[Show abstract][Hide abstract] ABSTRACT: In a population-based study in northern Malawi we investigated HIV-1 subtype C gag and env gene sequences associated with long-term survival. DNA samples were available from 31 individuals surviving between population surveys carried out in the 1980s and 1990s. Most survivors with paired sequences dating from the 1980s and the 1990s had a three codon deletion in the gag p17 region of the sequence retrieved from the sample collected in the 1990s that was not present in the sequence from the same individual dating from the 1980s. This deletion was also not present in any other 1980s sequences from Malawi, but was common in samples collected in Malawi in the 1990s. The deletion is equivalent to the loss of three amino acids in the D helix region of the gag protein, and may be associated with longer survival and onward transmission.
AIDS Research and Human Retroviruses 03/2006; 22(2):195-201. DOI:10.1089/aid.2006.22.195 · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human immunodeficiency virus type 1 (HIV-1) subtype C is responsible for more than 55% of HIV-1 infections worldwide. When this subtype first emerged is unknown. We have analyzed all available gag (p17 and p24) and env (C2-V3) subtype C sequences with known sampling dates, which ranged from 1983 to 2000. The majority of these sequences come from the Karonga District in Malawi and include some of the earliest known subtype C sequences. Linear regression analyses of sequence divergence estimates (with four different approaches) were plotted against sample year to estimate the year in which there was zero divergence from the reconstructed ancestral sequence. Here we suggest that the most recent common ancestor of subtype C appeared in the mid- to late 1960s. Sensitivity analyses, by which possible biases due to oversampling from one district were explored, gave very similar estimates.
Journal of Virology 11/2004; 78(19):10501-6. DOI:10.1128/JVI.78.19.10501-10506.2004 · 4.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Six divergent HIV-1 partial env and gag genome sequences have been characterized in five subjects in Malawi, from whom blood spot samples were collected between 1982 and 1989, at the time that the AIDS epidemic there was starting. These sequences could not be classified with any of the recognized subtypes or circulating recombinant forms of HIV-1. They showed no consistent and/or supported associations with other subtypes by either env or gag gene phylogenetic analysis. Their genetic distances from defined subtypes suggest that they may be diverse subsubtype C viruses or, alternatively, that they may have mosaic genomes. Bootscanning analyses are consistent with their being mosaic viruses. These sequences highlight early HIV-1 diversity in a population otherwise dominated by subtype C.
AIDS Research and Human Retroviruses 06/2003; 19(5):441-5. DOI:10.1089/088922203765551782 · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have tracked the early years of the evolution of the human immunodeficiency virus type 1 (HIV-1) epidemic in a rural district of central east Africa from the first documented introductions of subtypes A, D, and C to the present predominance of subtype C. The earliest subtype C sequences ever reported are described. Blood samples were collected on filter papers from 1981 to 1984 and from 1987 to 1989 from more than 44,000 individuals living in two areas of Karonga District, Malawi. These samples included HIV-1-positive samples from 200 people. In 1982 to 1984, HIV-1 subtypes A, C, and D were all present, though in small numbers. By 1987 to 1989, 152 (90%) of a total of 168 sequences were subtype C and AC, AD, and DC recombinants had emerged. Four of the subtype C sequences from 1983 to 1984 were closely related and were found at the base of a large cluster of low diversity that by the late 1980s accounted for 40% of C sequences. The other two early C sequences fell into a separate and more diverse cluster. Three other clusters containing sequences from the late 1980s were identified. Each cluster contained at least one sample from a person who had recently arrived in the district. From 18 HIV-1-positive spouse pairs, 12 very closely related pairs of sequences were identified. We conclude that there were multiple introductions of HIV-1 with limited spread, followed by explosive growth of a subtype C cluster, probably arising from a single introduction in or before 1983.
Journal of Virology 01/2003; 76(24):12890-9. DOI:10.1128/JVI.76.24.12890-12899.2002 · 4.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To measure the effect of HIV on survival in rural Africa.
A retrospective cohort study with more than 10 years follow-up.
Individuals with known HIV status in the 1980s were identified from previous population surveys in Karonga District, northern Malawi. Follow-up studies were conducted in 1998-2000 to trace 197 HIV-positive and 396 age-sex-matched HIV-negative individuals and their spouses.
Information was obtained on all but 11 index individuals. Half (302) were found and the others were reported to have died (161) or to be alive outside the district (119). Ten year survival was 36% in the HIV-positive cohort and 90% in the initially HIV-negative cohort. The death rate was 93.3 per 1000 person-years in the HIV-positive individuals, and 11.3 in the initially HIV-negative individuals. Survival time since the initial test in HIV-positive individuals decreased with age, but relative survival, compared with HIV-negative individuals, was similar across age groups. The effect of HIV on survival was similar in men and women. Spouses of HIV-positive individuals had four times the mortality rate, and among survivors, four times the HIV prevalence, of spouses of initially HIV-negative individuals.
HIV-infected individuals had very high mortality rates, but one-third were still alive at 10 years. This is consistent with median survival from seroconversion being similar to that found in developed countries before antiretroviral therapy. Mortality rates in HIV-positive individuals increased with age, but relative mortality changed little with age.
AIDS 08/2002; 16(11):1545-50. DOI:10.1097/00002030-200207260-00012 · 6.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the prevalence and sociodemographic risk factors for HIV infection, during the early stages of the epidemic, in a rural area of northern Malawi.
As part of a community-based study of mycobacteria, socioeconomic data and HIV results are available on approximately 30,000 individuals from random population samples in 1981-1984 and 1987-1989 from a rural area of Malawi. These have been analysed to characterize the early stages of the HIV epidemic.
The earliest HIV-positive specimens were collected in 1982. HIV prevalence in individuals aged 15-49 years was 0.1% in the early 1980s and 2.0% in the late 1980s. In the early 1980s, eight out of 11 HIV-positive individuals were new immigrants to the district or had recently returned there. In the late 1980s, immigration and having spent time outside the district continued to be major risk factors for HIV. HIV infection was more common in those with occupations other than subsistence farming, in those with more schooling, and in those in the best housing. The association with schooling was seen at all ages for both men and women.
Immigration and travel were important in the repeated introduction and establishment of the HIV epidemic. The association with schooling is similar to that found elsewhere in Africa.
AIDS 11/2001; 15(15):2025-9. DOI:10.1097/00002030-200110190-00016 · 6.56 Impact Factor