.

Predominance of human immunodeficiency virus type 2 subtype B in Abidjan, Ivory Coast.

We analyzed the genetic variability and phylogenetic relationships among 28 HIV-2 strains collected from patients enrolled in an HIV epidemiologic study in Abidjan, Ivory Coast, during 1995-1996. Although both subtype A (n = 8; 29%) and subtype B (n = 20; 71%) were present in this sampling, the majority of infections were caused by subtype B viruses. These findings contrasted with the reported predominance of HIV-2 subtype A in other African countries. The broad genetic diversity identified among protease gene sequences for HIV-2 subtype A (6%; range 3-15%) and subtype B (7%; range, 2-12%), and their presence in Abidjan during the 1980s, document a long coexistence of two viral subtypes in Ivory Coast. Our data indicate that viruses of subtypes A and B have contributed to the HIV-2 epidemic in Ivory Coast.

Genetic analysis of human immunodeficiency virus in Abidjan, Ivory Coast reveals predominance of HIV type 1 subtype A and introduction of subtype G.

To better understand the molecular epidemiology of HIV genetic diversity in Abidjan, Ivory Coast, we performed a genetic analysis of 170 HIV-1-seropositive specimens representing newly diagnosed tuberculosis patients (n = 143) and women monitored in a mother-to-child transmission cohort study (n = 27). Preliminary screening with RFLP presumptively classified 162 (95.3%) of these as subtype A. The envelope region of 108 specimens was subtyped by sequence analysis: 102 (94.4%) were subtype A, 2 (1.9%) were subtype D, and 4 (3.7%) were subtype G. Subtyping gag and env regions of the genome suggested that five of the six nonsubtype A isolates exhibited a potentially mosaic structure. A comparative phylogenetic analysis of HIV-1 subtype A C2V3 from 27 Ivory Coast and 21 Ugandan sequences revealed a striking clustering among Ivory Coast variants, and an independent segregation from Ugandan subtype A. Despite independent clustering with other subtype A specimens, limited variability of the V3 loop apex was observed; the globally predominant V3 motif, GPGQ, represented 90.1% of the HIV-1 strains. This study demonstrates that clade A is the predominant HIV-1 subtype in HIV-seropositive individuals in Abidjan, Ivory Coast and that these strains are phylogenetically distinct from other subtype A strains observed in East Africa.

Evidence of Nef truncation in human immunodeficiency virus type 2 infection.

Human immunodeficiency virus (HIV)-2 differs from HIV-1 in its relative lower transmissibility and pathogenicity. To understand the virologic basis of these differences, the nef gene from HIV-2-seropositive persons was analyzed because of its importance for disease progression in the genetically related simian immunodeficiency virus (SIV[MAC]). Proviral nef sequences from 60 HIV-2-infected persons were amplified from peripheral blood lymphocytes, and nef open-reading frames were screened by a transcription and translation assay for the presence of full-length (32- to 36-kDa) or truncated (<32 kDa) Nef proteins. Overall, 6 (10%) of 60 persons had truncated Nef proteins; of these, 5 were among the 36 asymptomatic subjects (13.9%) and only 1 was among the 24 symptomatic subjects (4.2%) (P =.23). The results of this study document the presence of defective nef genes in HIV-2 infections with a prevalence higher than that previously seen in HIV-1-infected cohorts of long-term nonprogressors or patients with AIDS.

Late postnatal mother-to-child transmission of HIV-1 in Abidjan, Côte d'Ivoire.

BACKGROUND: HIV-1 can be transmitted from an infected mother to her infant through breastfeeding, although the precise risk of transmission by this route is unknown. A long-term follow-up of children born to HIV-infected women in Abidjan, Côte d'Ivoire, has enabled us to estimate this risk. METHODS: Children born to 138 HIV-1-seropositive women, 132 HIV-2-seropositive women, 69 women seroreactive to both HIV-1 and HIV-2, and 274 HIV-seronegative women were enrolled at birth and followed up for as long as 48 months. All children were breastfed (median duration 20 months). Blood samples for either or both HIV PCR and HIV serology were obtained at 1, 2, and 3 months of age, and every 3 months thereafter. Early HIV infection was defined as a positive HIV-1 PCR result obtained in the first 6 months of life. Late postnatal transmission was diagnosed when a child had a negative PCR at 3 or 6 months of age, followed by either or both a positive HIV-1 PCR at 9 months or older, or persistently positive HIV-1 serology at 15 months or older. FINDINGS: 82 children born to HIV-1-seropositive mothers and 57 children born to mothers seropositive for both HIV-1 and HIV-2 had PCR results for samples taken within the first 6 months. By 6 months of age, 23 (28%; 95% CI 19-39) of the 82 children born to HIV-1-seropositive mothers and ten (18%; 95% CI 9-30) of the 57 children born to dually seropositive mothers were HIV-1 infected. Among children whose PCR results were negative at or before age 6 months, and who were followed up beyond 6 months, an additional four (9%) of the 45 children born to HIV-1-seropositive mothers and two (5%) of the 39 children born to dually seropositive mothers became HIV infected. The estimated rates of late postnatal transmission, with account taken of loss to follow-up and the observed pattern of weaning, were 12% (95% CI 3-23) and 6% (0-14), respectively. One of the five children whose mothers seroconverted from HIV-negative to HIV-1, and one of seven children whose mothers seroconverted from HIV-2 to dual reactivity, became HIV-1 positive. No case of late postnatal transmission occurred in children born to HIV-2-positive or persistently HIV-negative mothers. INTERPRETATION: Breastfed children born to mothers seropositive for HIV-1 alone or seropositive for HIV-1 and HIV-2 in Abidjan are at substantial risk of late postnatal transmission. Early cessation of breastfeeding at 6 months of age should be assessed as a possible intervention to reduce postnatal transmission of HIV.

Prevention of mother-to-child transmission of HIV-1 in Africa.

PIP: With the prevalence of HIV among pregnant women higher than 35% in some parts of sub-Saharan Africa, the number of HIV-infected children will continue to grow. It is estimated that almost 70% of the approximately 500,000 children who became infected with HIV in 1995 were born in sub-Saharan Africa. An effective intervention to prevent the vertical transmission of HIV is therefore most urgently needed in Africa. Following the release of the results of the AIDS Clinical Trials Group (ACTG) 076 study, the routine use of zidovudine (AZT) among HIV-infected pregnant women in the US and Europe has resulted in a significant reduction in the rate of mother-to-child vertical HIV transmission. However, most women in Africa will not benefit from these advances in the immediate future due to inadequate prenatal health care, the unavailability of prenatal HIV testing, and the high cost and complexity of the recommended regimen. Researchers need to build upon the findings of developed countries to identify feasible, effective, and implementable interventions to reduce the vertical transmission of HIV as well as to prevent HIV infection among women and to protect the health of HIV-infected women in Africa. Rates and timing of vertical HIV transmission, risk factors associated with vertical HIV transmission, and prevention interventions are discussed.^ieng

The epidemic of HIV/AIDS in Abidjan, Côte d'Ivoire: a review of data collected by Projet RETRO-CI from 1987 to 1993.

We present a review of epidemiologic data collected by Projet RETRO-CI between 1987 and 1993 on trends in human immunodeficiency virus type 1 (HIV-1) and HIV-2 infections and on cases of AIDS in Abidjan, Côte d'Ivoire. Overall rates of HIV infection in pregnant women had already reached 10% in 1987, and have increased only modestly since then. In contrast, in 1992-1993, rates in men with sexually transmitted diseases and in female commercial sex workers reached 27 and 86%, respectively. The increases in infection rates have been largely due to transmission of HIV-1, whereas rates of HIV-2 have remained stable or have declined. Among persons with tuberculosis and hospitalized patients, rates of 46-71% have been reached, increases in recent years again being largely attributable to HIV-1. Among the 15,245 AIDS cases reported by Projet RETRO-CI, a steady decline in the male:female sex ratio has occurred over time, from 4.8:1 in 1988 to 1.9:1 in 1993. It is likely that AIDS cases were initially concentrated among a core group of female commercial sex workers and their male clients. A substantial proportion of sex workers and their clients originate from neighboring countries, and migration is likely to have contributed to the spread of HIV infection in West Africa. Including HIV-associated pulmonary tuberculosis as an AIDS-defining illness increased AIDS cases reported by Projet RETRO-CI by 13% in 1993. Despite a need for interventional research, careful description of the evolution of HIV/AIDS in this region remains essential.

Prospective comparison of mother-to-child transmission of HIV-1 and HIV-2 in Abidjan, Ivory Coast.

OBJECTIVE: To compare mother-to-child transmission of human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2, respectively) and to assess the impact of maternal HIV-1 and HIV-2 infections on child survival. DESIGN: Prospective cohort study. SETTING: Maternal and child health center in a lower socioeconomic class district of Abidjan, Ivory Coast. PARTICIPANTS: A total of 18,099 women delivering between 1990 and 1992 were tested for HIV-1 and HIV-2 antibodies. A cohort of 613 pregnant women and their infants was followed prospectively (138 women reactive to HIV-1, 132 reactive to HIV-2, 69 reactive to both viruses, and 274 HIV-seronegative). MAIN OUTCOME MEASURES: Rates of perinatal transmission for HIV-1, HIV-2, and both viruses, determined from results of serological and polymerase chain reaction tests on children; survival of infants born to HIV-1-positive, HIV-2-positive, dually reactive, and HIV-seronegative women. RESULTS: Of the 18,099 women tested, 9.4% were reactive to HIV-1 alone, 1.6% to HIV-2 alone, and 1.0% to both viruses. The rate of perinatal transmission of HIV-1 was 24.7% (95% confidence interval [CI], 15.8% to 33.7%), compared with 1.2% (95% CI, 0.0% to 3.5%) for HIV-2 (relative risk, 21.3; 95% CI, 2.9 to 154.3). Overall, 19.0% (95% CI, 9.0% to 29.0%) of infants of dually reactive women became infected; of the 11 children concerned, 10 were infected with HIV-1 and one with HIV-1 and HIV-2. Infants of HIV-seropositive mothers had a reduced survival; mortality rates were 15.1, 13.0, 6.5, and 3.4 deaths per 100 child-years, respectively, for children of HIV-1-positive, dually reactive, HIV-2-positive, and HIV-seronegative women. CONCLUSIONS: The rate of perinatal transmission of HIV-2 (1.2%) was much lower than the rate of perinatal transmission of HIV-1 (24.7%), and this was associated with more favorable survival for infants of HIV-2-infected mothers. Dually reactive women could transmit both viruses, although transmission usually involved HIV-1 only. Public health guidelines should incorporate advice that perinatal transmission of HIV-2 is rare.

The public health implications of AIDS research in Africa.

The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic has led to greatly increased international collaboration for medical research, mainly epidemiologic in nature, in Africa. Greater understanding of HIV/AIDS has resulted, and considerable training and technology transfer have occurred. However, analytic and descriptive research in countries heavily affected by AIDS has been slow to turn to assessment of interventions, and practical benefits to those countries' public health and policies have lagged behind scientific knowledge. This article considers the public health implications of selected HIV/AIDS research in sub-Saharan Africa and discusses opportunities for interventions and more applied research. Topics covered include HIV testing and its role, surveillance, control of sexually transmitted diseases, the vulnerability of youth and women, tuberculosis, HIV/AIDS care, and the inadequacy of resources currently committed to HIV/AIDS prevention and control in resource-poor countries. Research on HIV/AIDS in Africa has yielded crucial information but now should prioritize interventions and their evaluation. Specific goals that might limit the effects of the HIV/AIDS epidemic in resource-poor countries are achievable given vision, commitment, and resources.

Retrospective study of maternal HIV-1 and HIV-2 infections and child survival in Abidjan, Côte d'Ivoire.

OBJECTIVES: To compare the effects of maternal HIV-1 and HIV-2 infections on outcome of pregnancy, infant mortality, and child survival, and to measure serological concordance between mothers and children. DESIGN: Retrospective cohort study with cross sectional study of concordance for HIV antibodies. SETTING: Hospital, tuberculosis clinic, and maternal and child health centre in Abidjan, Côte d'Ivoire, west Africa. SUBJECTS: 986 women who had had a total of 2758 pregnancies since 1980. The last born children of 194 of these women. MAIN OUTCOME MEASURES: Pregnancy outcomes; mortality for all children born since 1980; and outcome for last born children. Serological concordance between mothers and last born children. RESULTS: Women with HIV-1 and HIV-2 infections had higher rates of spontaneous abortion and stillbirth than uninfected women (86/769 in HIV-1 positive women, 48/421 in HIV-2 positive, 31/234 in dually reactive, and 96/1131 in uninfected). Compared with children born to uninfected mothers (mortality 10.3%), greater proportions of children of HIV-1 positive (20.6%) and dually reactive (20.3%) mothers had died; mortality in children of HIV-2 infected women (13.1%) was not significantly increased. Infant mortalities for the last born children of HIV-1 positive, dually reactive, HIV-2 positive, and seronegative women were, respectively, 133, 82, 32, and 40 per 1000 live births. Nine of 77 last born children of HIV-1 positive mothers were concordantly seropositive compared with none of 21 children of HIV-2 infected mothers. CONCLUSIONS: Maternal HIV-2 infection has less influence on child survival than infection with HIV-1, probably because of a lower vertical transmission rate.

Epidemiology and transmission of HIV-2. Why there is no HIV-2 pandemic.

Although human immunodeficiency virus type 1 (HIV-1) and HIV-2 share modes of transmission, their epidemiologic characteristics differ and international spread of HIV-2 has been very limited. Recently, the prevalence of infection with HIV-1 but not HIV-2 has increased rapidly in different West African countries, where HIV-2 was probably present earlier. Among 19,701 women of reproductive age tested in Abidjan, Ivory Coast, between 1988 and 1992, the prevalence of HIV-1 infection increased from 5.0% to 9.2%, while that of HIV-2 declined from 2.6% to 1.5%. Differences in viral load may be responsible: reported results of virus culture and polymerase chain reaction assays suggest that at high CD4+ T-lymphocyte counts viral load is lower in HIV-2-infected than in HIV-1-infected persons; the efficacy of heterosexual and perinatal transmission of HIV-2 is less efficient than that of HIV-1 at this stage. At low (< 0.20 x 10(9)/L [< 200/microL]) CD4+ T-lymphocyte counts, virus isolation is equally successful for both viruses, and the efficacy of heterosexual transmission is similar. Differences in HIV-1 and HIV-2 natural history are reflected in differences in viral load, that for HIV-2 being lower until immunodeficiency is severe. Differences in viral load throughout most of the natural history of infection appear to correlate with lower transmissibility of HIV-2 than HIV-1, and are the likeliest explanation for their markedly different global epidemiology.

Immunological comparison of HIV-1-, HIV-2- and dually-reactive women delivering in Abidjan, Côte d'Ivoire.

OBJECTIVES: To compare the basic immunological changes induced by HIV-1 and HIV-2 infection and to assess the immune status of subjects serologically reactive to both HIV-1 and HIV-2 (dually-reactive). DESIGN: Immune parameters were studied cross-sectionally in women delivering in Abidjan, Côte d'Ivoire, West Africa, where HIV-1 and HIV-2 are endemic. In this area, a significant number of sera from infected individuals are reactive to both HIV-1 and HIV-2. SUBJECTS AND METHODS: Two hundred and twenty-eight women delivering in a major maternity clinic were screened for HIV-1 and HIV-2 using an enzyme-linked immunosorbent assay. Seropositivity was confirmed by Western blot. The immune parameters studied were CD4+ and CD8+ lymphocyte subsets, immunoglobulin (Ig) serum levels, neopterin and beta 2-microglobulin (beta 2M) serum levels. RESULTS: Similar but less pronounced immune changes were present in HIV-2-reactive subjects compared with HIV-1- and dually-reactive subjects. The observed differences between the HIV-seropositive groups could not be explained by differences in age or disease stage but paralleled differences in the frequency of persistent generalized lymphadenopathy (PGL). The intermediate immune profile of HIV-2-reactives (between seronegatives and HIV-1- and dually-reactives) was most clearly reflected by the number of CD8+ lymphocytes, the CD4:CD8 ratio and the IgG serum level. Median neopterin and beta 2M levels, though significantly increased in all HIV-seropositive groups, did not differ significantly between HIV-2-, HIV-1- and dually-reactives. CONCLUSIONS: HIV-2 infection is associated with typical HIV-related immunological changes. Immunologically, dually-reactives resemble HIV-1-reactives more closely than HIV-2-reactive subjects.

HIV-1 and HIV-2 infection in children in Abidjan, Côte d'Ivoire.

We conducted a study of 1,003 well and hospitalized children, birth to 5 years old, in Abidjan, Côte d'Ivoire, to determine the prevalence of HIV-1 and HIV-2 infection, evaluate risk factors for infection, and describe associated clinical characteristics. The overall seroprevalence was significantly higher for children in the hospital (10.8%) than for those attending the clinic (3.6%). HIV-1 was the predominant virus in both populations, comprising 87% (hospital) and 77% (clinic) of the seroreactive blood specimens. Ninety-two percent of seroreactive children of all ages had a mother who was HIV positive; 77% of seroreactive children greater than or equal to 15 months old had an HIV-infected mother. The remaining seropositive children had a history of receiving blood transfusions. Hospitalized children who were HIV-1 positive or dually seroreactive were more likely to have HIV-related clinical signs and symptoms than HIV-negative children. These findings suggest that HIV infection is an important cause of morbidity for children in Abidjan and that maternal infection is the primary risk factor for both HIV-1 and HIV-2 infection in children. Further evaluation and attention should be given to transmission, clinical characteristics, and the impact of HIV infection in children in West Africa, where both HIV-1 and HIV-2 are present.